Phenylephrine activates eNOS Ser(1177) phosphorylation and nitric oxide signaling in renal hypertensive rat aorta

Autor(es)

Silva, Bruno R. ^[1] ; Pernomian, Laena ^[2] ; Grando, Marcella D. ^[1] ; Bendhack, Lusiane M. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Pharmaceut Sci Ribeirao Preto, Pharmacol Lab, BR-14040903 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Pharmacol, BR-14040900 Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: European Journal of Pharmacology; v. 738, p. 192-199, SEP 5 2014.
• Citações Web of Science: 9

Resumo

The endothelial nitric oxide synthase (eNOS) plays an important role in the control of the vascular tone. This work aimed to evaluate the role of an alpha(1)-adrenoceptor agonist phenylephrine (PE) on eNOS activity and downstream signaling pathway activation in normotensive (2K) and renal hypertensive (2K-1C) intact-endothelium rat aortas. Concentration-effect curves were performed for PE in intact-endothelium aortas from 2K and 2K-1C rats, in the absence of or in the presence of NOS or soluble guanylyl cyclase (sGC) inhibitor Intact endothelium aortas were stimulated with PE in organ chambers and eNOS Ser(1177)/Thr(495) phosphorylation expression was evaluated by western blot. Nitric Oxide (NO) production was evaluated in isolated endothelial cells from 2K and 2K-1C rat aortas by flow-cytometry using NO selective fluorescent probe, DAE-2DA. The sGC activity/expression was also evaluated. PE-induced contractile response is lower in 2K-1C than in 2K intact-endothelium rat aorta. This is due to higher NOS Ser(1177) phosphorylation in 2K-1C, which induces the eNOS overactivation It was abolished by NOS or sGC inhibition. Phenylephrine reduces NO production in 2K as compared to the basal level, but it is not modified in 2K-1C. In PE-stimulated endothelial cells, the NO production is higher in 2K-1C than in 2K. Phenylephrine induces higher cGMP production in 2K-1C than in 2K, despite the lower expression of sGC in 2K-1C. Our results suggest that alphai-adrenoceptor activation contributes to the increased activity of the enzyme eNOS by Ser(1177) phosphorylation in 2K-1C intact endothelium aorta, which consequently decreases PP induced contractile response. (C) 2014 Elsevier B.V. All rights reserved. (AU)

• Processo FAPESP: 09/14219-9 - Mecanismos celulares envolvidos na disfunção endotelial e os efeitos do doador de Óxido Nítrico AuNPs-{Ru-4PySH}n em vasos de ratos hipertensos renais
• Beneficiário: Bruno Rodrigues Silva
• Modalidade de apoio: Bolsas no Brasil - Doutorado