SUPPRESSION BY ETHANOL OF PRESSOR-RESPONSE CAUSED BY THE INHIBITION OF NITRIC-OXIDE SYNTHESIS

The effects of ethanol on mean arterial pressure (MAP) and heart rate (HR) responses to the nitric oxide svnthase inhibitor, N(G)-nitro-L-arginine, and to angiotensin II and noradrenaline were studied in rats. I.V. bolus injections of N(G)-nitro-L-arginine dose dependently increased MAP in vehicle-pretreated rats, with a maximum increase of 56 +/- 7 mm Hg and an ED50 of 3.8 +/- 0.4 mg/kg, respectively. I.v. infusions of ethanol dose dependently reduced maximum MAP response to N(G)-nitro-L-arginine, with a K(i) of 96 +/- 8 mg/kg per min but did not alter the ED50. Ethanol (48 mg/kg per min) did not modify the MAP response to i.v. bolus injections of angiotensin II (0.02-1.28 mug/kg) or noradrenaline (0.25-16 mug/kg). However, ethanol attenuated the reflex HR responses of N(G)-nitro-L-arginine and angiotensin II but not that of noradrenaline. The results demonstrate that ethanol selectively but non-competitively inhibits the MAP response to N(G)-nitro-L-arginine, suggesting an interaction between ethanol and the L-arginine/nitric oxide pathway.