Managing erectile dysfunction in hypertension: the effects of a continuous training programme on biomarker of inflammation

Authors

  • Sikiru Lamina,

    1. Physiology Department, Faculty of Medical Sciences, Jimma University, Jimma, Ethiopia, Medical Rehabilitation Department, Faculty of Health Sciences And Technology, University of Nigeria, Enugu Campus, Enugu, and
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  • Chuba G. Okoye,

    1. Physiology Department, Faculty of Medical Sciences, Jimma University, Jimma, Ethiopia, Medical Rehabilitation Department, Faculty of Health Sciences And Technology, University of Nigeria, Enugu Campus, Enugu, and
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  • Theophilus T. Dagogo

    1. Department of Medicine, Murtala Muhammed Specialist Hospital, Kano, Nigeria
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Sikuru Lamina, Department of Physiology/Physiotherapy, Jimma University, Jimma, Box 378, Jimma, Ethiopia.
e-mail: siklam_86@yahoo.co.uk

Abstract

OBJECTIVE

To determine the effect of a continuous training programme on C-reactive protein (CRP) levels, and in the management of erectile dysfunction (ED) in older men with hypertension.

PATIENTS AND METHODS

In all, 22 men with hypertension and ED (mean age 61.8 years, sd 7.79) were involved in continuous training (35–59% of heart rate maximum reserve) for 8 weeks for 45–60 min, while 21 age-matched control hypertensives (mean age 64 years, sd 8.53) remained sedentary during this period. The International Index of Erectile Function (IIEF) questionnaire was used to assess the outcome of ED. The Mann–Whitney U-test and Spearman correlation were used to analyse the results of the changes in IIEF and CRP.

RESULTS

There was a significant effect of continuous exercise training on erectile function and CRP levels in hypertensive men with ED (P < 0.05).

CONCLUSIONS

A continuous training programme decreases CRP levels and is an effective means of noninvasive and nonpharmacological management of ED in men with hypertension.

Abbreviations
NO

nitric oxide

CRP

C-reactive protein

ED

erectile dysfunction

MMSH

Murtala Muhammed Specialist Hospital

IIEF

International Index of Erectile Function

(S)(D)BP

(systolic) (diastolic) blood pressure

HR

heart rate.

INTRODUCTION

The endothelium is vital to the maintenance of vascular health, and is a critical determinant of vascular tone and patency, reactivity, inflammation, vascular remodelling, and blood fluidity [1,2]. Nitric oxide (NO) is the most potent vasodilator and is secreted by the endothelium. It is synthesized from l-arginine by the endothelial enzyme NO synthase. NO released in response to sexual stimulation relaxes penile vascular smooth muscle by increasing the intracellular cGMP concentration. Vasodilatation of erectile tissues allows the sinusoidal spaces to fill with blood, resulting in the attainment and maintenance of an erection [3].

Increased serum levels of inflammatory mediators have been associated with numerous disease states, including atherosclerosis, type II diabetes, hypertension, depression and overall mortality [4]. C-reactive protein (CRP) levels are associated with the future development of hypertension, which suggests that hypertension is in part an inflammatory disorder [5]. Higher levels of CRP might increase blood pressure by reducing NO production in endothelial cells [6,7], resulting in vasoconstriction and increased production of endothelin 1 [8,9].

Several studies [10–12] have shown an inverse relationship between physical activity levels and biomarkers of inflammation in both healthy and hypertensive patients. Studies [13–17] also proposed the role of exercise in the management of erectile dysfunction (ED). However, no study has systematically and objectively determines the effect of exercise on the association between biomarkers of inflammation and ED. The purpose of the present study was therefore to determine the role and effect of exercise on the association of CRP and ED in older men with hypertension.

