EFFECTS OF VASOACTIVE INTESTINAL POLYPEPTIDE ON HEART-RATE IN RELATION TO VAGAL CARDIOACCELERATION IN CONSCIOUS DOGS

Objective: The vagal cardiac accelerator (VCA) system takes part in th e nervous control of the heart rate. In the present study we tried to adduce evidence that vasoactive intestinal polypeptide (VLP) contribut es to vagally induced cardioacceleration. Methods: The effect of VIP o n heart rate and arterial blood pressure was investigated after unmask ing the inherent VCA activity by blocking the sympathetic accelerator and vagal decelerator influences on heart rate in conscious dogs. Resu lts: Following intravenous administration of VIP (10 mu g i.v.) the he art rare increased by 43.6 +/- 6.7 (28.1 +/- 4.7%), from 165.6 +/- 8.5 to 209.1 +/- 7.0 beats/min (P < 0.001) and the mean arterial blood pr essure decreased by 47.5 +/- 3.2 (37.9 +/- 3.0%), from 126.6 +/- 2.6 t o 79.1 +/- 4.9 mmHg CP < 0.001) (n = 11). After VCA activity was refle xly enhanced by alpha(1)-adrenoceptor stimulation with methoxamine, VI P increased heart rate by 36.9 +/- 7.3 (21.5 +/- 4.6%), from 179.8 +/- 5.2 to 216.7 +/- 15.8 beats/min (P < 0.001) and decreased mean arteri al pressure by 79.1 +/- 6.4 (46.7 +/- 3.5%), from 168.2 +/- 4.1 to 89. 1 +/- 5.0 mmHg (P < 0.001). Hence, the VIP-induced tachycardia, expres sed in relative values, shows a significant attenuation after the admi nistration of methoxamine (P < 0.05). The increase in heart rate induc ed by VIP appeared to be inversely related to the prevailing VCA activ ity, both before (r = -0.744, P = 0.009) and after methoxamine (r = -0 .689, P = 0.019). The VIP-induced tachycardia is certainly not reflexl y induced by the fall in arterial pressure, because intracoronary admi nistration of VIP (0.5 mu g i.c.) caused an appreciable increase in th e heart rate by 63.7 +/- 13.0 (46.4 +/- 10.4%), from 143.0 +/- 8.1 to 208.7 +/- 12.0 beats/min (P < 0.005), whereas the mean arterial pressu re only slightly changed (-7.7 +/- 2.0 mmHg) (P < 0.05) (n = 6). In ad dition, VIP (10 mu g i.v.) also caused a tachycardia in vagotomized do gs with blocked P adrenergic and muscarinic receptors. The administrat ion of the VIP antagonists [D-p-Cl-Phe(6),Leu(17)]-VIP (50-150 mu g i. c.) and [Lys(1),Pro(2,5),Leu(17)]-VTP (20 mu g i.c.) did not result in alterations in VCA activity nor did the VIP antagonists block the VCA reflex response to a rise in arterial pressure. However, none of the VIP antagonists reduced the VIP-induced tachycardia either. Conclusion : Vasoactive intestinal polypeptide is likely to play a part in the va gal cardiac accelerator system. However, conclusive evidence for its r ole as the terminal transmitter in the VCA pathway will have to wait f or the availability of a specific cardiac VIP receptor antagonist.