Effect of vasoactive intestinal peptide on pacemaker location and heart rate in the dog atrium.

Abstract

Vasoactive intestinal polypeptide (VIP) was either injected intravenously (300 pmol.kg-1) or perfused (1 nmol in 1 min) into the sinus node artery (SNA) in anesthetized dogs to study its effect on subsidiary atrial pacemakers. Isochronal maps were obtained from 128 unipolar electrograms recorded on the epicardial surface of both atria in nine animals. When VIP was perfused into the SNA or injected intravenously, heart rate increased by 29 +/- 16% and 12 +/- 12%, and blood pressure decreased by 16 +/- 15 mmHg (1 mmHg = 133.3 Pa) and 24 +/- 18 mmHg, respectively. No significant change in heart rate (3 +/- 6% decrease) accompanied a similar decrease in blood pressure after an intravenous sodium nitroprusside perfusion. The perfusion of VIP into the SNA as well as the intravenous injection of VIP induced a shift of the pacemaker site to the region of Bachmann's bundle in a third of the preparations, while the pacemaker remained in the sinus node area in two thirds. A perfusion of isoproterenol into the SNA produced a similar heart rate increase (32 +/- 14%, NS vs. VIP), and shifted the pacemaker site rostrally within the sinus node in three of five preparations, or to the region of Bachmann's bundle in two of five preparations. The response to VIP in the location of the pacemaker was significantly different from the response to isoproterenol. Repeated perfusions of VIP into the SNA after 10-, 25-, 40-, and 60-min intervals produced 2 +/- 13% (p < 0.005 vs. the effect of first VIP administration), 14 +/- 12% (p < 0.05), 10 +/- 12% (p < 0.05) and 30 +/- 13% (NS) heart rate increases, respectively, thereby demonstrating a tachyphylactic effect. In conclusion, VIP seems to exert its positive chronotropic effect directly (probably via specific VIP receptors), although the phenomenon of tachyphylaxis may suggest an indirect sympathomimetic mechanisms.