Cholesterol Potentiates the Coronary Artery Response to Norepinephrine in Anesthetized and Conscious Dogs

• Published in: Circulation research 1981-03, Vol.48 (3), p.320-329
• Main Authors: ROSENDORFF, CLIVE, HOFFMAN, JULIEN I.E, VERRIER, EDWARD D, ROULEAU, JACQUES, BOERBOOM, LAWRENCE E
• Format: Article
• Language: English
• Subjects: Adrenergic beta-Antagonists - pharmacology; Animals; Blood Pressure - drug effects; Cardiac Output - drug effects; Cholesterol - pharmacology; Coronary Circulation - drug effects; Coronary Vessels - drug effects; Coronary Vessels - innervation; Dogs; Drug Synergism; Heart Rate - drug effects; Myocardium - metabolism; Norepinephrine - pharmacology; Oxygen Consumption - drug effects; Perfusion; Vascular Resistance; Vasomotor System - drug effects
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/01.res.48.3.320

We investigated the effect of hypercholesterolemia on coronary and cardiac hemody- namic responses to intracoronary norepinephrine (NE) (0.01 to 10.0 /μg/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 pentobarbital10 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 /μg/min had no effect on coronary vascular resistance (CVR) but 10 /μg/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 /μg/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 /μg/min, reduced CVR to 0.74 ± 0.07 of control, and 1.0 /μg/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 /μg/min (0.83 ± 0.11 of control) and 0.1 /μg/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 /β-adrenoreceptors to reduce CVR and at higher doses activates a-adrenoreceptors to increase CVR; the vasoconstrictor response is inhibited in pentobarbital anesthe- tized dogs, and hypercholesterolemia sensitizes coronary vessels to both the dilator and constrictor effects of NE. CircRes 48320-329, 1981