INHIBITION OF NITRIC-OXIDE SYNTHESIS AUGMENTS CENTRALLY INDUCED SYMPATHETIC CORONARY VASOCONSTRICTION IN CATS

The principal effect of sympathetic activation on the coronary circula tion is an alpha-adrenergic coronary vasoconstriction in the presence of beta-receptor blockade. Secondary effects include vasodilation due to beta-adrenoceptor stimulation and alpha(2)-mediated release of endo thelium-derived relaxing factor (EDRF) from the coronary vascular endo thelium. We hypothesized that blockade of nitric oxide synthesis (nitr o-L-arginine methyl ester, L-NAME) would augment coronary vasoconstric tion to sympathetic stimulation as a result of a decrease in alpha(2)- mediated EDRF release. In chloralose-anesthetized cats, hypothalamic s timulation produced increases in coronary vascular resistance [maximum 26 +/- 9% (SE)] and arterial pressure (41 +/- 7%) and a decrease in c oronary blood flow velocity (15 +/- 6%). L-NAME (3 mg/kg iv) increased baseline arterial pressure from 69 +/- to 92 +/- 7 mmHg (P < 0.05). A fter L-NAME, a greater increase in coronary vascular resistance (55 +/ - 20%, P < 0.05), a decrease in coronary blood flow velocity (24 +/- 7 %, P < 0.05), and a similar presser response (34 +/- 7%) were observed in response to hypothalamic stimulation. L-Arginine reversed the effe ct of L-NAME on coronary vasoconstriction to hypothalamic stimulation. Similar increases in arterial pressure (from 73 +/- 3 to 91 +/- 5 mmH g, P < 0.05) with vasopressin (0.01-0.05 U/min) failed to enhance coro nary vasoconstriction to activation in anterior hypothalamus. We concl ude that inhibition of EDRF synthesis augments centrally induced sympa thetic coronary vasoconstriction in the cat.