Presence and actions of vasoactive intestinal peptide in the isolated rabbit heart.
The objectives of these experiments were to localize vasoactive intestinal peptide immunoreactivity (VIP-IR) in the intracardiac ganglia of the interatrial septum of the rabbit heart and to examine the effects of vasoactive intestinal peptide (VIP) on the isolated perfused rabbit heart. Cell bodies of neurones containing VIP-IR were located in the interatrial septa of rabbit hearts by using immunocytochemistry. In addition, the effects of substance P (SP), neurokinin A (NKA), and neurokinin B (NKB) on the isolated rabbit heart were compared with those of VIP. Bolus injections of SP, NKA, VIP, and NKB caused dose-dependent decreases in the perfusion pressure of hearts perfused at constant flow with ED50 values of 2.73 +/- 0.10 fmol (n = 6), 0.18 +/- 0.01 pmol (n = 8), 93.75 +/- 1.88 pmol (n = 6), and 75.00 +/- 3.06 pmol (n = 6), respectively. The slope of the dose-response curve of VIP was much greater than those of SP and NKA, suggesting the presence of one receptor subtype for VIP and multiple receptor subtypes for the neurokinins on rabbit coronary vessels. Differences in the slopes of the dose-response curves and potency may reflect differences in the mechanism of vasodilatation. The maximal values of vasodilatation of all of the peptides did not differ. None of the peptides produced significant changes in heart rate, left ventricular pressure, or contractility. These results suggest that VIP found in the intracardiac neurones of the rabbit heart can mediate coronary vasodilatation.
Accili
E A
EA
Department of Physiology, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
Buchan
A M
AM
Kwok
Y N
YN
Ledsome
J R
JR
Brown
J C
JC
D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D005724:Ganglia / Q000187:drug effects / Q000378:metabolism; D006321:Heart / Q000187:drug effects* / Q000294:innervation; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D015288:Neurokinin A / Q000494:pharmacology; D015287:Neurokinin B / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects; D011817:Rabbits; D013373:Substance P / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism* / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects
D013373:Substance P; D014660:Vasoactive Intestinal Peptide; D015288:Neurokinin A; D015287:Neurokinin B