Blood pressure effects of acute intravenous renin or oral angiotensin converting enzyme inhibition in essential hypertension Renin predicts diastolic blood pressure response to nonpharmacologic and pharmacologic therapy. Renin status does not predict the anti-hypertensive response to angiotensin-converting enzyme inhibition in African–Americans A comparison of outcomes with angiotensin-converting--enzyme inhibitors and diuretics for hypertension in the elderly. Blood Pressure Lowering in Essential Hypertension With an Oral Renin Inhibitor, Aliskiren Pharmacogenetic Association of the Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism on Blood Pressure and Cardiovascular Risk in Relation to Antihypertensive Treatment: The Genetics of Hypertension-Associated Treatment (GenHAT) Study Differential effects of renin–angiotensin–aldosterone system inhibition, sympathoinhibition and diuretic therapy on endothelial function and blood pressure in obesity-related hypertension: a double-blind, placebo-controlled cross-over trial Effect of candesartan and lisinopril alone and in combination on blood pressure and microalbuminuria Comparative effects of chronic ACE inhibition and AT1 receptor blocked losartan on cardiac hypertrophy and renal function in hypertensive patients Clinical variables, not RAAS polymorphisms, predict blood pressure response to ACE inhibitors in Sardinians. Comparison of blood pressure and angiotensin responses to the renin inhibitor Ro 42-5892 and the angiotensin converting enzyme inhibitor enalapril in essential hypertension Combination of half doses of angiotensin type 1 receptor antagonist and angiotensin-converting enzyme inhibitor in diabetic nephropathy. Prolonged Duration of Blood Pressure Response to Enalkiren, the Novel Dipeptide Renin Inhibitor, in Essential Hypertension Renal vascular responses to renin inhibition with zankiren in men Plasma renin predicts success of antihypertensive drug withdrawal. Angiotensin converting enzyme gene polymorphism predicts blood pressure response to angiotensin II receptor type 1 antagonist treatment in hypertensive patients Angiotensin-converting enzyme inhibition in mild hypertension with concomitant diseases and therapies: an efficacy, safety, and compatibility study of novel design, the Perindopril Therapeutic Safety Study.
Objective To assess the participation of the renin-angiotensin system in the blood pressure regulation of essential hypertensive patients through acute specific renin inhibition Design and methods Fifty-three consecutive untreated hypertensive patients ( mean ± SD age 55 ± 10 years , 42 male ) were investigated on their usual sodium diet in a 3-h protocol . The first 11 patients did not receive any drug , the following 20 patients ingested a single oral dose of captopril ( 1 mg/kg ) and the last 22 patients received a renin inhibitor infusion ( remikiren ; 1 mg/kg over 60min ) Results The maximum diastolic blood pressure fall was comparable in the two treated groups . Diastolic blood pressure changes analysed as area under the curve were similar for both drugs ( overall F1,40= 1.26 , P=0.27 ) . Even though the baseline renin levels were within the narrow range 5–80 pg/ml , the diastolic blood pressure fall analysed as area under the curve from time 32 min to time 60min was significantly correlated with the baseline active renin level in both groups ( remikiren r = 0.44 , P < 0.05 ; captopril r = 0.47 , P < 0.05 ) . The plasma active renin levels were significantly increased at 30 , 90 and 120min in both groups , and the maximum active renin levels were significantly correlated with the baseline active renin level ( remikiren r = 0.62 , P < 0.01 ; captopril r = 0.66 , P<0.01 ) . The plasma prorenin levels did not change Conclusions This study suggests that acute renin inhibition and acute angiotensin converting enzyme inhibition similarly decrease the blood pressure and increase the plasma active renin levels . Acute blockade of the renin-angiotensin system at its initial step by a renin inhibitor can therefore be used to investigate the renin dependence of the blood pressure in essential OBJECTIVE Plasma renin activity was measured at baseline and 6 months in a trial of nonpharmacologic therapy of mild hypertension to determine whether plasma renin activity predicts