SELECTIVE-INHIBITION OF PRESSOR AND HEMODYNAMIC-EFFECTS OF N(G)-NITRO-L-ARGININE BY HALOTHANE

We investigated the characteristics of inhibition by halothane of the pressor responses to N(G)-substituted L-arginine derivatives, nitric o xide (NO) synthase inhibitors. Intravenous (i.v.) bolus injections of N(G)-nitro-L-arginine (L-NNA, 1-32 mg/kg), N(G)-nitro-L-arginine methy l ester (L-NAME, 0.4-12.8 mg/kg), norepinephrine (NE, 0.25-8 mug/kg) a nd angiotensin II (AII, 0.02-0.64 mug/kg) each caused dose-dependent p ressor responses in conscious rats. Halothane attenuated responses to the highest dose of NE and All by approximately 18% but completely abo lished responses to L-NNA and L-NAME. The haemodynamic effects of L-NN A 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 redu ced heart rate (HR) and cardiac output (CO). These changes were associ ated with reduced conductance in all vascular beds, with the greatest reduction in the lungs and the least in the liver. In halothane-anaest hetized rats, L-NNA caused significant but markedly less change in MAP , HR, TPR, and CO as compared with those in conscious rats. The vasoco nstrictor effects of L-NNA were attenuated by halothane in all beds ex cept liver and spleen, with the greatest inhibition in heart. Our resu lts suggest that NO plays a role in maintenance of peripheral vascular resistance and that halothane selectively and ''noncompetitively'' in hibits the vasoconstrictor effects of NO synthase inhibitors.