Neuropeptide-Y: a peptide found in human coronary arteries constricts primarily small coronary arteries to produce myocardial ischemia in dogs

• Published in: The Journal of clinical investigation 1989-04, Vol.83 (4), p.1217-1224
• Main Authors: MATURI, M. F, GREENE, R, SPEIR, E, BURRUS, C, DORSEY, L. M. A, MARKLE, D. R, MAXWELL, M, SCHMIDT, W, GOLDSTEIN, S. R, PATTERSON, R. E
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cardiology. Vascular system; Coronary Circulation - drug effects; Coronary Disease - etiology; Coronary Disease - metabolism; Coronary heart disease; Coronary Vessels - analysis; Coronary Vessels - drug effects; Coronary Vessels - physiology; Dogs; Heart; Heart Rate - drug effects; Humans; Hydrogen-Ion Concentration; Injections, Intra-Arterial; ischemia; Medical sciences; neuropeptide Y; Neuropeptide Y - administration & dosage; Stroke Volume - drug effects; Vascular Resistance - drug effects; Vasoconstrictor Agents - administration & dosage
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/JCI114004

Neuropeptide-Y (NPY), a brain peptide, is located in the walls of human coronary arteries. This study assessed the effects of NPY on the coronary circulation in 40 chloralose-anesthetized, open-chest dogs. Intracoronary NPY (42 nmol over 5.2 min) caused a 39% reduction in coronary blood flow without changing heart rate or aortic pressure. To determine whether this vasoconstriction could produce ischemia, intramyocardial pH was measured in seven dogs (group I) and decreased from 7.45 +/- 0.06 to 7.37 +/- 0.06 pH units after NPY in the subendocardium (P less than 0.0002), and from 7.45 +/- 0.06 to 7.40 +/- 0.05 pH units (P less than 0.04) in the subepicardium of the infused zone. Left ventricular ejection fraction (LVEF), measured by radionuclide angiography, decreased from 0.52 +/- 0.08 to 0.42 +/- 0.12 U (n = 5, P less than 0.01) during NPY. NPY-induced vasoconstriction was also associated with ST-T wave changes on the electrocardiogram (ECG) in eight of nine other animals (group V). In another group of six dogs (group IV), the change in small vessel resistance accounted for 94% of the increase in total resistance, so that the primary vasoconstrictor effect of NPY was exerted on small coronary arteries. Thus, NPY, a peptide found in human coronary arteries, caused constriction of primarily small coronary arteries that was severe enough to produce myocardial ischemia as determined by ECG ST-T wave changes, and decreases in intramyocardial pH and LVEF in dogs.