Vagal nerve stimulation releases vasoactive intestinal peptide which significantly increases coronary artery blood flow

Objective: To determine the effects of vasoactive intestinal peptide (VIP), released endogenously from cardiac vagal nerves, on coronary artery blood flow (CBF). Methods: We determined the effects of vagal nerve stimulation (VNS) at frequencies of 10, 15, 20, and 30 Hz on left circumflex coronary artery (LCx) blood flow. The increases in CBF during VNS were compared with the increases in CBF produced by exogenous VIP and also nitroglycerin (NTG). In 18 anesthetized open chest mongrel dogs, we blocked the muscarinic and beta-adrenergic receptors with atropine and propranolol. We controlled heart rate and aortic pressure by right atrial pacing and an arterial reservoir. CBF was measured in the LCx with a Doppler flow probe. A 25 gauge catheter was placed in the proximal LCx to inject the MP receptor antagonist [4Cl-D-Phe(6)Leu(17)]VIP, VIP, NTG, or vehicle. CBF, aortic and ventricular pressures, ventricular contractility (+dp/dt(max)) and relaxation (-dp/dt(min)) and the EKG were measured. Results: VNS (0.5 ms, 20 V, 5 min.) at 20 Hz maximally increased CBF by 62+/-14% at 5 min from 71+/-10 to 115+/-19 ml/min (p<0.01). VNS at 10, 15, and 30 Hz increased CBF by 6+/-1%, 24+/-5%, and 24+/-7%, respectively (all p<0.05 vs control). Following 20 Hz VNS, CBF returned toward the baseline over 30 min. Aortic and left ventricular (LV) pressures, LV +dp/dt(max) and LV -dp/dt(min) did not significantly change. After the direct administration of [4Cl-D-Phe(6)Leu(17)]VIP into the LCx, VNS increased CBF by only 10+/-4% (p=NS). Exogenous VIP, in doses of 9.0x10(-11) to 2.1x10(-9) mel, increased CBF by 106+/-17% to 169+/-17% (all p<0.01 vs control). NTG, in doses of 2.2x10(-8) to 1.7x10(-7) mel, increased CBF by 101+/-15% to 169+/-20% (all p<0.01 vs control). These increases in CBF persisted during the 1 to 2 min injection period and returned to the baseline within 5 min. Neither VIP nor NTG significantly changed the heart rate, aortic or LV pressures, LV +dp/dt(max) or LV -dp/dt(min). VNS at 20 Hz, exogenous VIP, 9.0x10(-11) mel, and exogenous NTG, 2.2x10(-8) to 4.4x10(-8) mel, produced equivalent increases in CBF by analysis of variance determination. Conclusion: The present experiments suggest that VNS releases VIP which directly dilates coronary arteries and significantly increases coronary artery blood flow. (C) 1998 Elsevier Science B.V. All rights reserved.