title: Contractile responses of aortae from WKY and SHR to vasoconstrictors.
abstract: Aortae taken from spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats aged 4, 8 and 16 weeks were prepared as rings and used to measure the effects of five vasoconstrictors. The endothelium was removed in order to measure selectively the contractile responses induced by potassium chloride (KCl), phenylephrine (PHE), angiotensin-II (Ang II), endothelin-1 (ET-1) and human urotensin-II (U-II). These responses were assumed to derive from the activation of specific receptors (namely alpha1, AT1, ETA and UT-II) or from depolarization of the smooth muscle fibers by KCl. Specific antagonists prazosin, losartan, BQ-123 and [Orn8]-UII were used at various concentrations for a pharmacological characterization of these latter receptor systems. The primary purpose of the study was to explore mechanisms or factors that may intervene in the development and maintenance of high blood pressure in SHR. Results indicate that isolated aortae of SHR and WKY contain contractile sites (receptors) whose pharmacological profiles (pEC50 for agonists, pA2 for antagonists) are very similar to those of other biological systems and should be considered as typical for the alpha1, AT1, ETA and UT-II receptor types. Aortae taken from SHR 4 (non hypertensive), 8 and 16 weeks old (hypertensive) responded to the vasoconstrictors with reduced maximal contractions compared to those of age-matched WKY. These unexpected reduced responses of aortae, observed with the five vasoconstrictors, may be attributed to a non specific lesions. Maximal contraction of aortae from SHR increased from 4 to 16 weeks for KCI, PHE and U-II, decreased for Ang II, and remained stable for ET-1. There was also an age-dependent increase of maximal contraction induced by U-II in WKY. It is suggested that aortae from SHR undergo early remodelling that leads to reduced contractility in vitro and possibly to vessel rigidity in vivo. The factors involved in this process appear to be of genetic origin since they are present before hypertension: they may contribute to modify aortic compliance and perhaps vascular resistance in hypertensive animals and thus being the cause and not the consequence of high blood pressure.
authors.affiliation: Department of Pharmacology, University of Sherbrooke, Sherbrooke, Quebec, Canada.
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Gendron
authors.forename: Fernand
authors.initials: F
authors.lastname: Gobeil
authors.forename: Josée
authors.initials: J
authors.lastname: Morin
authors.forename: Pedro
authors.initials: P
authors.lastname: D'Orléans-Juste
authors.forename: Domenico
authors.initials: D
authors.lastname: Regoli
mesh_terms: D000367:Age Factors; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology; D001794:Blood Pressure; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology; D006339:Heart Rate; D006973:Hypertension / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014579:Urotensins / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D019332:Endothelin-1; D014579:Urotensins; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D010656:Phenylephrine; D011189:Potassium Chloride; C029677:urotensin II