Selective inhibition of pressor and haemodynamic effects of NG-nitro-L-arginine by halothane.
We investigated the characteristics of inhibition by halothane of the pressor responses to NG-substituted L-arginine derivatives, nitric oxide (NO) synthase inhibitors. Intravenous (i.v.) bolus injections of NG-nitro-L-arginine (L-NNA, 1-32 mg/kg), NG-nitro-L-arginine methyl ester (L-NAME, 0.4-12.8 mg/kg), norepinephrine (NE, 0.25-8 micrograms/kg) and angiotensin II (AII, 0.02-0.64 micrograms/kg) each caused dose-dependent pressor responses in conscious rats. Halothane attenuated responses to the highest dose of NE and AII by approximately 18% but completely abolished responses to L-NNA and L-NAME. The haemodynamic effects of L-NNA were further examined by the microsphere technique in two groups of conscious rats and two groups of halothane-anaesthetized rats. An i.v. bolus injection of L-NNA (16 mg/kg) in conscious rats increased mean arterial pressure (MAP) and total peripheral resistance (TPR) and reduced heart rate (HR) and cardiac output (CO). These changes were associated with reduced conductance in all vascular beds, with the greatest reduction in the lungs and the least in the liver. In halothane-anaesthetized rats, L-NNA caused significant but markedly less change in MAP, HR, TPR, and CO as compared with those in conscious rats. The vasoconstrictor effects of L-NNA were attenuated by halothane in all beds except liver and spleen, with the greatest inhibition in heart. Our results suggest that NO plays a role in maintenance of peripheral vascular resistance and that halothane selectively and "noncompetitively" inhibits the vasoconstrictor effects of NO synthase inhibitors.
Wang
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YX
Department of Pharmacology & Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
Abdelrahman
A
A
Pang
C C
CC
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000804:Angiotensin II / Q000037:antagonists & inhibitors; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors; D001794:Blood Pressure / Q000187:drug effects*; D002302:Cardiac Output / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006221:Halothane / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007275:Injections, Intravenous; D008863:Microspheres; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D009638:Norepinephrine / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D014655:Vascular Resistance / Q000187:drug effects
D000804:Angiotensin II; D019335:Nitroarginine; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D006221:Halothane; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine