Local control of mesenteric blood flow by the renin-angiotensin system.
The purpose of this study is to determine whether locally acting angiotensin II (ANG II) plays a direct role in the control of mesenteric blood flow after volume depletion in the anesthetized dog. Infusion of the ANG II receptor antagonist saralasin into the mesenteric artery at doses between 0.05 and 0.1 microgram.kg-1.min-1 attenuated the reduction in renal blood flow produced by intrarenal injection of ANG II. In contrast, infusion of saralasin at 0.01 microgram.kg-1.min-1 did not affect the change in renal blood flow produced by ANG II, indicating that at this dosage the antagonist did not leave the mesenteric circulation in pharmacologically significant quantities. ANG II produced a dose-dependent decrease in splanchnic blood flow when injected into the mesenteric artery. Simultaneous infusion of 0.01 microgram.kg-1.min-1 saralasin into the mesenteric artery blocked the action of up to 1 ng ANG II by 80%. Infusion of saralasin at 0.01 microgram.kg-1.min-1 into the mesenteric artery of hemorrhaged animals increased mesenteric blood flow without significantly affecting renal blood flow, blood pressure, or plasma renin activity. These data demonstrate that saralasin can be localized to the mesenteric circulation at a dose capable of inhibiting angiotensin action and that endogenous ANG II plays a direct, physiologically important local role in controlling splanchnic resistance after volume depletion.
Suvannapura
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A
Research Department, Ciba-Geigy Corporation, Summit, New Jersey 07901.
Levens
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NR
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006470:Hemorrhage / Q000503:physiopathology; D008297:Male; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects; D012084:Renin-Angiotensin System; D012504:Saralasin / Q000494:pharmacology; D013152:Splanchnic Circulation / Q000187:drug effects
D000804:Angiotensin II; D012504:Saralasin