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

• Published in: Life sciences (1973) 2019-05, Vol.225, p.29-38
• Main Authors: Teixeira-da-Silva, José Jairo, Nunes-Moreira, Hicla Stefany, Silva, Cristina Oliveira, Lahlou, Saad, Naro, Fabio, Xavier, Fabiano Elias, Duarte, Glória Pinto
• Format: Article
• Language: English
• Subjects: Acetylcholine; Anions; Aorta; Bioavailability; Blood pressure; Caveolin; Contraction; Cyclooxygenase-1; Cyclooxygenase-2; Endothelial dysfunction; Hypertension; Inflammation; Nitric oxide; Oxidative stress; Phenylephrine; Phosphodiesterase; Proteins; Rodents; Sildenafil; Single-nucleotide polymorphism; Sodium; Sodium nitroprusside; Superoxide; Superoxide anions; Vasoconstriction; Vasodilation; Vasorelaxation
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2019.03.074

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. 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. 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. 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.