AJP - Gastrointestinal and Liver Physiology, Vol 255, Issue 3 267-G274, Copyright © 1988 by American Physiological Society
Local control of mesenteric blood flow by the renin-angiotensin system
A. Suvannapura and N. R. Levens
Research Department, Ciba-Geigy Corporation, Summit, New Jersey 07901.
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.
