Functional and Morphological Improvement in Erectile Tissue of Hypertensive Rats by Long-Term Combined Therapy with Phosphodiesterase Type 5 Inhibitor and Losartan

Abstract

Erectile dysfunction (ED) is highly associated to cardiovascular disease, especially arterial hypertension. Phosphodiesterase type 5 (PDE5) inhibitors and angiotensin II receptor blockers (ARB) are both common and efficient therapy in patients with ED and arterial hypertension, respectively. To evaluate the effect of PDE5 inhibitor, sildenafil (S), and of ARB Losartan (L) in a continuous combined therapy for a long term on penile structures in a hypertensive rat model. During 6 months, four groups of male spontaneously hypertensive rats (SHR) and one of Wistar-Kyoto (WKY) rats, as control group, were studied: no-treatment SHR, SHR with L, SHR with S, SHR with S + L, and no-treatment WKY. Cavernous smooth muscle (CSM) and vascular smooth muscle (VSM) from cavernous arteries, collagen type III (COL-III), and endothelial nitric oxide synthase (eNOS) expression in cavernous space were evaluated. Functional and morphological differences between S and L in a continuous combined therapy vs. either drug as monotherapy on penile structures. After 6 months, SHR that received L, S, or combined therapy showed a similar reduction in blood pressure compared with untreated SHR. Nevertheless, SHR + L + S and control WKY showed significantly lower values of (i) CSM (P < 0.01), (ii) VSM (P < 0.01), and (iii) COL-III (P < 0.01) when compared with the untreated SHR and also with the SHR with monotherapy. Additionally, SHR + L + S, presented a higher eNOS expression in sinusoidal endothelium in comparison with the untreated SHR and the SHR with monotherapy (P < 0.01). In vitro studies revealed that SHR + L + S displayed a better relaxation response to acetylcholine than the untreated SHR and the SHR with monotherapy (P < 0.01). These results suggest that a long-term combined therapy using L and S is a useful tool for functional and structural modification in cavernous tissue from SHR.