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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Acetylcholine, Animals, Cyclooxygenase Inhibitors, Dose-Response Relationship, Drug, Endothelin Receptor Antagonists, Endothelium, Vascular, Enzyme Inhibitors, Hypertension, In Vitro Techniques, Indomethacin, Male, Mesenteric Arteries, Muscle Contraction, NG-Nitroarginine Methyl Ester, Phenylephrine, Phenylpropionates, Pyrimidines, Rats, Rats, Inbred SHR, Rats, Inbred WKY, Receptor, Endothelin A, Regional Blood Flow, Stress, Mechanical, Vasoconstrictor Agents, Vasodilation.
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Does chronic blockade of endothelin ETA receptors improve flow dependent dilation in resistance arteries of hypertensive rats? Context: Flow (shear stress)-induced dilation (FD) is attenuated in hypertension. Flow triggers the release by endothelial cells of dilators, such as NO or cyclo-oxygenase (COX) derivatives and constrictor factors such as endothelin-1 (ET-1) which might be involved in several cardiovascular diseases. We hypothesized that ET-1 might play a functional role in FD and participate in the endothelial dysfunction in hypertension. We investigated the effect of chronic treatment with the ETA receptor blocker LU135252 (50 mg/kg/day) for 2 weeks on the dilator response to flow in normotensive (Wistar-Kyoto; WKY) or hypertensive (SHR, n = 7 or 8 per group) rats. Systolic arterial pressure was not significantly affected by chronic ETA receptor blockade in both strains. In mesenteric resistance arteries (diameter: approximately 100 microns), isolated in vitro, FD was lower and myogenic tone higher in SHR than in WKY rats. Chronic ETA receptor blockade increased FD by 73% (7.5 +/- 1.5 to 13.0 +/- 2.7 microns dilation with a flow-rate of 150 microliters/min) in SHR (no effect in WKY). The participation of NO to FD was increased in SHR and the participation of dilator COX product(s) (blocked by indomethacin 10 mumol/l) to FD was significantly increased in SHR and in WKY. In control rats FD was improved by acute ETA receptor blockade in WKY rats (18.5 +/- 2.0 to 23.2 +/- 1.8 microns dilation to flow-rate of 150 microliters/min) and significantly more in SHR (6.0 +/- 1.8 to 15.1 +/- 1.6 microns). Acetylcholine-induced dilation was also improved by chronic ETA receptor blockade (no effect of an acute blockade). Myogenic and phenylephrine-induced tone were not affected by chronic or acute ETA receptor blockade. The improvement of endothelium-dependent dilation was not related to a change in blood pressure.
assistant
Chronic ETA receptor blockade increased flow-induced dilation in SHR possibly by suppressing flow-induced ETA stimulation and by improving the release of dilator products by the endothelium. Final Decision: yes