Antihypertensive Effect of Heimia Salicifolia
In order to evaluate the effects produced by the alkaloids of leaves from H. salicifolia on the blood pressure of rats, four alkaloids from H. salicifolia were isolated by column and thin layer chromatography. The alkaloids’ antihypertensive effects on angiotensin II-caused acute hypertension as well as their hypotensive effects on normotensive rats were studied. The alkaloid 3, the most abundant isolated alkaloid, turned out to be the most effective, while the other alkaloids showed a slight, non-significant vascular activity. Their mixture showed an additive effect, though slightly different from the alkaloid 3.
Emerging features of brain angiotensin receptors
In mammalian brain, angiotensin II AT1 and AT2 receptor subtypes are apparently expressed only in neurons and not in glia. AT1 and AT2 receptor subtypes are sometimes closely associated, but apparently expressed in different neurons. Brain AT1/AT2 interactions may occur in selective cases as inter-neuron cross talk. There are two AT1 isoforms in rodents. AT1A, which predominates, and AT1B. There are also important inter-species differences in receptor expression. Relative lack of amino acid conservation in the gerbil gAT1A receptor substantially decreases affinity for the AT1 antagonists. AT1 receptors are expressed in brain areas regulating autonomic and hormonal responses. AT1A receptors are heterogeneously regulated in a number of experimental conditions. In specific areas, AT1A receptors are not normally expressed, but are induced under influence of reproductive hormones in dopaminergic neurons. There are AT1 and AT2 receptors also in areas related to limbic, sensory and motor functions and their expression is developmentally regulated. A picture is emerging of widespread, neuronally localized, heterogeneously regulated, closely associated brain angiotensin receptor subtypes, modulating multiple functions including neuroendocrine and autonomic responses, stress, cerebrovascular flow, and perhaps brain maturation, neuronal plasticity, memory and behavior.
Role of phospholipase C and phospholipase A2 in the nitric oxide-independent vasodilator effect of bradykinin in the rat perfused heart.
The cytochrome P450-dependent component of the coronary vasodilator action of bradykinin which requires activation of K+ channels was examined in terms of the contribution of phospholipases in the rat Langendorff heart preparation. This component was isolated by inhibition of nitric oxide synthase with nitroarginine and cyclooxygenase with indomethacin, neither of which affects the coronary vasodilator action of bradykinin. However, nitroarginine elevated coronary perfusion pressure from approximately 40 to 130 mm Hg. The phospholipase C inhibitor, U73122 {1-(6-((17 beta-3-methoxyestra-1,3,5(10)-trien-17-yl) amino)hexyl)-1H-pyrrole-2,5-dione}, reduced coronary vasodilator responses to bradykinin by greater than 80%. U73122 also diminished the coronary vasodilator action of cromakalim which activates ATP-sensitive K+ channels. The maleimide moiety of U73122 that has the capacity to affect K+ channels inhibited cromakalim-induced coronary vasodilation, but did not affect that to bradykinin. Inhibition of diacylglycerol lipase with RHC 80267 {1,6-bis-(cyclohexyloximinocarbonylamino)-hexane} was without an overall effect on coronary vasodilator responses to bradykinin. The cytosolic phospholipase A2 inhibitor, AACOCF3 {arachidonyl trifluoromethyl ketone¿} decreased responses to bradykinin by up to 90% whereas inhibitors of the secretory form of phospholipase A2 oleyloxyethyl phosphorylcholine and ONO-RS-082 {2-(p-amylcinnamoyl)amino-4-chlorobenzoic acid} were less effective than either AACOCF3 or U73122. The phospholipase inhibitors demonstrated selectivity as they did not affect the coronary vasodilator responses to nitroprusside. We obtained additional evidence for the antiphospholipase activity of the inhibitors by demonstrating their capacity to suppress bradykinin-stimulated increases in the release of prostacyclin, measured as 6-keto prostaglandin F1 alpha. The phospholipase inhibitors did not affect cyclooxygenase activity as the ability of arachidonic acid to stimulate prostaglandin formation was unimpaired. These results indicate that the coronary vasodilator action of bradykinin is linked to the activities of both phospholipase C and A2.