Aims: Spontaneously hypertensive rats (SHR) exhibit impaired endothelial vasodilation and enhanced vasoconstriction. The phosphodiesterase 5 (PDE5) inhibitor sildenafil (Sild) potentiates the nitric oxide (NO)- mediated effects exerting antioxidative and anti-inflammatory actions. In the present study, we hypothesized that Sild could improve endothelial function in SHR. Materials and methods: Male rats were treated daily for 60 days by oral gavage with Sild (45 mg/kg) before the onset of the hypertensive state (pre-hypertensive protocol). The aortic relaxation to acetylcholine (ACh), sodium nitroprusside (SNP) and the phenylephrine (Phe)-induced contraction was evaluated in SHR. Protein expression of eNOS, p-eNOS, caveolin, COX-1, COX-2, ERK and p-ERK was measured by Western blot. Key findings: Resting blood pressure was not modified by Sild administration. Treatment with Sild did not alter the relaxation response to SNP but improved the ACh-induced relaxation and reduced Phe-induced contraction in aortic rings from SHR. This protective effect of Sild could be attributed to reduced superoxide anions (O2 −) generation, cyclooxygenase type 2 (COX-2) protein downregulation and increased NO bioavailability. Significance: Sild improves endothelial function in SHR aorta without affecting resting blood pressure values. These results indicate that PDE5 inhibition has a potential role in the improvement of vascular function and could be an adjuvant in the treatment of essential hypertension.

Chronic administration of sildenafil improves endothelial function in spontaneously hypertensive rats by decreasing COX-2 expression and oxidative stress / Teixeira-da-Silva, José Jairo; Nunes-Moreira, Hicla Stefany; Silva, Cristina Oliveira; Lahlou, Saad; Naro, Fabio; Xavier, Fabiano Elias; Duarte, Glória Pinto. - In: LIFE SCIENCES. - ISSN 0024-3205. - 225:(2019), pp. 29-38. [10.1016/j.lfs.2019.03.074]

Chronic administration of sildenafil improves endothelial function in spontaneously hypertensive rats by decreasing COX-2 expression and oxidative stress

Teixeira-da-Silva, José Jairo;Naro, Fabio;
2019

Abstract

Aims: Spontaneously hypertensive rats (SHR) exhibit impaired endothelial vasodilation and enhanced vasoconstriction. The phosphodiesterase 5 (PDE5) inhibitor sildenafil (Sild) potentiates the nitric oxide (NO)- mediated effects exerting antioxidative and anti-inflammatory actions. In the present study, we hypothesized that Sild could improve endothelial function in SHR. Materials and methods: Male rats were treated daily for 60 days by oral gavage with Sild (45 mg/kg) before the onset of the hypertensive state (pre-hypertensive protocol). The aortic relaxation to acetylcholine (ACh), sodium nitroprusside (SNP) and the phenylephrine (Phe)-induced contraction was evaluated in SHR. Protein expression of eNOS, p-eNOS, caveolin, COX-1, COX-2, ERK and p-ERK was measured by Western blot. Key findings: Resting blood pressure was not modified by Sild administration. Treatment with Sild did not alter the relaxation response to SNP but improved the ACh-induced relaxation and reduced Phe-induced contraction in aortic rings from SHR. This protective effect of Sild could be attributed to reduced superoxide anions (O2 −) generation, cyclooxygenase type 2 (COX-2) protein downregulation and increased NO bioavailability. Significance: Sild improves endothelial function in SHR aorta without affecting resting blood pressure values. These results indicate that PDE5 inhibition has a potential role in the improvement of vascular function and could be an adjuvant in the treatment of essential hypertension.
2019
endothelial dysfunction; hypertension; phosphodiesterase; sildenafil; vasorelaxation
01 Pubblicazione su rivista::01a Articolo in rivista
Chronic administration of sildenafil improves endothelial function in spontaneously hypertensive rats by decreasing COX-2 expression and oxidative stress / Teixeira-da-Silva, José Jairo; Nunes-Moreira, Hicla Stefany; Silva, Cristina Oliveira; Lahlou, Saad; Naro, Fabio; Xavier, Fabiano Elias; Duarte, Glória Pinto. - In: LIFE SCIENCES. - ISSN 0024-3205. - 225:(2019), pp. 29-38. [10.1016/j.lfs.2019.03.074]
File allegati a questo prodotto
File Dimensione Formato  
Teixeira-da-Silva_Chronic_2019.pdf

solo gestori archivio

Tipologia: Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza: Tutti i diritti riservati (All rights reserved)
Dimensione 1.47 MB
Formato Adobe PDF
1.47 MB Adobe PDF   Contatta l'autore

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1270461
Citazioni
  • ???jsp.display-item.citation.pmc??? 2
  • Scopus 10
  • ???jsp.display-item.citation.isi??? 10
social impact