title: Cholesterol potentiates the coronary artery response to norepinephrine in anesthetized and conscious dogs.
abstract: We investigated the effect of hypercholesterolemia on coronary and cardiac hemodynamic responses to intracoronary norepinephrine (NE) (0.01 to 10.0 micrograms/min as the bitartrate) in a Gregg cannula autoperfusion system. Coronary blood flow was measured by the radioactive microsphere technique in two groups of open-chest dogs anesthetized with pentobarbital: 10 controls and 8 that were fed a cholesterol-rich diet (CD) which doubled the serum cholesterol level. In the control dogs, NE in doses of 0.01 to 1.0 micrograms/min had no effect on coronary vascular resistance (CVR) but 10 micrograms/min caused a significant decrease to 0.58 +/- 0.12 of control. In the CD dogs, NE at doses of 1.0 and 10.0 micrograms/min significantly reduced CVR, to 0.72 +/- 0.06 and 0.52 +/- 0.11 of control, respectively. There was no consistent effect of NE, at these doses, on myocardial oxygen uptake, left ventricular stroke work index, or maximal positive dP/dt. In a second series of experiments we measured coronary flow with electromagnetic flowmeters in 11 chronically instrumented conscious dogs, 5 controls, and 6 CD. In the control dogs, intravenously administered NE hydrochloride, 0.01 microgram/min, reduced CVR to 0.74 +/- 0.07 of control, and 1.0 microgram/min increased CVR to 1.26 +/- 0.09 of control. In the CD animals, these effects were seen at a 10-fold lower NE dose, 0.001 microgram/min (0.83 +/- 0.11 of control) and 0.1 microgram/min (1.32 +/- 0.06 of control). The vasodilation was blocked by propranolol, and vasoconstriction by phentolamine. We conclude that NE at low doses activates beta-adrenoreceptors to reduce CVR and at higher doses activates alpha-adrenoreceptors to increase CVR; the vasoconstrictor response is inhibited in pentobarbital anesthetized dogs, and hypercholesterolemia sensitizes coronary vessels to both the dilator and constrictor effects of NE.
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002784:Cholesterol / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects*; D003331:Coronary Vessels / Q000187:drug effects / Q000294:innervation; D004285:Dogs; D004357:Drug Synergism; D006339:Heart Rate / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects; D010477:Perfusion; D014655:Vascular Resistance; D014666:Vasomotor System / Q000187:drug effects*
chemical_list: D000319:Adrenergic beta-Antagonists; D002784:Cholesterol; D009638:Norepinephrine