| Background and Objective Hypertension is the most common chronic disease and important risk factor of cardiovascular and cerebrovascular diseases. Epidemiological survey in China showed that risk factors of cardio-cerebral vascular diseases in order of priority are hypertention, smoking, hyperlipidemia, overweight or obesity, diabetes. The cardiovascular disease deaths are3.5million each year in our country, at least half is associated with hypertension. Due to its high death and disability rates, hypertention serious threats to human health and increase the social and economic burden, control of blood pressure can be significantly reduced cardiovascular events and stroke, then improve prognosis. Recently, research has found that hypertention in addition to leading to stroke, coronary heart disease, chronic kidney disease, and other complications, hypertension itself and antihypertensive medications may lead to sexual dysfunction. Young and middle-aged hypertension prevalence in China is on the rise in recent years, patients receiving antihypertensive treatment often complain of erectile dysfunction (ED), making it one of the main reasons for loss compliance of antihypertensive treatment and reduction blood pressure control rate, many patients are eager to lower blood pressure while the quality of sex life are unaffected or improved. Renin-angiotensin system (RAS) blockers in extensive clinical application, studies confirmed that the male reproductive system exist the components of RAS such as angiotensin, angiotensin converting enzyme and its receptor. Therefore, RAS blockers might change the local RAS component concentrations in male reproductive system and then affect the physiological function of leydig cells. The current study will explore the relationship between hypertention, erectile function and sex hormones, discusses the effects and the possible mechanism that hypertention and RAS blockers on erectile function in spontaneously hypertensive rats (SHRs) by observing the effects of RAS blockers valsartan and benazepril on erectile function, testicles weight, gonad index (GSI) and serum sex hormones (testosterone, estradiol, progesterone) levels, then provides the basis for the reasonable choice of antihypertensives in clinical.Methods24Specific pathogen Free(SPF) SHRs were distributed randomly in three groups:Valsartan group(received valsartan30mg/(kg·day) dissolved in0.5ml distilled water, Group A, n=8); Benazapril group (received benazapril10mg/(kg·day) dissolved in0.5ml distilled water, Group B, n=8)and SHR-control group (received distilled water0.5ml/day, Group C, n=8). Then8SPF Wistar-Kyoto rats(WKYs) with the same age were the control group(Group D) and received distilled water0.5ml/day. Drug concentrations were adjusted bi-weekly to account for fluctuations in body weight. The rats were maintained in individual cages with a12-hour light-dark cycle and a room temperature of24to28℃. They were provided with free access to standard rat chow and tap water, and acclimated to the room for1week before the experiments.Body weight, systolic blood pressure (SBP) were measured and blood samples for testosterone, estradiol, pregnendione analysis were took from vena ophthalmica serum at baseline. After treatment as described above for2months, body weight and SBP were measured again and then the intracavernous pressure (ICP) and mean arterial pressure(MAP) were measured by type RM6240B/C multi-channel physiological signal acquisition and processing system with0,2,5Vof cavernous nerve electrostimulation. The influence of hypertention and antihypertensive agents on erectile function was evaluated by ICP/MAP. All the rats were sacrificed by carotid artery bloodletting, the testicles were removed for measuring testicular weight and GSI [(Gonad weight/total body weight)×100] quickly and serum was stored to measure serum testosterone, estradiol, pregnendione level by electrochemilumin-escence assay.Results After intervention for2months, both valsartan and benazapril reduced the SBP(P<0.01) but the SBP increased in rats weren’t offered antihypertensive agents(P<0.01). The ICP/MAP of group C was lower than the other three groups at0,2,5V of cavernous nerve electrostimulation(P<0.01) and there was a significant negative correlation between SBP and ICP/MAP(P<0.01). The ICP/MAP of group D was higher than group A and B (P<0.01), the group B (P<0.05) and there was no significant difference in the three groups (P>0.05) at0,2,5V of electrostimulation, respectively. No significant difference of testicle weight and GSI were found in all the groups(P>0.05), single factor linear correlation analysis showed no correlation between SBP and GSI as well. As compared with group A,B and D, the serum testosterone level was lower in group C, it was lower than baseline as well(P<0.05). However, the estradiol in group C was higher than group B and D(P <0.05). In addition, pregnendione in group C was lower than the other three groups but only a significant difference was found as compared with group D (P<0.05). Single factor linear correlation analysis showed that there was a significant positive correlation between SBP and estradiol (r=0.463,P<0.01) while a negative correlation between SBP and testosterone(r=-0.398,P<0.05), and pregnendione(r=-0.454, P<0.05) as well. Serum estrogen/testosterone ratio and erectile function with0,2,5v electrostimulation cavernous nerve showed a significant negative correlation (r=-0.547, P<0.01; r=-0.552, P<0.01; r=-0.596, P<0.01), pregnendione and erectile function with the corresponding strength of electrostimulation showed a significant positive correlation (r=0.448, P<0.05; r=0.433, P<0.05; r=0.537, P<0.01).Conclusions Hypertention have a negative impact on erectile function in SHRs, the SBP and erectile function was significantly negatively correlated, which may be associated with hypertention leading to serum testosterone reduced and estradiol levels increased, resulting in the imbalance of the ratio of estradiol and testosterone. RAS inhibitor valsartan and benazepril had no prejudice to erectile function and no significant effect on GSI in SHRs, valsartan may improved the erectile function to a certain extent, which may be due to valsartan and benazepril can maintain the ratio of serum sex hormone balance in SHRs, but the specific molecular mechanism still need further study. |
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