Hemodynamic effects of angiotensin II and the influence of angiotensin receptor antagonists in pithed XXXX .

@entity1169 @entity101 @entity73191 @entity95 @entity9886 @entity45929 @entity73192 @entity1063
We investigated the cardiovascular effects of angiotensin II (AII) and the influences of four angiotensin receptor antagonists: @entity9886 , @entity45929 , @entity73191 , and @entity73192 in the pithed @entity95 preparation. AII (0.03-10 nmol/kg) elicited a dose-dependent increase in blood pressure (BP), left ventricular pressure (LVP), LV end-diastolic pressure (LVEDP), dP/dtmax, and heart rate (HR). The maximal @entity101 effect of AII is comparable to that of @entity1063 (NE), but its effects on LVEDP and HR are weaker than those of NE. On a molar base, AII is approximately 27 times more potent than NE. @entity1169 (0.5 mg/kg i.v.) did not significantly influence the AII-induced increase in diastolic BP (DBP) and LVEDP, but it abolished AII-induced positive chronotropic effects over the entire dose range of angiotensin AII studied. @entity9886 , but not @entity45929 , shifted the dose-response curves for AII to the right in a parallel manner. @entity73191 and @entity73192 also caused rightward shifts of the AII dose-response curve. These experiments indicate that in @entity1169 -treated pithed @entity95 AII causes vasoconstrictor effects in both resistance vessels and in the venous system, which are both mediated by AT1- but not by AT2-receptors. The AII-induced positive chronotropic effect is an indirect action mediated by the stimulation of postsynaptic beta 1-adrenoceptors. @entity73191 and @entity73192 , two new nonpeptide angiotensin receptor blockers that have affinity for both AT1- and AT2-receptors are also potent antagonists of the cardiovascular effects of AII in pithed @entity95 .
