Facilitation of noradrenergic transmission by angiotensin in hypertensive rats.
We examined the angiotensin-induced potentiation of noradrenergic transmission in the isolated mesenteric arteries of one-kidney, one clip (1K1C) hypertensive rats. The angiotensin converting enzyme activity measured in plasma did not change during the development of hypertension, whereas the activity measured in the aortic tissue was significantly augmented 28 days after the renal artery was clipped. Although the pressor responses to nerve stimulation were basically unaltered, a significant increase in the sensitivity to norepinephrine developed during hypertension. The 1K1C preparations presented an increased sensitivity to the facilitatory effect of angiotensin II on the response to periarterial nerve stimulation. The facilitatory effect of angiotensin II on both nerve stimulation and exogenous norepinephrine was blocked by saralasin. Angiotensin I induced similar facilitatory action on noradrenergic transmission that was inhibited by saralasin. When a high concentration of angiotensin I was used, the facilitatory effect was significantly higher in mesenteric arteries from 1K1C rats than in controls. Captopril reduced the facilitatory effect of angiotensin I in 1K1C preparations, whereas the responses of the normotensive control rats were unaffected by captopril. These findings are consistent with angiotensin I acting directly on angiotensin II receptors or with angiotensin I being converted to angiotensin II by an alternative pathway not involving angiotensin converting enzyme.
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Department of Pharmacology, School of Medicine, University of São Paulo, Ribeirão Prêto, Brazil.
Salgado
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D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000201:enzymology; D001794:Blood Pressure / Q000502:physiology; D002216:Captopril / Q000494:pharmacology; D004357:Drug Synergism; D006978:Hypertension, Renovascular / Q000503:physiopathology*; D008297:Male; D009638:Norepinephrine / Q000502:physiology*; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D012504:Saralasin / Q000494:pharmacology; D013566:Sympathomimetics / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects
D013566:Sympathomimetics; D000804:Angiotensin II; D002216:Captopril; D007703:Peptidyl-Dipeptidase A; D012504:Saralasin; D009638:Norepinephrine