DEAMINOVASOPRESSIN HAS DIRECT AND MODULATORY EFFECTS ON VENTRICULAR AUTOMATICITY IN THE RAT-HEART

Objective: Some neuropeptides have direct cardiac effects and also mod ulate the cardiac effects of catecholamines. Vasopressin is an abundan tly available neuropeptide having well known interactions with catecho lamines in vascular smooth muscle. The aim of this study was to determ ine the direct and modulatory effects of vasopressin on ventricular au tomaticity. Methods: The cardiac effects of deaminovasopressin (dAVP), a long acting synthetic analogue of vasopressin, were tested on basal and alpha1 agonist induced changes in automaticity in isolated ventri cular septal preparations from adult and neonatal rats after chronic e xposure (10 mug.kg-1.d-1 subcutaneously for 10 d) and acute exposure ( in vitro bath superfusion with 10(-8) M dAVP for 1 h). Results: Chroni c exposure to dAVP decreased basal ventricular automaticity in the adu lt and in 10-11 d old rats. Although ot, agonists tended to decrease a utomaticity in adult rat heart, prior chronic dAVP exposure altered th e chronotropic response to alpha1 agonist so that only an increase in automaticity was observed. A similar result was seen in adult ventricu lar septal preparations upon acute superfusion with dAVP. Acute dAVP e xposure reduced basal ventricular automaticity, and modified the alpha 1 adrenergic chronotropic response, such that only an increase in auto maticity occurred. Acute dAVP exposure in adult ventricular septal pre parations did not significantly change total alpha1 adrenergic recepto r density or antagonist affinity, alpha1 adrenergic receptor subtype e xpression, or the amount of pertussis toxin sensitive G protein measur ed in an ADP ribosylation assay. Conclusions: dAVP not only exerted di rect effects of chronotropy, but also influenced the expression of alp ha1 adrenergic chronotropic responsiveness. If vasopressin has a simil ar action, this may have important implications in instances where lev els of this peptide are raised. For example, surgical stress and cardi opulmonary bypass are clinical situations associated with increases in both vasopressin and catecholamine levels. An interaction between the two may contribute to the development of tachyarrhythmias in these se ttings.