DUAL-ACTION OF ANGIOTENSIN-II ON CORONARY RESISTANCE IN THE ISOLATED-PERFUSED RABBIT HEART

Citation
I. Porsti et al., DUAL-ACTION OF ANGIOTENSIN-II ON CORONARY RESISTANCE IN THE ISOLATED-PERFUSED RABBIT HEART, Naunyn-Schmiedeberg's archives of pharmacology, 348(6), 1993, pp. 650-658
Citations number
40
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Pharmacy
ISSN journal
0028-1298
Volume
348
Issue
6
Year of publication
1993
Pages
650 - 658
Database
ISI
SICI code
0028-1298(1993)348:6<650:DOAOCR>2.0.ZU;2-V
Abstract
We studied the functional role of angiotensin II (AII) receptor subtyp es and vasodilatory endothelial autacoid release in response to AII in isolated perfused rabbit hearts. AII infusion induced biphasic change s in coronary perfusion pressure (CPP): an initial increase was follow ed by a decrease until a plateau was reached. At higher concentrations of AII (greater-than-or-equal-to 10 nmol/1) this plateau phase was lo wer than the initial CPP level. AII infusion elicited inverse changes in peak left ventricular pressure (LVP): coronary constriction was ass ociated with a transient decline, and during the plateau phase LVP was clearly increased. AII also moderately augmented prostacyclin (PGI2) release from the coronary vascular bed. The AII-induced changes in CPP , LVP, and PGI2 release were effectively inhibited by the AT1 receptor subtype antagonist ICI D8731 (30 nmol/1), but not by the AT2 receptor antagonist CGP 42112 (30 nmol/1). The adenosine A1 receptor antagonis t 8-phenyltheophylline (0.1 mumol/l) attenuated the decline in CPP fol lowing the constriction phase without affecting the changes in LVP dur ing AII infusion. The cyclooxygenase inhibitor diclofenac (I mmol/1) h ad no effect on the AII-induced changes in CPP, whereas the nitric oxi de-synthase inhibitor N(G)-nitro-L-arginine (30 mumol/1) markedly pote ntiated the vasoconstriction but was without effect on the plateau pha se of the response. In contrast to AII, the thromboxane analogue U4661 9 elicited sustained increases in CPP which were associated with sligh t decreases in LVP. In conclusion, AII induced a biphasic pressor resp onse in the rabbit coronary vascular bed consisting of a transient vas oconstriction followed by a dilatation especially at higher concentrat ions of AII, an effect which was independent of the endothelial autaco ids nitric oxide and PGI2. The AII-induced dilatation probably reflect ed rapid desensitization of the coronary arterial smooth muscle to the constrictor effect, and the concomitant accumulation of vasodilatory metabolites such as adenosine, generated during the positive inotropic action of AII. All the effects of AII in the rabbit heart appeared to be mediated via the AT, receptor subtype localized on coronary endoth elial and smooth muscle cells, as well as on cardiomyocytes.