Modulation of adrenergic contraction of dog pulmonary arteries by nitric oxide and prostacyclin

Gen Pharmacol. 1999 May;32(5):583-9. doi: 10.1016/s0306-3623(98)00285-7.

Abstract

The aim of this work was to investigate the influence of endothelium-derived nitric oxide and prostaglandins on the contractile responses of isolated dog pulmonary arteries to electrical field stimulation and noradrenaline. Electrical field stimulation (1-8 Hz, 20 v, 0.25 ms duration, for 30 s) produced frequency-dependent contractions that were abolished by tetrodotoxin, guanethidine and, prazosin (all at 10(-6) M). Noradrenaline induced concentration-dependent contractions with an EC50, of 1.85 x 10(-6) M. The increases in tension induced by electrical stimulation and noradrenaline were of greater magnitude in arteries denuded of endothelium. In segments with endothelium, N(G)-nitro-L-arginine methyl ester (10(-4) M) or indomethacin (10(-5) M) had no effects on the basal tone, but significantly enhanced the neurogenic and noradrenaline-induced contractions. The potentiation by N(G)-nitro-L-arginine methyl ester of electrical stimulation-induced contractile responses was partially reversed by L-arginine (10(-4) M). In the presence of N(G)-nitro-L-arginine methyl ester together with indomethacin the electrical stimulation-induced contractile responses were higher than those obtained when only N(G)-nitro-L-arginine methyl ester or indomethacin was used. N(G)-nitro-L-arginine methyl ester and indomethacin did not influence neurogenic-induced contractile responses of endothelium-denuded arteries. The results suggest that endothelial cells of isolated dog pulmonary arteries depress the contractile response to electrical field stimulation of intramural nerves and that endothelium-derived dilator prostaglandins and nitric oxide may interact to inhibit contractile effects of adrenergic stimulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antihypertensive Agents / pharmacology*
  • Cyclooxygenase Inhibitors / pharmacology
  • Dogs
  • Drug Interactions
  • Electric Stimulation
  • Enzyme Inhibitors / pharmacology
  • Epoprostenol / pharmacology*
  • Female
  • In Vitro Techniques
  • Indomethacin / pharmacology
  • Male
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide / metabolism*
  • Norepinephrine / pharmacology
  • Prostaglandins / metabolism
  • Pulmonary Artery / drug effects*
  • Pulmonary Artery / physiology
  • Vasoconstriction / drug effects*

Substances

  • Antihypertensive Agents
  • Cyclooxygenase Inhibitors
  • Enzyme Inhibitors
  • Prostaglandins
  • Nitric Oxide
  • Epoprostenol
  • NG-Nitroarginine Methyl Ester
  • Norepinephrine
  • Indomethacin