the diastolic blood pressure ( DBP ) response to nonpharmacologic therapy . DESIGN , SETTING , AND PARTICIPANTS R and omized controlled trial of volunteers from the general community with mild hypertension ( DBP between 90 and 100 mm Hg ) , off all antihypertensive therapy at baseline , treated in special research clinics ( n = 593 ) . INTERVENTIONS Subjects were r and omly assigned to usual , weight loss , or low sodium/high potassium diet and then r and omly assigned to receive placebo , chlorthalidone , or atenolol . MAIN OUTCOME MEASURES Renin was analyzed as plasma renin activity and as a renin index ( logarithm of 24-hour urinary sodium excretion times logarithm of plasma renin activity ) ( 593 patients at baseline and 6 months ) to correct for varied sodium intakes . The DBP was measured using the r and om zero device . RESULTS Change in DBP at 6 months could be predicted from baseline plasma renin activity or renin index . The DBP was decreased after 6 months of therapy by 2 mm Hg for each unit increase in baseline plasma renin activity and by 0.16 mm Hg for each unit increase in baseline renin index . Patients in the highest renin index quartile had a greater DBP response to atenolol therapy , and patients in the lowest renin index quartile had a greater DBP response to chlorthalidone therapy . Weight loss diet achieved a greater reduction in DBP in patients with higher baseline renin index and had an additive effect on DBP response in both of the drug groups . Patients on a weight loss diet receiving placebo in the highest baseline renin index quartile had a reduction in DBP of 12.4 mm Hg , compared with 4.4 mm Hg in the lowest baseline renin index quartile ( P = .009 ) . A low sodium/high potassium diet had a lesser effect than a weight loss diet on pharmacologic therapy . As with the weight loss diet , patients on a low sodium/high potassium diet in the highest baseline renin index quartile had a greater reduction in DBP than patients in the lowest baseline renin index quartile . CONCLUSIONS These data suggest a significant relationship between baseline levels of plasma renin index and the likelihood of success of nonpharmacologic treatment of hypertension The angiotensin-converting enzyme ( ACE ) inhibitor tr and olapril , a non-sulfhydryl prodrug which is hydrolysed into tr and olaprilat , was studied in 322 hypertensives of African – American descent using a double-blind , r and omised , placebo-controlled , parallel study design . Following 6 weeks of double-blind treatment with placebo or 0.25 to 16 mg/day tr and olapril , an analysis of drug effect on trough blood pressure ( BP ) stratified by age , gender , weight , pre-treatment plasma renin activity , and tr and olaprilat concentration was performed . Two mg was the lowest effective tr and olapril dose , whereas doses above 4 mg did not significantly reduce trough BP . Reduction in BP did not correlate with trough plasma tr and olaprilat concentration . Pre-treatment plasma renin activity was not a reliable indicator of antihypertensive response , as similar reductions in BP occurred even in patients with the lowest renin levels . There were no observable differences based on age , gender or measurements of the renin-angiotensin- aldosterone axis . In conclusion , neither age , gender or plasma renin activity influenced anti-hypertensive response to angiotensin-converting enzyme inhibition in African – BACKGROUND Treatment of hypertension with diuretics , beta-blockers , or both leads to improved outcomes . It has been postulated that agents that inhibit the renin-angiotensin system confer benefit beyond the reduction of blood pressure alone . We compared the outcomes in older subjects with hypertension who were treated with angiotensin-converting-enzyme ( ACE ) inhibitors with the outcomes in those treated with diuretic agents . METHODS We conducted a prospect i ve , r and omized , open-label study with blinded assessment of end points in 6083 subjects with hypertension who were 65 to 84 years of age and received health care at 1594 family practice s. Subjects were followed for a median of 4.1 years , and the total numbers of cardiovascular events in the two treatment groups were compared with the use of multivariate proportional-hazards models . RESULTS At base line , the