Different β-adrenoceptor subtypes coupling to cAMP or NO/ cGMP pathways: implications in the relaxant response of rat conductance and resistance vessels.

Background and Purpose To analyse the relative contribution of β₁-, β₂- and β₃-adrenoceptors ( Adrb) to vasodilatation in conductance and resistance vessels, assessing the role of cAMP and/or NO/ cGMP signalling pathways. Experimental Approach Rat mesenteric resistance artery ( MRA) and aorta were used to analyse the Adrb expression by real-time -PCR and immunohistochemistry, and for the pharmacological characterization of Adrb-mediated activity by wire myography and tissue nucleotide accumulation. Key Results The mRNAs and protein for all Adrb were identified in endothelium and/or smooth muscle cells ( SMCs) in both vessels. In MRA, Adrb1 signalled through cAMP, Adrb3 through both cAMP and cGMP, but Adrb2, did not activate nucleotide formation; isoprenaline relaxation was inhibited by propranolol (β₁, β₂), CGP20712A (β₁), and SQ22536 (adenylyl cyclase inhibitor), but not by ICI118,551 (β₂), SR59230A (β₃), ODQ (soluble guanylyl cyclase inhibitor), L- NAME or endothelium removal. In aorta, Adrb1 signalled through cAMP, while β₂- and β₃-subtypes through cGMP; isoprenaline relaxation was inhibited by propranolol, ICI118,551, ODQ, L- NAME, and to a lesser extent, by endothelium removal. CL316243 (β₃-agonist) relaxed aorta, but not MRA. Conclusion and Implication Despite all three Adrb subtypes being found in both vessels, Adrb1, located in SMCs and acting through the adenylyl cyclase/ cAMP pathway, are primarily responsible for vasodilatation in MRA. However, Adrb-mediated vasodilatation in aorta is driven by endothelial Adrb2 and Adrb3, but also by the Adrb2 present in SMCs, and is coupled to the NO/ cGMP pathway. These results could help to understand the different physiological roles played by Adrb signalling in regulating conductance and resistance vessels. [ABSTRACT FROM AUTHOR]