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

• Published in: Cardiovascular research 1993-09, Vol.27 (9), p.1624-1628
• Main Authors: Sun, Lena S, Sawyer, Wilbur H, Steinberg, Susan F, Rosen, Michael R
• Format: Article
• Language: English
• Subjects: Animals; arrhythmias; Biological and medical sciences; Culture Techniques; Deamino Arginine Vasopressin - pharmacology; deaminovasopressin; Fundamental and applied biological sciences. Psychology; Heart; Heart Rate - drug effects; Heart Ventricles - drug effects; Phenylephrine - pharmacology; Rats; Rats, Wistar; Receptors, Adrenergic, alpha - drug effects; ventricular automaticity; Vertebrates: cardiovascular system; α adrenergic receptors
• ISSN: 0008-6363; 1755-3245
• DOI: 10.1093/cvr/27.9.1624

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 α1 agonist induced changes in automaticity in isolated ventricular septal preparations from adult and neonatal rats after chronic exposure (10 μg·kg−1·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 α1 agonists tended to decrease automaticity in adult rat heart, prior chronic dAVP exposure altered the chronotropic response to α1 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 α1 adrenergic chronotropic response, such that only an increase in automaticity occurred. Acute dAVP exposure in adult ventricular septal preparations did not significantly change total α1 adrenergic receptor density or antagonist affinity, α1 adrenergic receptor subtype expression, or the amount of pertussis toxin sensitive G protein measured in an ADP ribosylation assay. Conclusions: dAVP not only exerted direct effects of chronotropy, but also influenced the expression of α1 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. Cardiovascular Research 1993; 27:1624-1628