Age-dependent alterations in the efficacy of phenylephrine-induced contractions in vascular smooth muscle isolated from the corpus cavernosum of impotent men

Abstract

Steady-state contractile responses elicited by phenylephrine activation of the α1-adrenergic receptor subtype were studied in vascular smooth muscle strips isolated from the corpus cavernosum of impotent men. The dissociation constant of phenylephrine was determined by the method of partial irreversible receptor inactivation over a wide range of α1-adrenergic receptor alkylation levels. Statistical analysis of mean population values revealed a significantly greater mean efficacy for phenylephrine-induced contractions in older patients (60–73 years old) than in younger patients (40–59 years old), in the absence of similar alterations in the mean phenylephrine dissociation constant (affinity). In addition, there was no significant effect of the diabetic state on the mean phenylephrine affinity or efficacy estimates. However, despite the absence of age-or pathology-dependent variations in agonist affinity, as assessed by group mean calculations, a detailed examination of all isolated tissues on an individual basis revealed that the phenylephrine affinity estimates varied over a range of almost two orders of magnitude. Furthermore, a linear regression analysis revealed a highly significant positive correlation between agonist affinity and the location of the phenylephrine concentration–response curve, which was characterized by a slope significantly less than unity. In conclusion, an increased efficacy of phenylephrine-induced contractions in vitro is consistent with the hypothesis that augmented corporal vascular smooth muscle contractility in vivo may contribute to the pathophysiology of impotence in older patients.Key words: phenylephrine, α1-adrenergic receptor, human vascular smooth muscle, efficacy, impotence, corpus cavernosum.