treatment groups were well matched in terms of age , sex , and blood pressure . By the end of the study , blood pressure had decreased to a similar extent in both groups ( a decrease of 26/12 mm Hg ) . There were 695 cardiovascular events or deaths from any cause in the ACE-inhibitor group ( 56.1 per 1000 patient-years ) and 736 cardiovascular events or deaths from any cause in the diuretic group ( 59.8 per 1000 patient-years ; the hazard ratio for a cardiovascular event or death with ACE-inhibitor treatment was 0.89 [ 95 percent confidence interval , 0.79 to 1.00 ] ; P=0.05 ) . Among male subjects , the hazard ratio was 0.83 ( 95 percent confidence interval , 0.71 to 0.97 ; P=0.02 ) ; among female subjects , the hazard ratio was 1.00 ( 95 percent confidence interval , 0.83 to 1.21 ; P=0.98 ) ; the P value for the interaction between sex and treatment-group assignment was 0.15 . The rates of nonfatal cardiovascular events and myocardial infa rct ions decreased with ACE-inhibitor treatment , whereas a similar number of strokes occurred in each group ( although there were more fatal strokes in the ACE-inhibitor group ) . CONCLUSIONS Initiation of antihypertensive treatment involving ACE inhibitors in older subjects , particularly men , appears to lead to better outcomes than treatment with diuretic agents , despite similar reductions of blood pressure Abstract —Inhibition of the first and rate-limiting step of the renin-angiotensin system has long been an elusive therapeutic goal . Aliskiren , the first known representative of a new class of completely nonpeptide , orally active , renin inhibitors , has been shown to inhibit the production of angiotensin I and II in healthy volunteers and to reduce blood pressure ( BP ) in sodium-depleted marmosets . The aim of this r and omized , double-blind , active comparator trial study was to assess the BP-lowering efficacy and safety of aliskiren .  Two hundred twenty-six patients , 21 to 70 years of age , with mild to moderate hypertension , were r and omly assigned to receive 37.5 mg , 75 mg , 150 mg , or 300 mg aliskiren or 100 mg losartan daily for 4 weeks . Dose-dependent reductions in daytime ambulatory systolic pressure ( mean change , mm Hg [ SD of change ] ; −0.4 [ 11.7 ] , −5.3 [ 11.3 ] , −8.0 [ 11.0 ] , and −11.0 [ 11.0 ] , P = 0.0002 ) and in plasma renin activity ( median change % [ interquartile range ] ; −55 [ −64 , −11 ] , −60 [ −82 , −46 ] , −77 [ −86 , −72 ] , and −83 [ −92 , −71 ] , P = 0.0008 ) were observed with 37.5 , 75 , 150 , and 300 mg aliskiren . The change in daytime systolic pressure with 100 mg losartan ( −10.9 [ 13.8 ] ) was not significantly different from the changes seen with 75 , 150 , and 300 mg aliskiren . Aliskiren was well tolerated at all doses studied . This study demonstrates that aliskiren , through inhibition of renin , is an effective and safe orally active BP-lowering agent . Whether renin inhibition results in protection from heart attack , stroke , and nephropathy , similar to angiotensin-converting enzyme inhibition and angiotensin receptor blockade , needs to be research ed Background —Previous studies have reported that blood pressure response to antihypertensive medications is influenced by genetic variation in the renin-angiotensin-aldosterone system , but no clinical trails have tested whether the ACE insertion/deletion ( I/D ) polymorphism modifies the association between the type of medication and multiple cardiovascular and renal phenotypes . Methods and Results —We used a double-blind , active-controlled r and omized trial of antihypertensive treatment that included hypertensives ≥55 years of age with ≥1 risk factor for cardiovascular disease . ACE I/D genotypes were determined in 37 939 participants r and omized to chlorthalidone , amlodipine , lisinopril , or doxazosin treatments and followed up for 4 to 8 years . Primary outcomes included fatal coronary heart disease ( CHD ) and /or nonfatal myocardial infa rct ion . Secondary outcomes included stroke , all-cause mortality , combined CHD , and combined cardiovascular disease .  