Obligatory role for endogenous endothelin in mediating the hypertrophic effects of phenylephrine and angiotensin II in neonatal rat ventricular myocytes: evidence for two distinct mechanisms for endothelin regulation

Various Gq protein-coupled receptor agonists such as the 1 adrenoceptor agonist phenylephrine, angiotensin II, and endothe-lin-1 are potent hypertrophic factors. There is evidence of potential cross talk between these agents, particularly in terms of endothe-lin-1 as playing a central role in mediating the actions of other hypertrophic factors. Using cultured rat neonatal ventricular myo-cytes, we assessed the potential cross talk between these factors and sought to examine the potential underlying mechanisms. Twenty-four-hour exposure to either agent produced significant hypertrophy as determined by cell size and molecular markers. Although the hypertrophic effects of phenylephrine and angioten-sin II were expectedly prevented by 1 and AT1 receptor antago-nists, respectively, these effects were also blocked by the ETA receptor antagonist BQ123 [cyclo(D-Asp-Pro-D-Val-Leu-D-Trp)