Potentiation of the contractile effects of norepinephrine by hypoxia.
Hypoxia has been found to depress the concentration response curve of norepinephrine (NE) in isoalted cat papillary muscles. To investigate the effects of hypoxia in intact hearts, a heart-lung preparation was developed and maximum left ventricular dp/dt (max dp/dt) was measured at constant heart rate, preload, and after load. Left main coronary arterial flow (Q(e)) was measured with an electromagnetic flow probe. As arterial P(O2) decreased from 90 mm Hg (96% saturation) to 20-25 mm Hg (40% saturation) at constant P(CO2) and pH, no change in max dp/dt occurred and Q(e) increased 298%. In contrast to cat papillary muscles, the contractile responses to NE were augmented in hypoxia. The NE dose-response curves shifted to the left. No deterioration of contractility occurred after exposure to NE. In contrast, the chronotropic response was unaltered in hypoxia. Dose-response curves to isoproterenol also were shifted to the left in hypoxia, but responses to paired pacing were unchanged. The responses to NE under oxygenated conditions were unaltered by mechanically increased coronary flow or by increased coronary flow with nitroglycerin. Although the mechanisms responsible for these effects are unknown, the results suggest that hypoxia may open previously nonfunctioning vascular channels and thereby allow more extensive exposure of beta adrenergic receptors to circulating catecholamines.
D000818:Animals; D001011:Aorta; D001783:Blood Flow Velocity; D001794:Blood Pressure; D002245:Carbon Dioxide / Q000097:blood; D003326:Coronary Circulation / Q000187:drug effects; D004285:Dogs; D004558:Electric Stimulation; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects; D006400:Hematocrit; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia / Q000503:physiopathology*; D007275:Injections, Intravenous; D007545:Isoproterenol / Q000494:pharmacology; D008722:Methods; D005996:Nitroglycerin / Q000494:pharmacology; D009638:Norepinephrine / Q000008:administration & dosage / Q000494:pharmacology*; D010100:Oxygen / Q000097:blood; D010477:Perfusion
D002245:Carbon Dioxide; D005996:Nitroglycerin; D007545:Isoproterenol; D010100:Oxygen; D009638:Norepinephrine