Fatal and nonfatal CHD occurred in 3096 individuals during follow-up . The hazard rates for fatal and nonfatal CHD and the secondary outcomes were similar across antihypertensive treatments . ACE I/D genotype group was not associated with fatal and nonfatal CHD ( relative risk of DD versus ID and II , 0.99 ; 95 % CI , 0.91 to 1.07 ) or any secondary outcome . The 6-year hazard rate for fatal and nonfatal CHD in the DD genotype group was not statistically different from the ID and II genotype group by type of treatment . No secondary outcome measure was statistically different across antihypertensive treatment and ACE I/D genotype strata . Conclusions —ACE I/D genotype group was not a predictor of CHD , nor did it modify the response to antihypertensive treatment . We conclude that the ACE I/D polymorphism is not a useful marker to predict antihypertensive treatment response Objectives : The objective of this study is to determine the effects of renin -- angiotensin -- aldosterone system inhibition , sympathoinhibition and diuretic therapy on endothelial function and blood pressure in obesity-related hypertension . Methods : A r and omized , four-way , double-blind , crossover study in 31 adults with previously untreated obesity-related hypertension , in which the effects of 8 weeks ’ inhibition of the renin -- angiotensin -- aldosterone system ( using aliskiren 300 mg ) , sympathoinhibition ( using moxonidine 0.4 mg ) , diuretic therapy ( using hydrochlorothiazide 25 mg ) or placebo on flow-mediated dilation and 24-h blood pressure were compared . Results : The median flow-mediated dilation during placebo was 4.0 % [ interquartile range ( IQR ) 2.9–5.5 % ] and was increased by aliskiren [ 0.81 % , 95 % confidence interval ( CI ) 0.02–1.79 ] , but not by moxonidine ( 0.20 % , 95 % CI −0.46 to 1.03 ) or hydrochlorothiazide ( 0.39 % , 95%CI −0.31%–1.26 % ) . Similarly , compared with placebo  , mean 24-h blood pressure was most reduced by aliskiren ( −9.8/−6.3 mmHg ) and to a lesser degree by hydrochlorothiazide ( −5.9/−2.6 mmHg ) . Moxonidine did not significantly affect blood pressure despite reduction of muscle sympathetic nerve activity . Insulin sensitivity deteriorated during hydrochlorothiazide treatment and was unaffected by aliskiren or moxonidine . Unlike aliskiren and moxonidine , hydrochlorothiazide  reduced urinary 8-iso-prostagl and in F2&agr;-VI , a marker of oxidative stress . Vascular stiffness , systemic inflammation , leptin , adiponectin and other oxidative stress markers ( plasma malondialdehyde , myeloperoxidase activity and urinary 8-hydroxydeoxyguanosine ) were unaffected by treatment . Conclusion : Renin inhibition , but not sympathoinhibition or diuretic therapy , improves endothelial function and results in larger reductions of 24-h , office , and central blood pressure in obesity-related hypertension . This adds weight to the hypothesis that inhibition of the renin -- angiotensin -- aldosterone system is an effective first step in the treatment of obesity-related hypertension Background Angiotensin-converting enzyme ( ACE ) inhibitors and angiotensin receptor blocking drugs ( ARB ) block the effect of angiotensin II by different mechanisms . It has been suggested that combined therapy may be more effective at reducing blood pressure ( BP ) than higher doses of either drug . Methods Twenty-three elderly patients with systolic hypertension completed a double-blind crossover study comparing placebo , c and esartan ( C ) 16 mg , C32 mg , lisinopril ( L ) 20 mg , L40 mg and C16 mg + L20 mg . Treatment periods were one month and ambulatory BP measurements were performed at the end of each period . The effects on albumin excretion in eight patients with microalbuminuria  were determined . Results All treatments lowered BP . The falls in systolic and diastolic BP with C16 , C32 , L20 and L40 were similar . Plasma renin rose to a similar extent . A plateau effect was reached with C16 and L20 . Systolic BP on the combination of C16 + L20 was lower than on each monotherapy ( C16 , 3.8 mmHg [ p=0.002 ] ; C32 , 6.4 [ 0.0003 ] ; L20 , 2.9 [ 0.05 ] ; L40 , 3.3 [ 0.003 ] ) . The additional fall in BP with the combination appeared to be due to recruitment of non-responders , rather than to an additive effect in most patients . All treatments reduced microalbuminuria to a similar extent . The combination was well tolerated and there was no deterioration in renal function . Conclusion When patients are on a plateau dose of an ACE inhibitor or an ARB , addition of