Vasodilatory effects of ketamine on pulmonary arteries in rats with chronic hypoxic pulmonary hypertension.
To study the effects of ketamine on structurally remodeled pulmonary arteries from rats with hypoxic pulmonary hypertension (PH) and the effects 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 nitroprusside (SNP) in prostaglandin F2 alpha-precontracted ring segments from a left extrapulmonary artery (EPA, 1.4-1.6 mm in outside diameter [OD] and an intrapulmonary artery (IPA, 0.7-1.1 mm OD) obtained from control and PH rats. The effects of acetylcholine and SNP were decreased in EPA and IPA rings from PH rats compared with control rings. In contrast, ketamine produced a greater relaxation response in rings from 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 inhibitor, nitro-L-arginine (10(-4) M), inhibited the relaxation in response to acetylcholine in both control and PH rats. Pretreatment with ketamine (10(-4) M) had no effect on the relaxation response to any concentration of acetylcholine or SNP in either control or PH rats. We conclude that nitric-oxide-mediated relaxation, but not ketamine-induced relaxation, was impaired in structurally remodeled hypertensive pulmonary arteries. Ketamine had no effects on nitric oxide-mediated relaxation in either normal or PH rats.
Maruyama
K
K
Department of Anesthesiology, Mie University School of Medicine, Japan.
Maruyama
J
J
Yokochi
A
A
Muneyuki
M
M
Miyasaka
K
K
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D015237:Dinoprost / Q000494:pharmacology; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000503:physiopathology*; D000860:Hypoxia / Q000150:complications*; D066298:In Vitro Techniques; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000494:pharmacology; D019335:Nitroarginine; D009599:Nitroprusside / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects* / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects*
D009599:Nitroprusside; D019335:Nitroarginine; D009569:Nitric Oxide; D007649:Ketamine; D001120:Arginine; D015237:Dinoprost; D000109:Acetylcholine