THE EFFECTS OF SAR¹ALA⁸‐ANGIOTENSIN II IN VASOPRESSIN‐TREATED DEHYDRATED SHEEP

Abstract

SUMMARYMildly dehydrated conscious Merino ewes were infused with vasopressin (AVP) at 5 mu. min-' alone and simultaneously with the angiotensin II receptor blocker sarlala8-angiotensin II (saralasin) at 15 ug . min-m. AVP was slightly pressor and produced an increase in the calculated total peripheral resistance, and an increase in glomerular filtration rate, urine flow and electrolyte excretion, without a change in total renal plasma flow. These results indicate renal efferent arteriolar vasoconstriction as well as other non-renal vasoconstriction. Saralasin infusion checked the rise in total peripheral resistance (which continued to increase after saralasin withdrawal), but caused a marked increase in renal vascular resistance resulting in a decrease in renal plasma flow and to a lesser extent in glomerular filtration rate. These results suggest that saralasin was acting as an angiotensin II agonist in the kidney, but as an antagonist elsewhere. Deductions from previous experiments in the literature of the renal function of angiotensin II, based on its supposed inhibition by saralasin, may not be justified.

Converting‐enzyme Inhibition and 1‐sarcosine‐8‐isoleucine‐angiotensin Ii: Effects on Renal Function in the Dehydrated Sheep

“…The results of these experiments and others, in which the interaction of All and AVP was examined (Kelly, Wholohan & Yesberg, 1983), did not provide conclusive evidence for this role ofAll in dehydrated sheep. This was due at least partly to the fact that saralasin exhibited a selective agonist effect in the kidney, though antagonist elsewhere.…”

“…fell only slightly compared with the significant fall in G.F.R., it is likely that there was not only vasoconstriction (A ll agonist) at the afferent arteriole but also vasodilatation (A ll antagonist) at the efferent arteriole. A selective A II antagonist effect at the efferent arteriole was also postulated to explain the effects of saralasin in dehydrated sheep (Yesberg et al 1982), although in sheep simultaneously infused with AVP, only the All-agonist effect was observed (Kelly et al 1983). This latter observation could have been due to the post-glomerular vasoconstrictor effect of AVP in dehydrated sheep previously described (Yesberg et al 1979).…”

“…The contribution ofendogenous A II to low urine volumes of deydrated sheep was studied by blocking the AII receptor with an analogue, 1-sarcosine-8-alanine-AII (saralasin) (Yesberg, Henderson, Wilson, Law & Cross, 1982). The results of these experiments and others, in which the interaction of All and AVP was examined (Kelly, Wholohan & Yesberg, 1983), did not provide conclusive evidence for this role ofAll in dehydrated sheep. This was due at least partly to the fact that saralasin exhibited a selective agonist effect in the kidney, though antagonist elsewhere.…”