Comparison of inotropic and chronotropic effects of vasoactive intestinal peptide in isolated dog atria.
The positive chronotropic and inotropic effects of vasoactive intestinal peptide, VIP, were studied in an isolated canine right atrial preparation. Atria were removed, maintained in a bath, and perfused with Tyrode's solution. Contractile force and atrial depolarization were measured. VIP (18.8-600 pmol) was injected into a cannulated sinoatrial nodal artery and dose response curves were obtained. The mean EC50 was similar for the inotropic and the chronotropic responses (136 and 144 pmol, respectively). Time courses of the onset and of recovery from the responses were measured. Times for onset of VIP effects were similar but, once the effect was initiated, rate of development of the response and recovery time from the responses were dose dependent. The increases in atrial rate lasted two to four times longer than did the increases in contractile force. Recovery from the chronotropic and inotropic responses to VIP differ, suggesting that the intracellular responses are coupled differently to the receptors. The responses to VIP were compared to those of 100 pmol isoproterenol, another positive chronotropic and inotropic agent. Isoproterenol was a slightly more potent chronotropic and inotropic agent than VIP. Desensitization of the responses was determined. Repeated exposures to VIP decreased the chronotropic response but not the inotropic response to VIP. There was no significant decrease in responsiveness to isoproterenol.
Wallick
D W
DW
Division of Investigative Medicine, Mt. Sinai Medical Center, Cleveland, OH 44106, USA.
Stuesse
S L
SL
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D013997:Time Factors; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D000318:Adrenergic beta-Agonists; D002316:Cardiotonic Agents; D014660:Vasoactive Intestinal Peptide; D007545:Isoproterenol