EFFECT OF VASOACTIVE-INTESTINAL-PEPTIDE ON PACEMAKER LOCATION AND HEART-RATE IN THE DOG ATRIUM

Vasoactive intestinal polypeptide (VIP) was either injected intravenou sly (300 pmol kg(-1)) or perfused (1 nmol in 1 min) into the sinus nod e artery (SNA) in anesthetized dogs to study its effect on subsidiary atrial pacemakers. Isochronal maps were obtained from 128 unipolar ele ctrograms recorded on the epicardial surface of both atria in nine ani mals. When VIP was perfused into the SNA or injected intravenously, he art rate increased by 29 +/- 16% and 12 +/- 12%, and blood pressure de creased by 16 +/- 15 mmHg (1 mmHg = 133.3 Pa) and 24 +/- 18 mmHg, resp ectively. No significant change in heart rate (3 +/- 6% decrease) acco mpanied a similar decrease in blood pressure after an intravenous sodi um nitroprusside perfusion. The perfusion of VIP into the SNA as well as the intravenous injection of VIP induced a shift of the pacemaker s ite 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 rost rally within the sinus node in three of five preparations, or to the r egion of Bachmann's bundle in two of five preparations. The response t o VIP in the location of the pacemaker was significantly different fro m the response to isoproterenol. Repeated perfusions of VIP into the S NA 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, resp ectively, thereby demonstrating a tachyphylactic effect. In conclusion , VIP seems to exert its positive chronotropic effect directly (probab ly via specific VIP receptors), although the phenomenon of tachyphylax is may suggest an indirect sympathomimetic mechanism.