AUGMENTATION IN THE KINETIC CHARACTERISTICS OF PHENYLEPHRINE-INDUCED AND 5-HYDROXYTRYPTAMINE-INDUCED CONTRACTIONS IN THE ISOLATED RAT AORTA FOLLOWING 8 WEEKS OF STZ-DIABETES

Kinetic studies were conducted on the contractile response elicited by phenylephrine (PE) and 5-hydroxytryptamine (5-HT) activation of the alpha(1)-adrenergic- and 5-HT2 receptor subtypes, respectively, in aortic rings isolated from streptozotocin (STZ)-diabetic and age-matched control rats. The maximal PE- and 5-HT-induced contractile responses were separated into distinct phasic and tonic components, and the tonic portion of the response was assessed by evaluation of the calculated maximal rate constant for onset of contraction (k(obsmax); min(-1)). Statistical analysis revealed that the mean k(obsmax) values for PE alone (10 mu M), 5-HT alone (10 mu M) and mixtures of PE and 5-HT (10 mu M each) were significantly greater in diabetic animals than in age-matched control animals. These increases in k(obsmax) resulted in significant diabetes-related increases in the rate and relative magnitude of response generation during the initial minutes of contraction. Such observations emphasize the importance of kinetic studies, and given the central role played by the aorta in cardiovascular homeostasis, suggest that altered aortic contractility may play a role in some aspects of diabetic vascular disease. Moreover, if these kinetic alterations reflect a more generalized feature of diabetic vasculature (e.g., resistance vessels), then it is conceivable that such changes may further exacerbate diabetic vasculopathy.