Effect of an angiotensin II receptor blocker and a calcium channel blocker on hypertension associated penile dysfunction in a rat model

Abstract

Possible effect of olmesartan, an angiotensin II receptor blocker (ARB), or nifedipine, an L-type calcium channel blocker, on penile dysfunction in the spontaneously hypertensive rat (SHR) was investigated in this study. Twelve-week-old male SHRs were treated with olmesartan (1 or 3 mg/ kg, per orally (p.o.)) or nifedipine (30 mg/kg, p.o.) once a day for 6 weeks. Wistar rats and SHRs with vehicle treatment were used as controls. Penile cGMP and malondialdehyde concentrations, and mRNA levels of endothelial and neuronal NO synthase (eNOS and nNOS) were measured. Penile function was evaluated by organ bath studies with norepinephrine-induced contractions and acetylcholine-induced relaxations. The SHR showed significantly increased blood pressure, decreased cGMP concentrations, increased malondialdehyde concentrations, decreased eNOS and nNOS mRNA levels, norepinephrine-induced hyper-contractions, and acetylcholine-induced hyporelaxations in the penile tissue compared to the Wistar rat. Both nifedipine and olmesartan significantly decreased blood pressure, increased cGMP and normalized the hyper-contractions and hypo-relaxations observed in the SHR group. However, not nifedipine but olmesartan improved the malondialdehyde concentrations and increased mRNA levels of eNOS and nNOS in the penis. Our results indicate that the hypertension-associated penile dysfunction might be treated with ARBs such as olmesartan better than calcium channel blockers, such as nifedipine.Hypertension induces vascular remodeling, pathological changes in the penis, and subsequent diminished blood supply to the penile tissue. In addition, hypertension represents one of the major risk factors for the development of vasculogenic erectile dysfunction (ED) (16,28). ED frequently appears in hypertensive patients than in normotensive individuals (10). The extent of ED directly depends on the degree and time of hypertension (8). Clinical studies show that approximately 30% of hypertension patients have ED compared to 9.6% in the common population (12, 28). Thus, antihypertensive therapies in hypertension-related ED patients are necessary in order to reduce the blood pressure and further protect the cavernous tissue. However, some of these therapies did not always improve the symptoms of ED in hypertensive patients (22,23). In clinical studies, the older antihypertensive drugs, i.e., diuretics and β-adrenoreceptor blockers, may exert detrimental effect on ED. On the other hand, more recent drugs have neutral (calcium channel blockers and angiotensin-converting enzyme (ACE) inhibitors) or favorable (angiotensin II type 1 receptor (AT1R) blockers (ARBs)) effects (11,22). These data suggest that blood pressure control may not be the only treatment strategy to improve erec-

A Review on Erectile Dysfunction Among Hypertensive Patients on Pharmacotherapy

“…In a robust study by Della and colleagues, valsartan use was associated with an improved sexual function among 2202 hypertensive individuals recruited. In several pre-clinical trials, intracavernous injection of angiotensin-II led to reduced intracavernosal pressure and prevented erection as well as aborted erection already in place [74].…”

The Different Therapeutic Choices with ARBs. Which One to Give? When? Why?

“…Several preclinical and clinical studies have shown beneficial effects of some ARBs on sexual function; however, not all studies have shown significant results compared with placebo [ 97 , 98 ]. In mice, irbesartan was shown to improve penile endothelial function by reduction of vascular and cavernosal oxidative stress, while olmesartan improved the malondialdehyde concentrations and increased messenger ribonucleic acid (mRNA) levels of endothelial nitric oxide synthase (eNOS) and neuronal nitric oxide synthase (nNOS) in the penis [ 99 , 100 ].…”