title: Endothelium-Dependent and -Independent Vasodilator Effects of Dimethyl Sulfoxide in Rat Aorta.
abstract: This study examined the mechanism of vasorelaxation induced by dimethyl sulfoxide (DMSO) in endothelium-intact and -denuded rat aorta. DMSO (0.1-3%) inhibited phenylephrine (PE, 1 μmol/l)-induced contraction in a dose-dependent manner. However, this relaxation was lower in the absence of the endothelium. Increase in DMSO-induced relaxation in the presence of the endothelium was attenuated by preincubation in L-NG-nitroarginine methyl ester (L-NAME, 100 μmol/l) and by the removal of the endothelium. In the aorta with endothelium, DMSO (3%) and CCh (3 μmol/l) increased cGMP contents, significantly and L-NAME (100 μmol/l) inhibited the DMSO-induced increases of cGMP. In fura 2-loaded endothelium-denuded aorta, cumulative application of DMSO (1-3%) inhibited PE-induced muscle tension; however, this application did not affect the [Ca2+]i level. In PE-precontracted endothelium-denuded aorta, relaxation responses to fasudil were significantly less in the presence of DMSO compared to the control. These results suggest that DMSO causes relaxation by increasing the cGMP content in correlation with the release of NO from endothelial cells and by decreasing the Ca2+ sensitivity of contractile elements partly via inhibiting Rho-kinase in rat aorta.
authors.affiliation: Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Nippon Veterinary and Life Science University, Musashino, Tokyo, Japan.
authors.forename: Takeharu
authors.initials: T
authors.lastname: Kaneda
authors.forename: Noriyasu
authors.initials: N
authors.lastname: Sasaki
authors.forename: Norimoto
authors.initials: N
authors.lastname: Urakawa
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Shimizu
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D002118:Calcium / Q000502:physiology; D006152:Cyclic GMP / Q000378:metabolism; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000502:physiology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D014665:Vasodilator Agents; D010656:Phenylephrine; D006152:Cyclic GMP; D002118:Calcium; D004121:Dimethyl Sulfoxide