SYMPATHETIC MODULATION OF ENDOTHELIUM-DERIVED RELAXING FACTOR

To determine whether the release of endothelium-derived relaxing factor (EDRF) is sympathetically mediated, we studied the effects of beta-blockade by propranolol, ganglionic blockade with hexamethonium, or mechanical pithing on the blood pressure response to EDRF inhibition in anesthetized rats. We inhibited EDRF with 10 mg/kg of either N(G)-monomethyl-L-arginine (L-NMMA) or N(omega)-nitro-L-arginine-methyl ester (L-NAME). In controls, L-NMMA and L-NAME increased blood pressure by 14+/-1 (p<0.01) and 22+/-2 mm Hg (p<0.01), respectively. Propranolol lowered blood pressure from 98+/-3 to 72+/-4 mm Hg without altering the response to L-NAME (DELTA-26 +/- 3). This response correlated with the resting blood pressure (r=0.87; p<0.001). Hexamethonium (25 mg/kg) lowered blood pressure from 118+/-6 to 85+/-4 mm Hg but did not change the response to L-NMMA (DELTA-15+/-1). In pithed rats, blood pressure was lowered, but the pressor response to L-NAME was unchanged. When blood pressure was returned to normotensive levels by angiotensin II, norepinephrine, or phenylephrine, L-NAME increased blood pressure by 50+/-2, 68+/-8, and 109+/-7 mm Hg, respectively (p<0.001). We conclude that an intact autonomic nervous system is not needed for the pressor response to EDRF inhibition. The enhanced response in pithed rats treated with vasoconstrictors may be due to removal of the buffering effect of the baroreceptors and the absence of EDRF, which would oppose vasoconstriction. The correlation between blood pressure and the L-NAME response in the propranolol group may be due to the degree of preconstriction of the peripheral arterioles or to a direct relation between blood pressure and EDRF. The greater response to EDRF synthesis inhibition observed in the rats pretreated with phenylephrine suggests that EDRF synthesis may be stimulated by alpha-1-receptors.