KINETIC CHARACTERISTICS OF ALPHA-1-ADRENERGIC CONTRACTIONS IN HUMAN CORPUS CAVERNOSUM SMOOTH-MUSCLE

Kinetic studies were conducted on the contractile response elicited by phenylephrine (PE) activation of the alpha(1)-adrenergic receptor subtype in vascular smooth muscle isolated from the corpus cavernosum of impotent men. PE-induced contractions were separated into distinct phasic and tonic components, and the tonic portion was analyzed using a first-order rate equation to determine the maximal rate constant for onset of contraction (k(obs max)) and the maximum amplitude of the steady-state contractile response (R(eq max)). The k(obs max)) value in tissues from insulin-dependent diabetic patients was significantly greater than that in tissues from either noninsulin-dependent diabetics or nondiabetics. Additionally, the mean k(obs max) value in older patients (60-70 yr) was significantly greater than the mean k(obs max) value in younger patients (32-59 yr). Significant diabetes-related, but not age-related, alterations were also found in R(eq max). The observed changes in contractility resulted in dramatic age- and pathology-dependent alterations in the initial rate and/or magnitude of PE-induced response generation. These kinetic studies extend our previous observations at steady state and provide further evidence for heightened corporal tissue tone in the etiology of erectile dysfunction.