Background: The smooth muscles of blood vessels express relaxant β-adrenoceptor, which functions as a negative feed-back system against α1-adrenoceptor-mediated contraction. Although β-adrenoceptor-mediated vascular smooth relaxation is generally thought to be triggered through a cyclic adenosine monophosphate (cAMP)-dependent pathway, a recent report has suggested a principal role for the nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) pathway. Thus, in this study, we examined whether the NO-cGMP pathway played an essential role in β-adrenoceptor-mediated smooth muscle direct relaxation in the rat thoracic aorta. Methods: The effects of an NO synthase inhibitor (L-NNA) or a soluble guanylyl cyclase inhibitor (ODQ) on the relaxation responses to β-adrenoceptor agonists were examined in endothelium-denuded rat thoracic aortas. The effects of β-adrenoceptor agonists on arterial cGMP content were also examined. Results: Both L-NNA and ODQ potently suppressed acetylcholine (ACh)-induced, endothelium-dependent relaxation. ODQ also largely suppressed endothelium-independent relaxation induced by an NO donor ((±)-(E)-4-ethyl-2-(E)-hydroxyimino-5-nitro-3-hexenamide NOR3). However, relaxation of the endothelium-denuded aortas in response to the β-adrenoceptor agonists isoprenaline, salbutamol, isoprenaline or CGP-12177A in the presence of propranolol, or noradrenaline was not substantially reduced by L-NNA or ODQ. Neither isoprenaline nor noradrenaline affected arterial cGMP content, whereas NOR3 caused an approximately 30-fold increase in cGMP content. Conclusions: Our findings suggested that the NO-cGMP pathway had an insignificant effect on endothelium-independent smooth muscle direct relaxation in the rat thoracic aorta in response to β-adrenoceptor agonists of any subtype (β1, β2, or β3).
Shunsuke et al. (Thu,) studied this question.
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