Role of intact cardiac nerves and reflex mechanisms in desensitization to catecholamines in conscious dogs

J. Nejima, N. Uemura, D. E. Vatner, C. J. Homcy, T. H. Hintze, S. F. Vatner

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

To study chronic catecholamines desensitization, mini-osmotic pumps were implanted subcutaneously to deliver NE, (0.5 μg/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 μg/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 μg/kg/min) increased LV dP/dt by 5,344 ± 532 mmHg/s before NE pumps, and significantly less (P<0.05; 2,425 ± 175 mmHg/s) after NE pumps. In the presence of ganglionic and α1-adrenergic blockades, NE (0.4 μg/kg/min) increased LV dP/dt by 3,656 ± 468 mmHg/s before NE pumps and significantly less (P<0.01; 1,459 ± 200 mmHg/s) after NE pumps. Confirming this, an acute challenge to NE (0.4 μg/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<0.05, 1,725 ± 408 mmHg/s) after NE pumps. In addition, in cardiac denervated dogs, NE (0,4 μg/kg/min) increased LV dP/dt by 9,901 ± 1,404 mmHg/s before NE pumps and significantly less (P<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.

Original languageEnglish (US)
Pages (from-to)2046-2053
Number of pages8
JournalJournal of Clinical Investigation
Volume86
Issue number6
DOIs
StatePublished - 1990

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Keywords

  • arterial baroreceptor denervation
  • cardiac denervation
  • left ventricular function
  • norepinephrine
  • β-adrenergic receptors

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