Biomedical subjects

Frank Faraci

Publications and source records attributed to Frank Faraci.

2 recordsLinked to original sources

PubMed2005

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.

Animals↗

PubMed2003

Enhanced vasoconstrictor responses in eNOS deficient mice.

Previous studies suggest that vasoconstriction is modulated by nitric oxide (NO). Contractions to ET-1 and/or thromboxane may be enhanced during chronic deficiency in expression or activity of NO synthase (NOS). Multiple isoforms of NOS are expressed within the vessel wall and purely pharmacological approaches cannot define the role of each. We tested the hypothesis that vasoconstriction to endothelin-1 (ET-1) and/or the thromboxane mimetic, U46619, is enhanced under conditions of chronic, selective deficiency in endothelial NOS (eNOS-/-) by examining responses in aorta from eNOS-/- mice compared to wild type (eNOS+/+). ET-1 produced dose-dependent contraction of aorta from eNOS+/+ mice that was increased twofold following acute inhibition of all NOS isoforms with N(G)-nitro-L-arginine (L-NNA). In eNOS-/- mice, contractions to ET-1 were increased twofold compared to eNOS+/+. L-NNA had no effect. Although contraction of the aorta to thromboxane mimetic U46619 was increased at lower concentrations, maximal contractions to U46619 were not increased following acute inhibition of NOS or in eNOS-/- mice. These studies provide direct evidence that vasoconstriction to ET-1 and thromboxane is augmented in the face of eNOS deficiency, demonstrating that eNOS normally inhibits vascular contractile responses.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