Endothelium-dependent vasodilating effect of substance P during flow-reducing coronary stenosis in the dog.
The effects of substance P, a putative central and peripheral neurotransmitter, on coronary vasculature and its mechanisms were studied in 31 anesthetized open chest dogs. Without coronary stenosis, intracoronary infusion of substance P (0.001 to 1 pmol/kg per min) for 40 s increased coronary blood flow up to 173 +/- 10.7% in dose-dependent fashion. Application of coronary stenosis created by an inflated intraluminal microballoon that preserved active vasomotion of the stenosed segment produced a pressure gradient of 34 +/- 2 mm Hg, a decrease in rest coronary blood flow of 21 +/- 1.6% and significant depression of the rate of rise in left ventricular pressure (dP/dt). During coronary stenosis, substance P increased coronary blood flow up to 150 +/- 9.4%, lowered mean distal coronary pressure and decreased stenosis resistance in dose-dependent fashion. After endothelial denudation of the proximal part of the coronary artery, the substance P-induced increments in coronary blood flow during coronary stenosis were abolished. In vitro measurements of isometric tension from both intact and denuded portions of coronary arteries confirmed a marked inhibition of substance P-induced relaxation in the denuded segments. These results show the obligatory role of the endothelium in substance P-induced coronary artery dilation. Furthermore, intracoronary infusion of substance P (1 pmol/kg per min) from the site distal to coronary stenosis that precluded the responsiveness of the large coronary artery decreased coronary blood flow by 24 +/- 4%, lowered mean distal coronary pressure by 15 +/- 1.9 mm Hg and intensified stenosis resistance by 77 +/- 7.2%. Thus, substance P exerts a direct potent dilating effect on both large and small coronary arteries. However, because of its strict endothelium-dependency, this peptide may play a detrimental role in the regulation of coronary blood flow when an atherosclerotic stenotic lesion with endothelial damage or dysfunction is present in the proximal part of the coronary artery.
First Department of Internal Medicine, Kobe University School of Medicine, Japan.
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Yatani
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Yokoyama
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Akita
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Fukuzaki
D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D003326:Coronary Circulation / Q000502:physiology*; D003327:Coronary Disease / Q000503:physiopathology*; D003331:Coronary Vessels / Q000473:pathology / Q000502:physiology; D004285:Dogs; D004730:Endothelium, Vascular / Q000473:pathology / Q000502:physiology*; D005260:Female; D066298:In Vitro Techniques; D007261:Infusions, Intra-Arterial; D008297:Male; D005996:Nitroglycerin / Q000494:pharmacology; D013373:Substance P / Q000502:physiology*; D014664:Vasodilation / Q000502:physiology*
D013373:Substance P; D005996:Nitroglycerin