PATIENTS AND METHODS

The population for the study was 357 men with essential hypertension, attending the hypertension clinic of Murtala Muhammed Specialist Hospital (MMSH), Kano, Nigeria. Those complaining of ED were referred to a specialized clinic. The level of ED was established using the International Index of Erectile Function (IIEF) [18] and all men were questioned about previous ED treatment. Included in the study were men diagnosed with ED and who volunteered to participate in the study; aged 50–70 years, with chronic and stable (>1 year in duration) hypertension (systolic blood pressure, SBP, of 140–180 mmHg and a diastolic BP, DBP of 90–109 mmHg); and those who were previously on, or responded well to, methyldopa, for nonpsychological/psychiatric or depression disorders [19]. Excluded were men who were underweight or obese (body mass index <20 or >30 kg/m2), smokers, alcoholics, diabetics, those with other cardiac, renal or respiratory disease, BPH, liver failure, low testosterone level, or multiple sclerosis. Those involved in vigorous physical activities or had above average physical fitness (VO2max >27 and >33 mL/kg/min for ages >60 and >50 years, respectively) were also excluded.

In all, 43 hypertensive men with ED were assigned to two groups, treated by exercise, i.e. a continuous training programme (22), or a control sedentary group (21). The control group represented an age-matched randomized independent control before and after testing, to determine the influence of a continuous training programme on biomarkers of inflammation and on ED.

Ethical approval was granted by the Ethical Committee of Kano State Hospitals Management Board.

All men on antihypertensive drugs were asked to stop all forms of medication and were given placebo tablets (consisting mainly of lactose and inert substance) in a double-blind protocol [20]. All men, including those not on any antihypertensive medications, were placed on placebo tablets for 1 week, the ‘wash-out period’, to allow the effects of previous antihypertensive drugs/medications to subside. During the wash-out period all men were instructed to report to the hypertensive clinic for daily BP monitoring and general observation. The pre-test procedure was conducted on the last day of the wash-out period.

All tests and procedures were conducted in the Department of Physiotherapy, MMSH, between 08:00 and 10:00 h. Both before and after treatment venous blood samples were obtained after ≈12 h overnight fast (fasting blood sample), using a 5-mL syringe and the procedure described by Bachorik [21]. Serum samples were transferred to plastic containers, sealed, labelled and stored in a freezer at −80 °C until analysis [22].

CRP was assayed qualitatively and semiquantitatively using a commercial latex agglutination method (Dialab Producktion und Vertrieb Von Chemisch, GmBH, Vienna, Austria). For the qualitative assay, samples (50 mL, undiluted serum) and another for control (0.1 mL) were placed into separate circles on a disposable slide. The latex reagent was shaken gently and a drop added to both the serum and control, mixed and spread over the circles, the slide centrifuged at 80–100 rpm for 2 min, after which the presence or absence of macroscopically visible agglutination was recorded. The presence of agglutination indicated a CRP concentration of ≥6 mg/L.

For the semiquantitative assay, samples were serially diluted in 9 g/L saline, then the samples and an undiluted control (0.1 mL) were then placed into separate circles on a disposable slide. The slide was then centrifuged at 80–100 rpm for 2 min, and the titre (the highest dilution showing positive result or lowest detection point) then established as 0.2 mg/L (values of <0.2 were regarded as 0.1 mg/L).

The Young Men’s Christian Association submaximum cycle ergometry test protocol was used to assess the patients’ aerobic power, as described previously [23,24]. This protocol uses two to four 3-min stages of continuous exercise, with two heart rate (HR)-power output data points needed (steady state HR) of 110–150 beats/min. The two steady-state HR were plotted against the respective workload and a straight line drawn through the two points and extended to the patient’s predicted maximum HR (HRmax, 220 − age). The point at which the diagonal line intersects the horizontal line of predicted HRmax represents the maximum working capacity for the patient. A perpendicular line from this point to the baseline gives the maximum physical workload capacity, in kg/m/min, used to predict the patient’s VO2max. This procedure was done both before and after a stress test.

