| Abstract
| - Objective:. To determine the effects of vasoactive intestinal peptide, released from the right and left vagal nerves, on ventricular contraction, relaxation, and heart rate. Methods: The muscarinic and β-adrenergic receptors were blocked with atropine and propranolol, and afterload was controlled in 48 anesthetized, open-chest mongrel dogs. Experiments were performed in the absence (Series 1, 10 dogs) and in the presence (Series 2, 22 dogs) of a controlled heart rate and prior to and after the administration of a sensitive and selective vasoactive intestinal peptide antagonist (Series 3, 16 dogs). Results: Right ventricular contraction (+dp/dtmax), relaxation (−dp/dtmin) and heart rate increased significantly during 20 Hz vagal nerve stimulation for 5 min. Vagal nerve stimulation in Series 1 increased right ventricular +dp/dtmax by 28% from a control value of 480 ± 11 (P< 0.001) and right ventricular −dp/dtmin by 23% from a control value of 341 ± 11 (P< 0.002). Left ventricular +dp/dtmax and −dp/dtmin increased slightly but not significantly. Vagal nerve stimulation also increased the heart rate by 29% from a control value of 149 ± 2 (P< 0.001). During controlled heart rate in Series 2, vagal nerve stimulation at 20 Hz consistently increased right ventricular +dp/dtmax and −dp/dtmin comparable to Series 1 experiments but did not increase left ventricular +dp/dtmax or −dp/dtmin. Injection of the vasoactive intestinal peptide antagonist [4C1-D-Phe6,Leu17]VIP into the right coronary artery of 16 dogs in Series 3 did not affect right ventricular +dp/dtmax, −dp/dtmin, or heart rate. However, this antagonist substantially decreased the vagal-induced increases in right ventricular +dp/dtmax, −dp/dtmin, and heart rate by 85, 63, and 71% (P< 0.005), respectively. Conclusion: The present experiments suggest that vagal nerve stimulation releases vasoactive intestinal peptide (VIP) or a ‘VIP-like substance’ that significantly increases right ventricular contraction, relaxation, and heart rate.
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