title: Beta-adrenoceptor-mediated vascular relaxation in spontaneously hypertensive rats.
abstract: Although the impairment of beta-adrenoceptor (beta-AR)-induced vascular relaxation to isoprenaline has been extensively described, discrepancy persisted in the literature. In this work, we investigated beta-AR-induced relaxation in spontaneously hypertensive and normotensive rats aorta. We attempted to determine beta-AR subtypes involved in order to understand the conflicting data regarding the beta-AR-induced vasodilation to isoprenaline. Aortic rings isolated from 12-week-old Wistar Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs) were placed in organ baths and constricted with phenylephrine (alpha1-AR agonist). Then, cumulative concentration-relaxation curves (CCRC) to AR agonists were constructed. In intact aortic rings from both strains, isoprenaline (a nonselective beta-AR agonist) (0.001-10 microM) induced similar concentration-dependent relaxations. CCRC was shifted to the right and upward in the presence of nadolol (a nonspecific beta1 and beta2-AR antagonist) (10 microM). After endothelium removal, the response to isoprenaline was partly inhibited in WKY rats, but was strongly inhibited in SHRs. In WKY rats, isoprenaline-induced endothelium-independent relaxation was not modified in the presence of nadolol but was inhibited in the presence of CGP 20712A (low-affinity-state beta1-AR antagonist). In endothelium-denuded rings, SR 58611A (a preferential beta3-AR agonist) (0.1-30 microM) produced a very small relaxation in both strains. In WKY rats, CGP 12177 (CGP) (0.1-30 microM) and cyanopindolol (0.01-3 microM) (partial beta3-AR and low-affinity-state beta1-AR agonists with beta1-AR and beta2-AR antagonistic properties) produced endothelium-independent relaxations. CGP-induced effect was significantly inhibited by CGP 20712A (10 microM) or bupranolol (10 microM) (low-affinity-state beta1-AR antagonists). In SHRs, similarly to the impaired endothelium-independent relaxation to isoprenaline, endothelium-independent relaxations to CGP and cyanopindolol were greatly blunted. These relaxations were not modified in the presence of CGP 20712A. In endothelium-denuded rings pretreated with pertussis toxin, CGP-induced relaxation was not modified in WKY rats, but was partly restored in SHRs. In conclusion, these results showed, that in 12-week-old SHRs, the endothelium-independent component of the relaxation to isoprenaline was impaired, and this impairment could involve the low-affinity-state beta1-AR. G(i) protein overexpression and/or overstimulation may be possible factors that contribute to this alteration in hypertension.
authors.affiliation: Unité de Physiopathologie Animale et de Pharmacologie Fonctionnelle, UPSP 5304, Ecole Nationale Vétérinaire de Nantes, BP 40706, 44307 Nantes Cedex 03, France.
authors.forename: Yassine
authors.initials: Y
authors.lastname: Mallem
authors.forename: Delphine
authors.initials: D
authors.lastname: Holopherne
authors.forename: Olivier
authors.initials: O
authors.lastname: Reculeau
authors.forename: O
authors.initials: O
authors.lastname: Le Coz
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Desfontis
authors.forename: Marc
authors.initials: M
authors.lastname: Gogny
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology*; D010869:Pindolol / Q000031:analogs & derivatives* / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
chemical_list: D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D013764:Tetrahydronaphthalenes; C047975:cyanopindolol; D010869:Pindolol; D007545:Isoproterenol; C076252:amibegron; C033394:CGP 12177