VASODILATORY EFFECTS OF KETAMINE ON PULMONARY-ARTERIES IN RATS WITH CHRONIC HYPOXIC PULMONARY-HYPERTENSION

To study the effects of ketamine on structurally remodeled pulmonary a rteries from rats with hypoxic pulmonary hypertension (PH) and the eff ects of ketamine on endothelium-dependent and -independent relaxation, rats were exposed to hypobaric hypoxia (air at 380 mm Hg for 10 days) . We measured the responses to ketamine, acetylcholine, and sodium nit roprusside (SNP) in prostaglandin F-2 alpha-precontracted ring segment s from a left extrapulmonary artery (EPA, 1.4-1.6 mm in outside diamet er [OD]) and an intrapulmonary artery (IPA, 0.7-1.1 mm OD) obtained fr om control and PH rats. The effects of acetylcholine and SNP were decr eased in EPA and IPA rings from PH rats compared with control rings. I n contrast, ketamine produced a greater relaxation response in rings f rom PH rats at 3 X 10(-5)-3 x 10(-4) in the EPA and at 10(-4)-10(-3) M in the IPA compared to control rings. A nitric oxide synthase inhibito r, nitro-L-arginine (10(-4) M), inhibited the relaxation in response t o acetylcholine in both control and PH rats. Pretreatment with ketamin e (10(-4) M) had no effect on the relaxation response to any concentra tion of acetylcholine or SNP in either control or PH rats. We conclude that nitric-oxide-mediated relaxation, but not ketamine-induced relax ation, was impaired in structurally remodeled hypertensive pulmonary a rteries. Ketamine had no effects on nitric oxide-mediated relaxation i n either normal or PH rats.