Effect of Vasoactive Intestinal Peptide on Myocardial Contractility and Coronary Blood Flow in the Dog

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Abstract
The effects of intracoronary injections of vasoactive intestinal peptide (VIP) on left ventricular (LV) dp/dt, coronary blood flow (CBF), and myocardial oxygen consumption (M.ovrhdot.VO2) were compared with isoproterenol (ISO) and forskolin in 18 dogs using a preparation in which cardiac output, mean systemic arterial pressure, and heart rate were fixed. In eight dogs in which the effects of VIP and ISO were compared using doses ranging from 2 .times. 10-12 to 2 .times. 10-8 mol, both agents significantly increased LV dp/dt at doses .gtoreq. 6.6 .times. 10-10 mol. At maximum doses (2 .times. 10-9 to 2 .times. 10-8 mol) the effect of ISO was significantly greater than VIP. Both VIP and ISO significantly increased CBF at all doses, but at maximal doses the effect of VIP on CBF was significantly greater than ISO. The increase in CBF relative to the increase in M.ovrhdot.VO2, an index of direct coronary vasodilation, was significantly greater for VIP compared with ISO. In 10 additional dogs the effects of VIP and ISO were compared with forskolin given in doses ranging from 2 .times. 10-9 to 2 .times. 10-7 mol. At maximal doses (2 .times. 120-7 mol) the increase in LV dp/dt was similar to VIP but significantly less than ISO, whereas the increase in CBF was similar to ISO but significantly less than VIP. The increase in CBF relative to the increase in M.ovrhdot.VO2 was significantly greater for forskolin compared with ISO, indicating a direct vasodilator effect. These data indicate that VIP has a greater coronary vasodilator/inotropic ratio than either ISO or forskolin, agents that also activate the adenylate cyclase pathway. This distribution of the VIP effects may confer favorable therapeutic properties on agents that activate the VIP receptor pathway.