Role of intact cardiac nerves and reflex mechanisms in desensitization to catecholamines in conscious dogs.
To study chronic catecholamine desensitization, mini-osmotic pumps were implanted subcutaneously to deliver NE, (0.5 micrograms/kg/min) or saline over 3-4 wk in dogs instrumented with left ventricular (LV) pressure gauges and arterial and left atrial pressure catheters. An acute challenge to NE (0.4 micrograms/kg/min) in intact, conscious dogs increased LV dP/dt by 1,531 +/- 208 mmHg/s before NE pumps, and by a similar amount, 1,340 +/- 166 mmHg/s, 3-4 wk after NE pumps. In contrast, an acute challenge to isoproterenol (ISO, 0.4 micrograms/kg/min) increased LV dP/dt by 5,344 +/- 532 mmHg/s before NE pumps, and significantly less (P less than 0.05; 2,425 +/- 175 mmHg/s) after NE pumps. In the presence of ganglionic and alpha 1-adrenergic blockades, NE (0.4 micrograms/kg/min) increased LV dP/dt by 3,656 +/- 468 mmHg/s before NE pumps and significantly less (P less than 0.01; 1,459 +/- 200 mmHg/s) after NE pumps. Confirming this, an acute challenge to NE (0.4 micrograms/kg/min) in dogs with arterial baroreceptor denervation increased LV dP/dt by 3,732 +/- 896 mmHg/s before NE pumps, and significantly less (P less than 0.05, 1,725 +/- 408 mmHg/s) after NE pumps. In addition, in cardiac denervated dogs, NE (0.4 micrograms/kg/min) increased LV dP/dt by 9,901 +/- 1,404 mmHg/s before NE pumps and significantly less (P less than 0.01, 2,690 +/- 306 mmHg/s) after NE pumps. Desensitization of heart rate responses to NE challenge was also more apparent in the absence of reflex mechanisms. Thus, neural reflex mechanisms play a major role in physiological expression of cardiac desensitization to catecholamines in conscious dogs.
Nejima
J
J
Department of Medicine, Harvard Medical School, Brigham & Women's Hospital, Boston, Massachusetts 02115.
Uemura
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Vatner
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Homcy
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Hintze
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Vatner
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D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D006321:Heart / Q000294:innervation*; D006339:Heart Rate / Q000187:drug effects*; D007545:Isoproterenol / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects*; D009638:Norepinephrine / Q000008:administration & dosage*; D011311:Pressoreceptors / Q000502:physiology; D012018:Reflex / Q000502:physiology; D014851:Wakefulness
D007545:Isoproterenol; D009638:Norepinephrine