Differences Between Candesartan and Hydralazine in the Protection of Penile Structures in Spontaneously Hypertensive Rats

Abstract

Introduction Previous studies indicate that angiotensin type I receptor antagonists present a beneficial effect on penile structures in hypertensive rats. However, at present there is no substantial information concerning the functional aspect of this class of antihypertensive drugs. Aim To determine, by in vitro studies, functional effects of Candesartan in comparison with a traditional vasodilating agent, Hydralazine, on penile structures in a rat model of arterial hypertension. Methods During 4 months, three groups of male spontaneously hypertensive rats (SHR) and one of Wistar–Kyoto (WKY) rats, as control group, were studied: SHR without treatment; SHR with Candesartan cilexetil 7.5 mg/kg/day; SHR with Hydralazine 50 mg/kg/day; and WKY rats without treatment. Cavernous smooth muscle strips were mounted in an organ bath system for in vitro studies. In addition, cavernous smooth muscle and vascular smooth muscle from cavernous arteries, cavernous tissue fibrosis, and collagen type III were also evaluated by immunohistochemistry. Results After 4 months, SHR with Candesartan and Hydralazine showed similar reduction in blood pressure compared with untreated SHR. However, in vitro studies revealed that SHR with Candesartan displayed a better relaxation response to acetylcholine than SHR and SHR with Hydralazine (P < 0.01). Immunostaining indicates that only SHR with Candesartan and control WKY rats showed significantly lower values of: (i) cavernous smooth muscle (P < 0.01); (ii) vascular smooth muscle (P < 0.01); and (iii) collagen type III (P < 0.01) when compared with untreated SHR or SHR with Hydralazine. Additionally, SHR with Candesartan presented a higher endothelial nitric oxide synthase expression in sinusoidal endothelium in comparison with SHR, and SHR with Hydralazine (P < 0.01). Conclusion Candesartan presented equivalent blood pressure control compared with Hydralazine. However, only Candesartan showed a significant better response to acetylcholine, in in vitro studies, with a protective role against structural changes in vessels as well as in cavernous spaces of the erectile tissue.

Local renin–angiotensin systems in the genitourinary tract

“…Moreover, AT1 activation mediates an increase in RhoA/ Rho-kinase activity and a decrease in eNOS protein expression, which can be readily reversed by the AT1 antagonist losartan (Jin 2009). This effect is specifically related to Ang II, which is supported by the finding that other antihypertensive agents did not improve erectile function (Toblli et al 2004a;Mazza et al 2006). Similar findings have been demonstrated in rat models of agerelated ED (in normotensive animals), with losartan improving eNOS protein expression and erectile function (Park et al 2005a), and in diabetic ED-with improvement following valsartan administration.…”

Drugs Designed to Improve Endothelial Function: Effects on Erectile Dysfunction

“…Histological studies demonstrated lower content of cavernosal and vascular smooth muscle as well as type III collagen in candesartan treated rats as compared to untreated controls and hydralazine treated rats [13]. A similar 6 month study comparing the calcium channel blocker amlodipine to the ARB losartan was revealing of similar antihypertensive efficacy between the drugs; however, losartan treated rats had diminished cavernosal and vascular smooth muscle as well as type III collagen, an effect that was not observed in the amlodipine treated rats.…”

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

“…The impairment of NOS and NO availability should lead to develop ED (30,36). Mazza et al reported that treatment with an ARB, candesartan, improved cavernous sinusoidal eNOS and acetylcholine-induced hypo-relaxation in the SHR (25). Angiotensin II is locally produced and secreted from penile endothelial cells and smooth muscle cells (18).…”

“…Also, hypertrophy of corpus cavernous smooth muscle and vascular smooth muscle has been confirmed in the SHR (32). In previous studies, the protective effect of ARB, such as losartan and candesartan, was already investigated in the penis in the SHR (9,25). Olmesartan medoxomil (olmesartan) is a newer ARB than losartan, and more effective to antagonize the AT1R (2).…”

“…The endothelium-mediated relaxation was measured as the concentration-response curve to acetylcholine (1 × 10 −8 to 3 × 10 −5 M) in strips precontracted with the submaximal dose of norepinephrine. In each strip, the concentrations of submaximal contraction were determined and were approximately from 1 × 10 (25). The renin-angiotensin system (RAS) has an important role in the ED regarding the remodelling process (27).…”