the other drug class has a small but significant incremental effect on BP in the overall group . However , some patients respond better to one drug class than to the other and this may explain the results . This study lends no support to the use of these two drugs in combination to treat hypertension The present study describes the effects of losartan and the angiotensin-converting enzyme inhibitor enalapril on blood pressure , echocardiographically calculated left ventricular mass , renal function evaluated by glomerular filtration rate and quality of life . The renin-angiotensin-aldosterone system is of importance for cardiovascular growth . There is substantial experimental documentation in animals that the angiotensin II antagonist , losartan , decreases the cardiac hypertrophy response caused by elevated arterial pressure as well as intravascular volume overload . However , data in humans is scarce . This is a 3-year , r and omised , double-blind study with parallel group design in 50 patients with essential hypertension . The results show that both drugs reduced blood pressure equally effectively , and also left ventricular mass ( P < 0.001 ) . After 3 years of treatment glomerular filtration rate significantly increased with losartan ( P < 0.005 ) . Serum uric acid fell modestly although significantly , dose-dependent in losartan patients compared with an increase in enalapril patients . A fall in serum potassium from the pre- study period was observed in all patients . There was no difference between treatments in terms of patient satisfaction on quality of life . Both drugs have relatively similar hormonal and haemodynamic effect , with an excellent tolerability profile ; they appear to induce comparable blood pressure falls in hypertensive patients in particular , therapy based on specific Ang II blockade may offer advantages in high risk hypertensives if left ventricular hypertrophy is present . Both enalapril and losartan , in improving the renal function attenuating the intrarenal effects of angiotensin II , might be able to reverse the pathophysiology of essential hypertensive kidney disease , and should be first-choice drugs in the treatment of essential hypertension AIM No definite factors predict blood pressure response to angiotensin-converting enzyme-inhibitors . The aim of this study was to test the association of gene polymorphisms of the renin-angiotensin-aldosterone system with essential hypertension and anthropometric variables , intermediate phenotypes and gene polymorphisms with blood pressure after fosinopril in a genetically homogeneous cohort . METHODS A total of 630 essential hypertension patients , not previously treated or out of antihypertensive treatment for at least 6 months versus 219 normotensives ( genotype frequencies , chi(2 ) ) . A total of 191 patients were r and omly assigned to fosinopril 20 mg/day . Sample s for plasma renin activity and aldosterone , 24-h urinary sodium ( flame photometry ) were collected . Gene polymorphisms -- angiotensin-converting enzyme ( insertion/deletion ) , angiotensin II type 1-receptor ( A1166C ) , aldosterone synthase ( -344C/T ) and angiotensinogen (-6A/G)--were analyzed by st and ard techniques . The association of anthropometric variables , intermediate phenotypes and gene polymorphisms with blood pressure after 4 weeks therapy was tested by univariate analysis and analysis of covariance model ( Intercooled Stata SE 9.2 ) . RESULTS No genetic polymorphisms were associated with essential hypertension , blood pressure response and intermediate phenotypes ( p > 0.05 ) . Systolic blood pressure after therapy was associated with baseline systolic blood pressure , age and sex . CONCLUSIONS Our results confirm the difficulty in dissecting both essential hypertension and pharmacogenomics when analyzing the effect of single genes in complex multifactorial traits Objective : To compare the responses of angiotensin II ( Ang II ) and blood pressure to the renin inhibitor Ro 42 - 5892 and the angiotensin converting enzyme ( ACE ) inhibitor enalapril Subjects : Eight non-sodium-restricted patients with mild-to-moderate essential hypertension Design : A single-blind crossover study . Ro 42 - 5892 ( 600 mg orally , once a day ) and enalapril ( 20 mg orally , once a day ) were given for 8 days before detailed investigations were carried out . Methods : Ambulatory blood pressure was measured directly for 24 h by the Oxford technique on three occasions . Off-treatment and on day 8 of treatment with Ro 42 - 5892 and with enalapril .  