title: Endothelium-dependent contractions are associated with both augmented expression of prostaglandin H synthase-1 and hypersensitivity to prostaglandin H2 in the SHR aorta.
abstract: Prostaglandin H2 (PGH2 [endoperoxide]) is an immediate product of prostaglandin H (PGH) synthase activity (cyclooxygenase) and a likely candidate to mediate endothelium-dependent contractions evoked by acetylcholine in the aorta of the spontaneously hypertensive rat (SHR). Experiments were designed to investigate whether or not endothelium-dependent contractions were associated with an increased expression of PGH synthase, an augmented acetylcholine-induced release of PGH2, and/or a hypersensitivity of the smooth muscle to endoperoxides in SHR aorta compared with normotensive Wistar-Kyoto (WKY) aorta. In SHR aorta, endothelium-dependent contractions to acetylcholine were abolished by tenidap (10(-8) mol/L), a preferential PGH synthase-1 inhibitor, but slightly impaired by NS-398 (10(-6) mol/L), a preferential PGH synthase-2 inhibitor. PGH synthase-1 expression, which was evaluated by both reverse transcriptase-polymerase chain reaction and Western blotting, was about twofold greater in preparations with endothelium from SHR than from WKY rats. There was no difference in PGH synthase-1 expression between preparations with and those without endothelium in both strains. In SHR but not WKY aortas, acetylcholine (10(-5) mol/L, 5 minutes) caused a significant endothelium-dependent release of PGH2 as measured by gas chromatography/mass spectrometry. PGH2 evoked more potent contractions in rings without endothelium from SHR than from WKY rats, whereas the thromboxane analogue U46619 and prostaglandin F2 alpha caused a comparable response in both preparations. These results show that endothelium-dependent contractions to acetylcholine in SHR aorta are associated with a greater expression of PGH synthase-1, a significant release of PGH2, and a hypersensitivity of the smooth muscle to the endoperoxide.
authors.affiliation: Center for Experimental Therapeutics, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: T
authors.initials: T
authors.lastname: Ge
authors.forename: H
authors.initials: H
authors.lastname: Hughes
authors.forename: D C
authors.initials: DC
authors.lastname: Junquero
authors.forename: K K
authors.initials: KK
authors.lastname: Wu
authors.forename: P M
authors.initials: PM
authors.lastname: Vanhoutte
authors.forename: C M
authors.initials: CM
authors.lastname: Boulanger
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D001345:Autoradiography; D015153:Blotting, Western; D004730:Endothelium, Vascular / Q000502:physiology*; D005784:Gene Amplification; D006967:Hypersensitivity; D008297:Male; D009119:Muscle Contraction; D009131:Muscle, Smooth, Vascular / Q000276:immunology / Q000502:physiology; D016133:Polymerase Chain Reaction; D044262:Prostaglandin H2; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis / Q000235:genetics*; D011463:Prostaglandins H / Q000032:analysis / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014158:Transcription, Genetic
chemical_list: D011463:Prostaglandins H; D012333:RNA, Messenger; D044262:Prostaglandin H2; D011451:Prostaglandin-Endoperoxide Synthases; D000109:Acetylcholine