Potentiation of cyclic AMP-mediated vasorelaxation by phenylephrine in pulmonary arteries of the rat

1 alpha(1)-adrenoceptor agonists may potentiate relaxation to beta-adrenoce ptor agonists, although the mechanisms are unclear. We compared relaxations induced by beta-adrenoceptor agonists and cyclic AMP-dependent vasodilator s in rat pulmonary arteries constricted with prostaglandin F-2 alpha (PGF(2 alpha)) or the alpha(1)-adrenoceptor agonist phenylephrine (PE). In additi on, we examined whether differences were related to cyclic AMP- or nitric o xide (NO) and cyclic GMP-dependent pathways. 2 Isoprenaline-induced relaxation was substantially potentiated in arteries constricted with PE compared with PGF(2 alpha). Methoxamine was similar to PE, whereas there was no difference between PGF(2 alpha) and 30 mM KCl. Th e potentiation was primarily due to a marked increase in the NO-independent component of relaxation, from 9.1+/-1.7% for PGF(2 alpha) to 55.1+/-4.4% f or PE. NO-dependent relaxation was also enhanced, but to a lesser extent (s imilar to 50%). Relaxation to salbutamol was almost entirely NO-dependent i n both groups, and was potentiated similar to 50% by PE. 3 Relaxation to forskolin (activator of adenylate cyclase) was also enhance d in PE constricted arteries. Part of this relaxation was NO-dependent, but the major effect of PE was to increase the NO-independent component. Propr anolol diminished but did not abolish the potentiation. There was no differ ence in response to CPT cyclic AMP (membrane permeant analogue) between PE and PGF(2 alpha), suggesting that mechanisms distal to the production of cy clic AMP were unchanged. 4 Relaxation to sodium nitroprusside (SNP) was the same for PE and PGF(2 al pha), although relaxation to acetylcholine (ACh) was slightly depressed. Th is implies that potentiation by PE does not involve the cyclic GMP pathway directly. 5 Mesenteric arteries constricted with PE did not show potentiation of isop renaline-induced relaxation compared to those constricted with PGF(2 alpha) , suggesting that this effect may be specific to the pulmonary circulation. 6 These results clearly show that PE potentiates both the NO-independent an d -dependent components of cyclic AMP-mediated relaxation in pulmonary arte ries of the rat, although the effect on the former is more profound. We sug gest that potentiation of both components is largely due to direct activati on of adenylate cyclase via alpha(1)-adrenoceptors, within the smooth muscl e and endothelial cells respectively.