Ang II was measured by radioimmunoassay after separation by high-performance liquid chromatography Results : Plasma renin activity and Ang II were lowered by 83 % [ 95 % confidence interval ( CD 61 - 105 ] and 68 % ( 95 % Cl 49 - 87 ) , respectively , 0.5 - 1 h after Ro 42 - 5892 , but after only 3h values had returned to baseline . Unlike this rapid and short-term suppression of Ang II , the maximal antihypertensive response to Ro 42 - 5892 ( fall in blood pressure 12.9/9.0 mmHg ) occurred only after 6h . Blood pressure returned to baseline after 8h . In response to enalapril , Ang II was maximally suppressed by 63 % ( 95 % Cl 32 - 94 ) after 2 h and by 83 % ( 95 % Cl 76 - 90 ) after 8 h. Despite early maximal Ang II suppression , the maximal antihypertensive response to enalapril occurred only after 12 h ( fall in blood pressure 25.3/16.3 mmHg ) . With this compound a significant antihypertensive effect was still present 24 h after dosing . Conclusions : Compared with enalapril at 20 mg once a day , repeated oral administration of a single dose of Ro 42 - 5892 at 600 mg caused only short-term suppression of Ang II and blood pressure . Suppression of Ang II and reduction in blood pressure were temporally dissociated , both with the ACE inhibitor and the renin inhibitor . This implies that the blood pressure lowering effect of these inhibitors is caused partly by Ang II suppression outside the BACKGROUND To investigate the renoprotective effect of combination therapy with an angiotensin I converting enzyme inhibitor and an angiotensin type I receptor blocker ( ARB ) on diabetic kidney disease , half doses of each monotherapy were given to type 2 diabetic patients with albuminuria . METHODS Urinary albumin index ( UAI ) and blood pressure ( BP ) were measured in a total of 27 out patients with type 2 diabetes mellitus receiving 10 mg imidapril or 8 mg c and esartan per day . Either agent was then substituted with a combination of 5 mg imidapril and 4 mg c and esartan . After 3 months of combination therapy , UAI and BP were measured . Changes in the parameters were assessed by paired t test . RESULTS Although BP was not significantly different prior to and at the end of combination therapy , log-transformed UAI was significantly reduced ( P = 0.003 ) from an initial UAI ( mean log-transformed UAI + /- SD ) of 79.4 (27.4 - 231)mg/g Cre to 52.5 (17.1 - 161)mg/g Cre at the end of combination therapy . The reduction was not associated with the initial UAI , initial BP , decrease in BP , pretreatment medication or other concomitant antihypertensive agents . CONCLUSIONS In patients with type 2 diabetes and nephropathy , dual blockade of the renin system with an angiotensin-converting enzyme inhibitor and angiotensin receptor blocker significantly reduces albuminuria and , thus , may be renoprotective even when the doses of the agents are reduced by one half The effects of sustained renin inhibition by repeated administration of enalkiren ( A- 64662 ) , the novel dipeptide renin inhibitor , were evaluated in a r and omized , double-blind , placebocontrolled , parallel-group study of 32 in patients ( eight per group ) with essential hypertension who were maintained on a diet containing 60 meq/day sodium . Three different dosage regimens of enalkiren were studied : 1 ) 1.2 mg/kg quotid . , 2 ) 03 mg/kg q.i.d . , and 3 ) 0.1 mg/kg q.i.d . Each patient received an intravenous infusion every 6 hours for 1 week . Placebo infusions were used to mimic the 4 times/day dosing schedule . Blood pressure was measured periodically via 24-hour automated monitoring equipment . Mean plasma renin activity in the patient groups ranged from 1.58 to 2.68 ng angiotensin I/ml/hr . Plasma renin activity was promptly suppressed in all groups receiving enalkiren . Prolonged duration of plasma renin activity suppression ( ≥24 hours ) was demonstrated after the administration of 1.2 mg/kg enalkiren . The 0 3 mg/kg q.i.d . and 1.2 mg/kg quotid . regimens produced statistically significant reductions ( p < 0.05 ) in systolic and diastolic