title: Changes in adrenoceptors and G-protein-coupled receptor kinase 2 in L-NAME-induced hypertension compared to spontaneous hypertension in rats.
abstract: This work compares the expression of adrenoceptors (ARs) and G-protein-coupled receptor kinase (GRK) 2 (RT-PCR and immunoblotting) and functional responses in conductance (aorta) and resistance vessels (mesenteric resistance arteries; MRA) in two different models of rat hypertension: hypertension induced by chronic treatment with L-NAME (N(G)-nitro-L-arginine methyl-ester) (L-NAME-treated rats; LNHR), and genetically induced hypertension (spontaneously hypertensive rats; SHR). Changes found in the aorta, but not in the MRA, were: (1) a loss of contractile capacity, more evidently in α1-AR-mediated contraction, and an impairment of endothelium-dependent vasorelaxation, with both changes occurring independently of the hypertensive model; (2) a diminished sensitivity to α1-AR-induced vasoconstriction along with increased β2-AR-mediated vasodilation in LNHR, and (3) a lower expression of ARs and GRK2 in LNHR. The two latter changes are the opposite of those previously found in aortas of SHR. In the MRA of LNHR, a diminished sensitivity to isoprenaline, in parallel with a reduced expression of β1-AR, was observed without changes in GRK2 expression. In the MRA of SHR, the increased GRK2 expression was not accompanied by significant changes in either β-AR expression or the vasorelaxant potency of isoprenaline. The present results highlight that changes in AR function differ not only between vessels but also between hypertensive models. Moreover, they suggest that changes in GRK2 expression could contribute to regulating β2-AR function in conductance vessels but not β1-AR function in resistance vessels.
authors.affiliation: Departamento de Farmacología, Facultad de Farmacia, Universitat de València, Valencia, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Oliver
authors.forename: Nicla
authors.initials: N
authors.lastname: Flacco
authors.forename: Cristina
authors.initials: C
authors.lastname: Arce
authors.forename: M Dolores
authors.initials: MD
authors.lastname: Ivorra
authors.forename: M Pilar
authors.initials: MP
authors.lastname: D'Ocon
authors.forename: M Antonia
authors.initials: MA
authors.lastname: Noguera
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects; D054769:G-Protein-Coupled Receptor Kinase 2 / Q000378:metabolism*; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D018343:Receptors, Adrenergic, beta-2 / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
chemical_list: D018340:Receptors, Adrenergic, alpha-1; D018343:Receptors, Adrenergic, beta-2; D054769:G-Protein-Coupled Receptor Kinase 2; D019331:NG-Nitroarginine Methyl Ester