Abstract
[1-Sarcosine, 8-isoleueine]angiotensin II, a competitive antagonist of angiotensin II in vitro, was evaluated in dogs to determine whether it would block the pressor response to exogenous angiotensin II and abolish the hypertension resulting from endogenously produced angiotensin II generated after renal artery constriction. The antagonistic effects of this analog against the cardiovascular effects of angiotensin II mediated by the central and peripheral sympathetic nervous systems were also investigated. [Sar1, Ile8]angiotensin II (0.2 µg/kg/min) significantly reduced the pressor response to exogenous angiotensin II, but did not alter the response to i.v. norepinephrine. It also completely antagonized the hypertensive response after acute reduction of renal blood flow in dogs. In the perfused hind paw, in which sympathetically mediated vasoconstrictor responses to tyramine and sympathetic nerve stimulation were enhanced by angiotensin II, [Sar1, Ile8]angiotensin II significantly decreased these potentiated responses. The cardiovascular response to infusion of angiotensin II into the vertebral artery was abolished by vertebral artery infusion of [Sar1, Ile8]angiotensin II. These results are consistent with previous studies with this analog which suggested that [Sar1, Ile8]angiotensin II is a specific antagonist of the direct vascular actions of angiotensin II as well as of those effects of angiotensin II which are mediated by the central and peripheral nervous systems.
Footnotes
- Received August 7, 1972.
- Accepted December 5, 1972.
- © 1973 by The Williams & Wilkins Company
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