6533b81ffe1ef96bd1278532

RESEARCH PRODUCT

Changes in Adrenoceptors and G-Protein-Coupled Receptor Kinase 2 in <smlcap>L</smlcap>-NAME-Induced Hypertension Compared to Spontaneous Hypertension in Rats

subject

description

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 <smlcap>L</smlcap>-NAME (N<sup>G</sup>-nitro-<smlcap>L</smlcap>-arginine methyl-ester) (<smlcap>L</smlcap>-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 α<sub>1</sub>-AR-mediated contraction, and an impairment of endothelium-dependent vasorelaxation, with both changes occurring independently of the hypertensive model; (2) a diminished sensitivity to α<sub>1</sub>-AR-induced vasoconstriction along with increased β<sub>2</sub>-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 β<sub>1</sub>-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 β<sub>2</sub>-AR function in conductance vessels but not β<sub>1</sub>-AR function in resistance vessels.