The effects of right cervical vagal and left sympathetic stimulation on release of immunoreactive vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY) into cardiac venous and lymphatic effluent was tested in 11 anesthetized adult mongrel dogs. After stimulation of the right cervical vagus (1 ms, 20 Hz, 5 V) for 3 min, VIP output in lymphatic effluent was significantly increased at 1.90 +/- 0.56 pg/min compared with control of 0.90 +/- 0.42 pg/min. NPY output in lymphatic effluent and VIP and NPY release into coronary venous effluent, as measured by the arterial-coronary sinus concentration difference, were not changed. After stimulation of the ansae of the left sympathetic ganglion (1 ms, 10 Hz, 5 V) for 3 min, NPY output in lymphatic effluent was significantly increased at 4.72 +/- 1.58 pg/min compared with a control of 0.73 +/- 0.66 pg/min. VIP output in lymphatic effluent was not changed. VIP arterial-coronary sinus concentration difference decreased slightly but significantly, and NPY arterial-coronary sinus concentration difference decreased markedly after left sympathetic stimulation. In three additional dogs in which coronary sinus blood flow was measured, NPY overflow during left sympathetic stimulation increased from 28.2 +/- 23.5 to 129.6 +/- 212.7 pg/min. Thus VIP and NPY release from the canine heart can be evoked by right cervical vagal and left sympathetic stimulation, respectively. VIP and NPY may play a role as cardiac noncholinergic-nonadrenergic neurotransmitters.
Desensitization to the hemodynamic effects of vasoactive intestinal polypeptide (VIP) was examined in 12 anesthetized, open-chest dogs in which cardiac output, systemic arterial resistance, and heart rate were fixed. VIP was administered by intracoronary infusion, and the effects were compared with isoproterenol and forskolin. Measurements of left ventricular maximum rate of pressure development (dP/dt), coronary blood flow, and myocardial oxygen consumption were made before and after a 90-min infusion of either isoproterenol (6 dogs) or VIP (6 dogs). After isoproterenol infusion, there was a significant decrease in the effect of isoproterenol on left ventricular dP/dt and coronary blood flow. The effects of VIP and forskolin were not changed. After VIP infusion, there was a significant decrease in the effect of VIP on left ventricular dP/dt with no change in the effects of isoproterenol and forskolin. In this group, a significant increase in coronary blood flow with minimal change in myocardial oxygen could still be elicited by VIP injection after VIP infusion. The agonist infusion time to achieve a decrease in inotropic effect was less for VIP when compared with isoproterenol. Thus these data demonstrate acute homologous desensitization of myocardial VIP and beta-adrenergic receptors in canine myocardium with no development of heterologous desensitization, desensitization involving the catalytic subunit of adenylate cyclase, or desensitization of the VIP-mediated primary coronary vasodilator response.
The effect of total cardiac denervation on the distribution of cardiac immunoreactive vasoactive intestinal peptide (IR-VIP) was determined in four groups of dogs. Denervated dogs killed at either 7 days (group 1) or 30 days (group 3) were compared with sham-operated dogs killed at either 7 days (group 2) or 30 days (group 4). The highest concentrations of IR-VIP were found in the left atrium and proximal left anterior descending and circumflex coronary arteries and were not affected by denervation. Concentrations of IR-VIP in the left ventricle were barely detectable. Only right ventricular IR-VIP concentrations were significantly lower in denervated compared with sham-operated dogs in both groups. Thus these data provide evidence of intrinsic VIP innervation of the atria and epicardial coronary arteries and localized extrinsic VIP innervation of the right ventricle of the canine heart.
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