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This Article Full Text Full Text (PDF) All Versions of this Article: 297/1/H134    most recent 00023.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Figueroa, X. F. Articles by Huidobro-Toro, J. P. PubMed PubMed Citation Articles by Figueroa, X. F. Articles by Huidobro-Toro, J. P.

NO production and eNOS phosphorylation induced by epinephrine through the activation of β-adrenoceptors

Centro de Regulación Celular y Patología, Instituto Milenio de Biología Fundamental y Aplicada, Unidad de Regulación Neurohumoral, Departamento de Ciencias Fisiológicas, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Casilla, Santiago, Chile

Submitted 12 January 2009 ; accepted in final form 4 May 2009

Epinephrine plays a key role in the control of vasomotor tone; however, the participation of the NO/cGMP pathway in response to β-adrenoceptor activation remains controversial. To evaluate the involvement of the endothelium in the vascular response to epinephrine, we assessed NO production, endothelial NO synthase phosphorylation, and tissue accumulation of cGMP in the perfused arterial mesenteric bed of rat. Epinephrine elicited a concentration-dependent increase in NO (EC₅₀ of 45.7 pM), which was coupled to cGMP tissue accumulation. Both NO and cGMP production were blocked by either endothelium removal (saponin) or NO synthase inhibition (N-nitro-L-arginine). Blockade of β₁- and β₂-adrenoceptors with 1 µM propranolol or β₃-adrenoceptor with 10 nM SR 59230A displaced rightward the concentration-NO production curve evoked by epinephrine. Selective stimulation of β₁-, β₂-, or β₃-adrenoceptors also resulted in NO and cGMP production. Propranolol (1 µM) inhibited the rise in NO induced by isoproterenol or the β₂-adrenoceptor agonists salbutamol, terbutaline, or fenoterol. Likewise, 10 nM SR 59230A reduced the effects of the β₃-adrenoceptor agonists BRL 37344, CGP 12177, SR 595611A, or pindolol. The NO production induced by epinephrine and BRL 37344 was associated with the activation of the phosphatidylinositol 3-kinase/Akt pathway and phosphorylation of eNOS in serine 1177. In addition, in anaesthetized rats, bolus administration of isoproterenol, salbutamol, or BRL 37344 produced NO-dependent reductions in systolic blood pressure. These findings indicate that β₁-, β₂-, and β₃-adrenoceptors are coupled to the NO/cGMP pathway, highlighting the role of the endothelium in the vasomotor action elicited by epinephrine and related β-adrenoceptor agonists.

endothelial nitric oxide synthase; endothelial cells; vasodilation