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