Independent roles of prostaglandins and the renin-angiotensin system in abnormal vascular reactivity in Bartter's syndrome.
To clarify the independent roles of prostaglandins and the renin-angiotensin system in the pressor resistance to angiotensin II in Bartter's syndrome, the pressor responsiveness to exogenous angiotensin II was investigated in three patients with the syndrome during the administration of indomethacin synthesis, and captopril is an angiotensin-converting enzyme inhibitor. All the patients showed high plasma renin activity, increased urinary excretion of prostaglandin E, and pressor resistance of angiotensin II. An analogue of angiotensin II that had weak agonistic properties induced a marked fall in blood pressure. Pretreatment with indomethacin (150 mg/day) decreased baseline plasma renin activity and reversed the hypotensive effect of the analogue of angiotensin II. Apparently, our data support the concept that pressor resistance ultimately results from the increase in the concentration of endogenous angiotensin II. However, the augmentation of indomethacin was significantly (p less than 0.01) greater in magnitude than the response obtained with captopril, although the concentration of plasma angiotensin II prior to each infusion of angiotensin II was the same. This observation could be explained by the finding that indomethacin suppressed both systems, but captopril inhibited only the renin-angiotensin system. Evidence presented herein suggests that the abnormalities in the vascular reactivity to angiotensin II may result from, not only the decreased number of receptor sites as a results of the increased concentration of endogenous angiotensin II, but also from the alteration of the end-organ sensitivity to angiotensin II via overproduction of prostaglandins.
D000328:Adult; D001477:Bartter Syndrome / Q000503:physiopathology*; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology; D015232:Dinoprostone; D005260:Female; D006801:Humans; D006929:Hyperaldosteronism / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D011458:Prostaglandins E / Q000037:antagonists & inhibitors / Q000097:blood*; D012084:Renin-Angiotensin System / Q000187:drug effects*
D011458:Prostaglandins E; D002216:Captopril; D015232:Dinoprostone; D007213:Indomethacin