Differential modulation of nitric oxide and prostacyclin release in senescent rat heart stimulated by angiotensin II

Eur J Pharmacol. 1999 Oct 1;382(1):19-26. doi: 10.1016/s0014-2999(99)00575-0.


To elucidate the mechanism of age-related changes in the cardiovascular function stimulated with angiotensin II, we examined the effects of angiotensin II on the coronary flow, production of nitric oxide (NO) and prostacyclin, and on the cardiac function in the Langendorff-perfused young and aged rats' hearts. Angiotensin II decreased coronary flow, left ventricular dP/dt and heart rate. These effects were more pronounced in aged rats. Pretreatment with a NO synthase inhibitor, N(G)-nitro-L-arginine, significantly increased the angiotensin II-induced vasoconstriction in young rats. Angiotensin II increased the concentration of NO in the coronary effluent in young but not in aged rats. In contrast, angiotensin II stimulated the release of prostacyclin to a much greater extent in aged rats than in young rats. These results suggest that impaired production of NO may contribute to the greater constrictor effect of angiotensin II in the aged rat, although aging modulated the production of prostacyclin in a different manner. This age-related endothelial dysfunction may alter the physiological regulation of coronary flow and cardiac function stimulated with angiotensin II.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Aging / physiology*
  • Angiotensin II / pharmacology*
  • Angiotensin II / physiology
  • Animals
  • Atrial Natriuretic Factor / biosynthesis
  • Coronary Circulation / drug effects*
  • Drug Interactions
  • Endothelium, Vascular / physiology
  • Enzyme Inhibitors / pharmacology
  • Epoprostenol / biosynthesis*
  • Heart / drug effects
  • Heart / physiology
  • In Vitro Techniques
  • Male
  • Nitric Oxide / biosynthesis*
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitroarginine / pharmacology
  • Perfusion
  • Rats
  • Rats, Inbred F344
  • Time Factors
  • Vasoconstriction / drug effects


  • Enzyme Inhibitors
  • Angiotensin II
  • Nitroarginine
  • Nitric Oxide
  • Atrial Natriuretic Factor
  • Epoprostenol
  • Nitric Oxide Synthase
  • Acetylcholine