title: Contractile responses and signal transduction of endothelin-1 in aorta and mesenteric vasculature of adult spontaneously hypertensive rats.
abstract: The contractile responses and generation of intracellular second messengers in response to endothelin-1 (ET-1), a potent vasoconstrictor peptide released locally by endothelial cells and involved in the regulation of vascular tone, were investigated in different segments of the vascular tree of adult 18-week-old spontaneously hypertensive rats (SHR) as compared with age-matched Wistar-Kyoto (WKY) rats. Aorta rings of SHR showed lower maximum response to ET-1 in comparison with WKY rats. Rings of the main superior mesenteric artery of SHR and WKY showed similar responses to ET-1. Small mesenteric resistance arteries of SHR, mounted on a wire myograph, developed similar tension to those of WKY rats in response to ET-1. The dose-response of inositol phosphates to ET-1 was significantly blunted in thoracic aorta of SHR compared with WKY rats, whereas it was similar in the mesenteric arterial bed. Baseline 1,2-diacylglycerol content was higher in thoracic aorta of SHR than WKY, while it was similar in the mesenteric arterial bed of the two strains. The response of 1,2-diacylglycerol to ET-1 was blunted in aorta of SHR, whereas no significant differences in diacylglycerol accumulation could be found in mesenteric vessels between SHR and WKY. In small mesenteric arteries, the dose-response to ET-1 of cytosolic free calcium, measured with the fluorescent dye Fura 2-AM, was similar in the two groups of rats. We conclude that in the aorta of 18-week-old SHR there is reduced generation of second messengers (inositol phosphates and diacylglycerol), which underlies its decreased response to ET-1. In mesenteric vessels (both proximal and distal) signal transduction is similar in SHR and WKY, and as a result contractile responses in both species are comparable. The responses to ET-1 of the arterial tree in terms of contractility and second messenger generation may reflect the adaptive processes taking place as a consequence of elevated blood pressure within the arterial wall of different segments of the vasculature of SHR.
authors.affiliation: Experimental Hypertension Laboratory, Université de Montréal, Canada.
authors.forename: P V
authors.initials: PV
authors.lastname: Nguyen
authors.forename: X P
authors.initials: XP
authors.lastname: Yang
authors.forename: G
authors.initials: G
authors.lastname: Li
authors.forename: L Y
authors.initials: LY
authors.lastname: Deng
authors.forename: J P
authors.initials: JP
authors.lastname: Flückiger
authors.forename: E L
authors.initials: EL
authors.lastname: Schiffrin
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D004075:Diglycerides / Q000096:biosynthesis / Q000378:metabolism; D016232:Endothelins / Q000097:blood / Q000494:pharmacology*; D006973:Hypertension / Q000503:physiopathology; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000096:biosynthesis / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D010716:Phosphatidylinositols / Q000096:biosynthesis / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D015290:Second Messenger Systems / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D014316:Tritium; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology
chemical_list: C011439:1,2-diacylglycerol; D004075:Diglycerides; D016232:Endothelins; D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D014316:Tritium; D002118:Calcium