Angiotensin II potentiates vasodilation of rat aorta by cAMP elevating agonists

We previously observed an effect of the Ca++-mobilizing peptide, angiotensin II (ANG II), to potentiate agonist-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) formation in rat cultured aortic smooth muscle cells. Consequently, it was postulated that the relaxant effects of dilator agents that act through cAMP formation would be enhanced in the presence of ANG II. To test this idea, we examined the influence of ANG II on agonist-induced relaxation of rat isolated aortic rings. Angiotensin II (0.1 microM) evoked a transient increase in the tone of KCI (30 mM)-precontracted aortae that returned to the original level of induced tension after about 20 min. Subsequent application of isoproterenol caused a concentration-dependent relaxation that was significantly greater in preparations pretreated with ANG II than in time-matched controls. Similarly, isoproterenol-induced relaxations of aortae precontracted with either phenylephrine (1 microM) or endothelin 1 (3 nM) were also augmented after ANG II treatment. The principal action of ANG II was to enhance the maximal relaxation evoked by isoproterenol without affecting the EC50 value, irrespective of the contractile agent used. This potentiating effect of ANG II was not specific for beta adrenoceptor-mediated relaxation because the relaxant response to iloprost, a prostaglandin I2 analog, was also increased after ANG II treatment. The effect of ANG II to enhance isoproterenol-induced relaxation was maintained in endothelium-denuded preparations. However, ANG II did not enhance the relaxation of vessels evoked through either the direct elevation of cAMP levels by dibutyryl cAMP or the stimulation of cyclic 3',5'-guanosine monophosphate formation by sodium nitroprusside. The data indicate that exposure of rat aortae to the constrictor peptide ANG II enhances the vasodilation of these blood vessels by agonists that stimulate cAMP formation. Such cross-talk between constrictor and dilator pathways could represent an important mechanism in the modulation of vascular tone.