Deaminovasopressin has direct and modulatory effects on ventricular automaticity in the rat heart.

OBJECTIVE: Some neuropeptides have direct cardiac effects and also modulate the cardiac effects of catecholamines. Vasopressin is an abundantly available neuropeptide having well known interactions with catecholamines in vascular smooth muscle. The aim of this study was to determine the direct and modulatory effects of vasopressin on ventricular automaticity. METHODS: The cardiac effects of deaminovasopressin (dAVP), a long acting synthetic analogue of vasopressin, were tested on basal and alpha 1 agonist induced changes in automaticity in isolated ventricular septal preparations from adult and neonatal rats after chronic exposure (10 micrograms.kg-1 x d-1 subcutaneously for 10 d) and acute exposure (in vitro bath superfusion with 10(-8) M dAVP for 1 h). RESULTS: Chronic exposure to dAVP decreased basal ventricular automaticity in the adult and in 10-11 d old rats. Although alpha 1 agonists tended to decrease automaticity in adult rat heart, prior chronic dAVP exposure altered the chronotropic response to alpha 1 agonist so that only an increase in automaticity was observed. A similar result was seen in adult ventricular septal preparations upon acute superfusion with dAVP. Acute dAVP exposure reduced basal ventricular automaticity, and modified the alpha 1 adrenergic chronotropic response, such that only an increase in automaticity occurred. Acute dAVP exposure in adult ventricular septal preparations did not significantly change total alpha 1 adrenergic receptor density or antagonist affinity, alpha 1 adrenergic receptor subtype expression, or the amount of pertussis toxin sensitive G protein measured in an ADP ribosylation assay. CONCLUSION: dAVP not only exerted direct effects of chronotropy, but also influenced the expression of alpha 1 adrenergic chronotropic responsiveness. If vasopressin has a similar action, this may have important implications in instances where levels of this peptide are raised. For example, surgical stress and cardiopulmonary 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 settings.