blood pressures with clear evidence of persistent antihypertensive activity for 12 hours or more when compared with the placebo group . Despite relatively large reductions in mean systolic and diastolic blood pressure , mean pulse rates were essentially unchanged . The prolonged reduction in blood pressure  with enalkiren without evidence of tachyphylaxis after 1 week of treatment suggests that renin inhibitors may emerge as useful therapeutic agents for the treatment of hypertension Renin inhibition represents an alternative to angiotensin‐converting enzyme ( ACE ) inhibition for pharmacologic interruption of the renin‐angiotensin system . In addition to inhibiting the formation of angiotensin II , ACE inhibitors also inhibit the degradation of kinin and result in accumulation of powerful renal vasodilator prostagl and ins and bradykinin . We were therefore surprised by the large renal vasodilator response achieved with the renin inhibitor enalkiren , because substrate‐specific renin inhibitors reduce the formation of angiotensin II without affecting other vasodilator mechanisms . To determine whether previous findings were reflective of the renin inhibitor class , we studied 12 healthy men on a sodium‐restricted diet  , each of whom received two or three escalating oral doses of zankiren , a new agent . Plasma renin activity decreased with the smallest dose ( 5 mg ) , and this effect was sustained . The increase in renal plasma flow was clearly related to dose ( r = 0.86 , F = 9.67 ) , reaching a maximum of 134 ± 26 ml/min/1.73 m2 at 250 mg , the highest dose . Renin inhibition exerts a remarkable renal vasodilator action , perhaps reflecting the lipophilicity of the agents developed to date , an action that may have clinical implication s for the prevention of renal injury in patients at risk This study examined the relationship of plasma renin activity ( PRA ) to the likelihood of maintaining blood pressure control after discontinuation of antihypertensive medication . Patients whose blood pressure was previously treated and controlled in the Hypertension Detection and Follow-up Program were enrolled in the Dietary Intervention Study of Hypertension . After stratification by obesity , patients were r and omized to discontinue medication with no dietary intervention , sodium restriction , or weight reduction for the obese . Among 496 subjects in the Dietary Intervention Study of Hypertension , 75 were r and omly selected for PRA measurement at 4 months after intervention , and all had their blood pressure under control at that time . Patients were followed up for 56 weeks after r and omization . The endpoint was return to antihypertensive medication due to elevated diastolic blood pressure . Kaplan-Meier survival analysis showed that subjects with PRA < or = 53.3 ng/100 mL/h , the median level , had a lower cumulative success rate for remaining off antihypertensive drug than those with PRA above the median ( P = .046 ) . In Cox regression analysis controlling for 24-h urinary sodium level , baseline diastolic blood pressure , age , sex , race , obesity , and dietary intervention group , a unit decrease in log PRA was associated with a 2.78-fold increase in risk of returning to drug ( P = .006 ) ; this inverse relationship was independent of dietary intervention and change in diastolic blood pressure in the first 4 months before PRA was measured . The data indicate that patients with low PRA are less likely to maintain blood pressure control without drugs than patients with high PRA Objectives To determine whether polymorphisms in the renin – angiotensin system can predict blood pressure-lowering response to antihypertensive treatment ; more specifically , in response to treatment with irbesartan or atenolol . Design and methods Eighty-six patients with hypertension were r and omized to double-blind treatment with either the angiotensin II type 1 receptor antagonist irbesartan or the β1 adrenergic receptor blocker atenolol and followed for 3 months . We analysed angiotensinogen T174 M and M235 T , angiotensin converting enzyme ( ACE ) I/D and angiotensin II type 1 receptor A1166C polymorphisms and related them to blood pressure reduction . Results The mean reductions in blood pressure were similar for both treatments . In the irbesartan group , individuals homozygous for the ACE gene I allele showed a greater reduction in diastolic blood pressure , exceeding those with the D allele ( − 18 ± 11 SD versus − 7 ± 10 mmHg , P = 0.0096 ) . This was not the case during treatment  with atenolol  , and the interaction term between type of treatment and ACE II genotype was significant ( P = 0.0176 ) . The angiotensinogen and angiotensin II type 1 receptor polymorhisms were not related to the response to treatment . Conclusions ACE genotyping predicted the blood pressure-lowering response to antihypertensive treatment with irbesartan but not atenolol . Thus , specific genotypes might predict the response to specific antihypertensive treatment Despite a marked reduction in cardiovascular morbidity and mortality , treated hypertensive patients remain at increased risk of coronary artery disease and its complications compared with untreated normotensive subjects . Mild hypertension is often associated with other , usually chronic , diseases . The failure of first-line antihypertensive therapy to deal adequately with concomitant disease and associated therapy might account for the poor improvement in the cardiovascular prognosis . This possibility has been addressed in an ongoing trial of novel design , the Perindopril Therapeutic Safety Study , a multicenter , double-blind , r and omized and placebo-controlled trial to determine the safety , efficacy , and interaction of angiotensin-converting enzyme ( ACE ) inhibition with eight of the most common concomitant diseases and their therapies . A total of 480 male and female patients ( 60 per disease group ) aged 30 - 70 years , with a diastolic pressure of 90 - 104 mm Hg , were included after a 3-week placebo run-in if they satisfied st and ard criteria for any of the following : hyperlipidemia , type II diabetes , ischemic heart disease , cardiac arrhythmia , peripheral arterial disease , nephropathy with proteinuria , chronic obstructive lung disease , or rheumatoid arthritis . Of these , 460 patients have completed the 6-week double-blind phase ( comprising two assessment s , at 3 and 6 weeks ) , and are currently undergoing assessment s every 3 months over a 1-year follow-up period . The end points include the incidence of progression or improvement in concomitant disease , the incidence of positive or negative interaction between ACE inhibition and concomitant therapy , change in blood pressure , adverse biochemical and hemodynamic reactions , self-reported side effects , and quality of life indices . Interim results for the 6-week double blind phase will shortly be available . However , the desirability and feasibility of conducting a study according to this novel design have already been proved
There was a dose-dependent decrease in blood pressure for aliskiren 75 mg , 150 mg and 300 mg .
Aliskiren had no effect on blood pressure variability .
Due to very limited information available regarding change in heart rate and pulse pressure , it was not possible to meta-analyze these outcomes .Mortality and non-fatal serious adverse events were not increased .
AUTHORS ' CONCLUSIONS Compared to placebo , aliskiren lowered BP and this effect is dose-dependent .
This magnitude of BP lowering effect is similar to that for angiotensin-converting enzyme ( ACE ) inhibitors and angiotensin receptor blockers ( ARBs ) .
There is no difference in mortality , nonfatal serious adverse events or withdrawal due to adverse effects with short term aliskiren monotherapy .
BACKGROUND Hypertension is a chronic condition associated with an increased risk of mortality and morbidity .
Renin is the enzyme responsible for converting angiotensinogen to angiotensin I , which is then converted to angiotensin II .
Renin inhibitors are a new class of drugs that decrease blood pressure ( BP ) by preventing the formation of both angiotensin I and angiotensin II .
OBJECTIVES To quantify the dose-related BP lowering efficacy of renin inhibitors compared to placebo in the treatment of primary hypertension .
To determine the change in BP variability , pulse pressure , and heart rate and to evaluate adverse events ( mortality , non-fatal serious adverse events , total adverse events , withdrawal due to adverse effects and specific adverse events such as dry cough , diarrhoea and angioedema ) .