Peroxynitrite hyperpolarizes smooth muscle and relaxes internal carotid artery in rabbit via ATP-sensitive K+ channels.
The goal of this study was to determine the effects of peroxynitrite (ONOO-) on smooth muscle membrane potential and vasomotor function in rabbit carotid arteries. ONOO- is known to affect vascular tone by several mechanisms, including effects on K+ channels. Xanthine (X, 0.1 mM), xanthine oxidase (XO, 0.01 U/ml), and a low concentration of sodium nitroprusside (SNP, 10 nM) were used to generate ONOO-. In the common carotid artery, X and XO (X/XO) in the presence of SNP tended to increase tension. In contrast, in the internal carotid artery, X/XO in the presence of SNP transiently hyperpolarized the membrane (-8.5 +/- 1.8 mV, mean +/- SE) and decreased tension (by 85 +/- 5.6%). In internal carotid arteries, in the absence of SNP, X/XO did not hyperpolarize the membrane and produced much less relaxation (by 23 +/- 5.6%) than X/XO and SNP. Ebselen (50 microM) inhibited both hyperpolarization and relaxation to X/XO and SNP, and uric acid (100 microM) inhibited relaxation. Glibenclamide (1 microM) abolished hyperpolarization and inhibited relaxation during X/XO and SNP. Charybdotoxin (100 nM) or tetraethylammonium (1 mM) did not affect hyperpolarization or relaxation, respectively. These results suggest that ONOO- hyperpolarizes and relaxes smooth muscle in rabbit internal carotid artery but not in common carotid artery through activation of K(ATP) channels.
Ohashi
Masuo
M
Cardiovascular Center and Dept. of Internal Medicine, Univ. of Iowa and Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242-1801, USA.
Faraci
Frank
F
Heistad
Donald
D
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001393:Azoles / Q000494:pharmacology; D002343:Carotid Artery, Internal / Q000187:drug effects*; D002374:Catalase / Q000494:pharmacology; D018999:Charybdotoxin / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D054833:Isoindoles; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009129:Muscle Tonus / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D016566:Organoselenium Compounds / Q000494:pharmacology; D030421:Peroxynitrous Acid / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects / Q000378:metabolism; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000494:pharmacology; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D014527:Uric Acid / Q000494:pharmacology
D000975:Antioxidants; D001393:Azoles; D007004:Hypoglycemic Agents; D054833:Isoindoles; D016566:Organoselenium Compounds; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D017382:Reactive Oxygen Species; D013757:Tetraethylammonium Compounds; C117780:mitochondrial K(ATP) channel; D018999:Charybdotoxin; D030421:Peroxynitrous Acid; D014527:Uric Acid; C042986:ebselen; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase; D005905:Glyburide