ASSESSMENT OF ABILITY OF LEVCROMAKALIM AND SODIUM-NITROPRUSSIDE TO REVERSE THE CARDIOVASCULAR EFFECTS OF NITRIC-OXIDE SYNTHASE INHIBITION IN THE ANESTHETIZED PIG

Objective: The aim was to test the ability of levcromakalim, a potassi um channel opener, and sodium nitroprusside, a nitric oxide donor, to reverse the systemic and pulmonary vasoconstrictor actions of N-G-nitr o-L-arginine methyl ester (L-NAME), and thus to restore cardiac output in anaesthetised pigs. Methods: In separate groups of pigs administra tion of a bolus of L-NAME (10 mg.kg(-1)) was followed either by no fur ther agent (control group; n = 8) or by increasing bolus doses of levc romakalim (10, 20, and 40 mu g.kg(-1); n = 8) or by increasing infused doses of sodium nitroprusside (1, 2, and 4 mu g.kg(-1).min(-1) for 15 min at each dose). The same doses of levcromakalim and sodium nitropr usside were also given to pigs (n = 6 in each group) which had been ge s in systemic and pulmonary haemodynamic indices and cardiac output as a result of each intervention were measured at each stage and compare d between and within drug groups. Results: In each group, the bolus of L-NAME caused increases in systemic vascular resistance, mean arteria l pressure, pulmonary vascular resistance, and mean pulmonary artery p ressure, and a reduction in were significantly different from pretreat ment values at 15 min, and were maintained for at least 60 min when no further agent was given. The subsequent administration of levcromakal im caused significant reductions in systemic vascular resistance and m ean arterial pressure, the effects being than in animals that had been pretreated with saline rather than L-NAME. Pulmonary vascular resista nce and mean pulmonary artery pressure were also reduced, but to a les ser degree. Cardiac output was partially but significantly restored. T he subsequent administration of sodium nitroprusside caused significan t reductions in systemic vascular resistance, mean arterial pressure, pulmonary vascular resistance, and mean pulmonary artery pressure. The se effects were significantly greater than those in animals that had b een pretreated with saline rather than L-NAME. Cardiac output was weak ly, though significantly restored. Conclusions: Increased systemic vas cular resistance following a bolus of L-NAME (10 mg.kg(-1)) is reverse d by subsequent administration of levcromakalim (10-40 mu g.kg(-1)) or sodium nitroprusside (1-4 mu g.kg(-1).min(-1)) associated with partia l restoration of cardiac output. The degree to which cardiac output is restored by these two agents is limited by a concomitant reduction in preload.