Comparison of inotropic and chronotropic effects of vasoactive intestinal peptide in isolated dog atria
adenylate-cyclase; anesthetized dogs; atrium; autonomic nervous system; cardiac; conscious dogs; contractile force; heart rate; heart rate; isoproterenol; neuropeptide; neuropeptides; Neurosciences & Neurology; parasympathetic; performance; polypeptide; receptor; receptors; Substance P; vip
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 EC(50) 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; Stuesse S L
Journal of the Autonomic Nervous System
1996
1996-12
Journal Article
<a href="http://doi.org/10.1016/s0165-1838(96)00091-4" target="_blank" rel="noreferrer noopener">10.1016/s0165-1838(96)00091-4</a>
Effects of ionic channel antagonists barium, cesium, and UL-FS-49 on vagal slowing of atrial rate in dogs
acetylcholine; atrioventricular nodes; autonomic nervous system; block; cardiac pacemaker; Cardiovascular System & Cardiology; cat; current if; heart rate; ionic currents; pacemaker activity; parasympathetic; Physiology; purkinje-fibers; sinoatrial node cells; sinus node; stimulation; vagus nerves
In response to a brief vagal stimulus, the atrial rate initially slows, then transiently accelerates, and slows a second time. We determined the effects of three antagonists to two ionic channels on this characteristic triphasic pacemaker response. Brief bursts of vagal stimulation were delivered to anesthetized dogs, and atrial cycle lengths were recorded. Either barium, cesium, or UL-FS-49 was administered. Barium, which primarily blocks the acetylcholine-sensitive potassium current (I-K,I-ACh), attenuated the initial vagally induced bradycardia by >50% without affecting the subsequent acceleration or the secondary slowing. Cesium and UL-FS-49 [both of which primarily block the pacemaker current (I-f)] did not affect the initial vagal slowing of atrial rate but abolished the acceleratory portion of the response. The secondary slowing was abolished by cesium but not by UL-FS-49. We conclude that the initial rapid atrial response to acetylcholine is mediated mainly by the I-K,I-ACh, with little contribution from the I-f. The subsequent acceleration is mediated by activation of the I-f.
Wallick D W; Kuguoglu A; Yang T N; Stuesse S L; Levy M N
American Journal of Physiology-Heart and Circulatory Physiology
1997
1997-11
Journal Article
<a href="http://doi.org/10.1152/ajpheart.1997.273.5.h2155" target="_blank" rel="noreferrer noopener">10.1152/ajpheart.1997.273.5.h2155</a>