title: Pharmacodynamic characterization of nitric oxide-mediated vasodilatory activity in isolated perfused rat mesenteric artery bed.
abstract: Vasodilation profiles following a short-term infusion of nitric oxide (NO), acetylcholine (ACh), and sodium nitroprusside (SNP) into an isolated perfused mesenteric artery bed were analyzed in rats to examine their vasodilatory efficacy under physiological conditions. These compounds commonly increase the intracellular NO concentration to exert vasodilatory activity. In an experiment with exogenous NO infusion where 100 µl of 1 : 300 diluted NO-saturated solution (approx. 53 pmol of NO) was applied, the infusion caused transient vasodilation in a dose-dependent manner, with the peak vasodilation value being 74.7% of the maximum relaxation value. In experiments with ACh, the peak vasodilation value was 81.5% of the maximum at a dose of 60 pmol. The vasodilation profile of ACh was similar to that of NO infusion, but the ACh-induced vasodilation reduced at a slower rate than that induced by NO infusion. The vasodilatory activity of SNP was less potent than that of ACh, and its peak value was 62.8% of the maximum at a dose of 2000 pmol. However, SNP activity was augmented by removing the vascular endothelia of the mesenteric artery bed, and the peak value reached 67.3% of the maximum at a dose of 60 pmol. Pharmacodynamic analysis indicated that NO and ACh are equivalent regarding their vasodilatory efficacy, while the efficacy of SNP was less than 1% of theirs, as the arterial vascular endothelium impeded intracellular SNP-related NO generation, by which 95% of SNP's vasodilatory efficacy was negated. These findings will be helpful to understand factors influencing the therapeutic efficacy of vasodilators.
authors: Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Japan.
authors: Shinsuke
authors: S
authors: Inoue
authors: Tetsuya
authors: T
authors: Aiba
authors: Yasuyuki
authors: Y
authors: Masaoka
authors: Keiko
authors: K
authors: Shimizu
authors: Yukiko
authors: Y
authors: Komori
authors: Mitsunobu
authors: M
authors: Mio
authors: Shingo
authors: S
authors: Takatori
authors: Hiromu
authors: H
authors: Kawasaki
authors: Yuji
authors: Y
authors: Kurosaki
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology; D009569:Nitric Oxide / Q000494:pharmacology* / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000502:physiology*
chemical_list: D009599:Nitroprusside; D009569:Nitric Oxide; D000109:Acetylcholine