The continuous training group exercised on a bicycle ergometer at a low intensity of 35–59% of their HRmax reserve [25]. The starting workload was 100 kg (17 W) which was increased at a pedal speed of 50 rpm to obtain a HRmax reserve of 35%, and was increased in the first 2 weeks to a level of 59% HRmax reserve throughout the remaining part of the training period. The initial exercise session was increased from 45 min in the first 2 weeks of training up to 60 min throughout the remaining part of the training. The exercise session of three times per week was maintained throughout the 8-week period of training for continuous group. The control group were instructed not to undertake any vigorous physical activity during the period of study. At the end of the 8-week training period all men were asked to stop methyldopa and prescribed placebo tablets in a single-blind method for 1 week as a second wash-out period. Immediately after this wash-out period, fasting blood samples were collected, as described [21].

Descriptive statistics (mean and sd) were used for the patient’s physical characteristics, and the independent Student’s t-test (for continuous variables SBP, DBP, white cell count and VO2max) and Mann–Whitney U-test (ordinal CRP and IIEF scores) were used to assess the significance of differences. The t-test was also use to assess the difference before and after testing (change score). Spearman correlation was also used. In all tests P < 0.05 was considered to indicate statistical significance.

RESULTS

The age range of the patients was 50–70 years; the mean (sd) age of the exercise and sedentary groups was 61.8 (7.79) and 64.0 (8.53) years. The mean BP and VO2max before and after treatment for the two groups are shown in Table 1, and Fig. 1 shows the significant negative correlation between changes in CRP and IIEF score (r = −0.534).

Table 1. 
The changes in BP, CRP, VO2max and IIEF scores in response to exercise
Mean (sd)BeforeAfterP
Exercise   
SBP167.6 (11.62)153.43 (12.99)<0.05
DBP101.5 (7.51) 95.43 (9.25)<0.05
Control   
SBP159.6 (13.23)162.0 (15.60) 
DBP 97.2 (2.94) 96.1 (2.94) 
VO2max 23.12 (8.40) 29.83 (10.5) 
 Groups changed scores 
VO2max  <0.05
IIEF  <0.05
CRP  <0.05
Figure 1.

The correlation between changes in CRP and IIEF score after training.

DISCUSSION

The purpose of the present study was to determine the role and effect of continuous exercise on the association of CRP and ED in older hypertensive men with ED. The results indicate a significant effect of exercise on ED, and a significant negative correlation between CRP and ED after aerobic exercise.

These results agree with those in several studies [26,27] reporting a significant reduction in CRP after aerobic exercise, and an inverse correlation between CRP and VO2max in healthy subjects, and patients with mild-to-moderate hypertension or coronary heart disease. Several other studies of large populations, including the British Regional Heart Study [28], the Third National Health and Nutrition Examination Survey [29,30], the Cardiovascular Health Study [31], the men’s Health Professionals Follow-up Study, the Nurses’ Health Study II [32] and the Health, Ageing and Body Composition Study (Health ABC) [33], provide evidence for an inverse, independent dose-response relation between plasma CRP concentration and level of physical activity in both men and women.

The physiological basis for the therapeutic role of continuous exercise in the management of both ED and hypertension, as reported in the present study, could be related to the biochemical, neural and hormonal changes in the blood vessel walls that induce an acute and long-term blood vessel relaxation. The blood vessels might relax after each exercise session because of body-warming effects; local production of certain chemicals, such lactic acid and NO; decreases in nerve activity; and changes in certain hormones and their receptors [34,35]. Over time, as the exercise is repeated, there is growing evidence of a prolonged effect. Chronic (regular, long-term) physical training might reduce basal concentrations of inflammatory markers; data from cross-sectional observational studies have shown an inverse association between markers of systemic inflammation and physical activity and fitness status [28–33,36].

The present results show that continuous exercise improves erectile function in older hypertensive men with ED. This improvement was associated with an amelioration of endothelial function through a reduction in the marker (CRP) of systemic vascular inflammation.

CONFLICT OF INTEREST

None declared.

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