Coronary vascular responses to hypoxia in the diabetic lamb: independence from adenosine and autonomic mechanisms.
We have previously found that the coronary dilator response to infused adenosine is attenuated in diabetic (alloxan) lambs. Adenosine responsiveness is restored by administration of insulin. The present studies tested the hypothesis that coronary flow changes with hypoxia, if mediated by adenosine, would also be modified. Studies were carried out in eight control and six diabetic lambs. The animals were anesthetized and prepared to maintain constant arterial pressure (reservoir), cardiac output (pump), and heart rate (paced). Atropine and practolol were given. Forced inspired oxygen was reduced in steps. Arterial and coronary sinus blood samples were analyzed for Po2, oxygen content, pH, hematocrit, and glucose. Myocardial oxygen delivery and uptake (MVO2) were calculated. Coronary flow increased identically in both control and diabetic animals as PaO2 was reduced below 60 Torr. Oxygen delivery and MVO2 fell equally in both groups. Acidosis potentiated hypoxic coronary flow changes. Alpha blockade (phentolamine) was without effect in control lambs but caused coronary flow to increase in diabetic lambs. Changes in coronary flow with hypoxia were unaffected, however. Insulin caused no change in the coronary dilator response to hypoxia in either control or diabetic lambs. It is concluded that coronary alpha tone is increased in diabetes but does not modify changes in coronary flow during hypoxia. As coronary flow responses to hypoxia were unaltered in diabetic lambs, and unaffected by insulin, adenosine may not be the primary mediator of coronary vascular dilatation. Potentiation of adenosine by tissue acidosis is apparently insufficient to explain these findings. The mechanism for coronary dilatation during hypoxia is unclear but may involve direct effects of reduced oxygenation of coronary vascular smooth muscle.
D000138:Acidosis / Q000503:physiopathology; D000241:Adenosine / Q000502:physiology*; D000818:Animals; D002302:Cardiac Output; D003326:Coronary Circulation; D003331:Coronary Vessels / Q000503:physiopathology*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000503:physiopathology*; D005260:Female; D006339:Heart Rate; D000860:Hypoxia / Q000503:physiopathology*; D007328:Insulin / Q000627:therapeutic use; D007773:Lactates / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption; D010646:Phentolamine / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D012756:Sheep; D014664:Vasodilation
D007328:Insulin; D007773:Lactates; D011942:Receptors, Adrenergic, alpha; D000241:Adenosine; D010646:Phentolamine