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Effect of sildenafil citrate on penile erection of rhesus macaques

Xun-Bin Huang, Cheng-Liang Xiong, Cheng-Gao Yu, Jie-Ling Zhou, Ji-Yun Shen

Center for Reproductive Medicine, Tongji Medical College, Huazhong University of Science and Technology, 13 Hang Kong Road, Wuhan 430030, China

Asian J Androl 2004 Sep; 6: 233-235


Keywords: sildenafil; rhesus macaque; electromyogram; corpus cavernosum; penile erection
Abstract

Aim: To examine the effect of sildenafil citrate on penile erection of male rhesus macaque. Methods: Twenty Macaca mulatta were divided into the sildenafil treated and the control groups of 10 animals each. The penile size, the corpus cavernosal electromyogram (EMG) and the intra-corpus cavernosal pressure (ICP) were determined. Results: The diameter of penis and the ICP were significantly increased and the corpus cavernosal EMG significantly reduced in the sildenafil group. Conclusion: Sildenafil citrate increases the penile size and ICP and reduces the corpus cavernosal EMG in male rhesus macaque.

1 Introduction

There are plenty of reports on clinical studies on sildenafil in erectile dysfunction (ED) in men [1, 2], however, animal experiments are scarce [3, 4]. The present paper was aimed at the effects of sildenafil on the penile size, the corpus cavernosal electromyogram (EMG) and the intra-corpus cavernosal pressure (ICP) in rhesus macaques.

2 Materials and methods

2.1 Animals

Twenty Chinese rhesus macaques (Macaca mulatta, provided by the Provincial Experimental Center of Non-human Primates, Fuzhou, China), weighing 5 - 11 kg, were randomly divided into 2 groups with 10 animals each.

2.2 Sildenafil

Sildenafil citrate (Viagra) 100 mg tablets were purchased from the Pfizer Pharmaceuticals, China. It was given orally at a dose of 4 mg dissolved in 0.2 mL distilled water (2 %).

2.3 Observation

Monkeys were anesthetized with ketamine, 10 mg/kg, i.m. and laid supine with limbs bending down at the edge of the operating table. Sildenafil or an equivalent volume of distilled water was dripped into the oral cavity. The length and diameter of the penis, the intra-corpus cavernosum pressure (ICP) and the electromyogram (EMG) of the corpus cavernosum were examined be fore and at 15, 30, 45 and 60 min after administration of Sildenafil. EMG was performed by attaching the reference electrode on the inner part of the thigh and the needle recording electrode into the corpus cavernosum at a 45o angle and a depth of 0.8 - 1.0 cm. Signals were amplified through a DC Preamplifier (Type F2G-1, Nanjing Liuhe Wireless Gadget Factory, China) and recorded through a self-poise recorder (Type XWT200, Shanghai No.2 Automechanism Factory, China). For ICP recording a needle electrode (gauge 8) was penetrated into the corpus cavernosum 1 - 1.5 cm away from the EMG electrode and connected to a pressure energy transformer (Type BPM-1, Baoji Wireless Factory, China) connected to a self-poise recorder (XWT200, Shanghai No. 2 Automatic Factory, Shanghai, China).

2.4 Statistical analysis

Data were processed by two factor ANOVA and P<0.05 was considered significant.

3 Results

3.1 Effect on penile size

The penile diameter increased significantly at 15 - 45 min after administration of sildenafil (P<0.05), Table 1.

Table 1. Effect of sildenafil on Penile diameter (mm, meanSD). bP<0.05, compared with controls.

Group

Dose
(mg/kg)

Pre- administration

Post-administration

15 min

30 min

45 min

60 min

Control

0

8.380.48

8.501.00

8.63 0.75

8.500.58

8.380.95

Sildenafil

4.0

8.250.29

9.501.73b

9.251.26b

9.631.60b

8.881.55

3.2 Effect on EMG and ICP

The EMG dropped significantly at 15 - 60 min after administration of sildenafil compared with the pre-treatment value (P<0.05 - 0.01, Table 2). The ICP in the sildenafil group was increased significantly (P<0.05, Table 3).

Table 2. Effect of sildenafil on EMG (mV, meanSD). bP<0.05, cP<0.01, compared with controls.

Group

Dose
(mg/kg)

Pre-
Administration

Post-administration

15 min

30 min

45 min

60 min

Control

0

350.0057.74

325.0095.74

350.00100.00

300.0081.65

337.50110.87

Sildenafil

4.0

625.00170.78

262.50197.38b

325.00170.78b

237.50205.65b

150.0057.74c

Table 3. Effect of sildenafil on ICP (cmH2O, meanSD). bP<0.05, compared with controls.

Group

Dose(mg/kg)

Pre-administration

Post-administration

15 min

30 min

45 min

60 min

Control

0

4.830.21

4.331.27

3.751.20

4.751.97

5.000.98

Sildenafil

4.0

5.350.91

7.384.41b

8.604.37b

7.885.56b

11.456.43b

4 Discussion

The present result shows that sildenafil significantly increases the penile diameters and the ICP with a reduction in the EMG of the cavernous body, which indicates relaxation of the corpus cavernosum smooth muscle. The most obvious evidence of ED is the absence of a fully expanded penis. Though the penile length do not show significant change before and after sildenafil, the latter significantly increases the penile diameter.

Recently, it was indicated that sildenafil enhanced penile erection upon electro-stimulation in rats and with sildenafil, penile erection could be induced by weaker stimuli [3]. Taher et al [4] showed that sildenafil relaxed diabetic penile smooth muscle of cynomolgus monkey in vitro. Sildenafil also relaxed the corpus cavernosum of rabbits in vitro [5].

The present study is the first report on the observation of the relaxation effect of sildenafil on the corpus cavernosum in vivo in the monkey, thus creating a model in non-human primate for the objective study of sildenafil effect.

Ketamine does not modify the vascular status of the corpus cavernosum as evidenced by the results of the control group. On the contrary, people tried to treat priapism with ketamine [6, 7], though not always effective [8]. Other researchers also used ketamine to anaesthetize rats while checking the ICP [9].

In conclusion, sildenafil citrate increases the penile size and ICP and reduces the corpus cavernosal EMG in male rhesus macaque.

References

[1] Jarow JP, Nana-Sinkam P, Sabbagh M, Eskew A. Outcome analysis of goal directed therapy for impotence. J Urol 1996;155: 1609-12.
[2] Goldstein I, Lue TF, Padma-Nathan H, Rosen RC, Steers WD, Wicker PA. Oral sildenafil in the treatment of erectile dysfunction. Sildenafil Study Group. N Engl J Med 1998; 14;338: 1397-404.
[3] Ueno N, Iwamoto Y, Segawa N, Kinoshita M, Ueda H, Katsuoka Y. The effect of sildenafil on electrostimulation-induced erection in the rat model. Int J Impot Res 2002; 14: 251-5.
[4] Taher A, Birowo P, Kamil ST, Shahab N. Relaxation effect of nitric oxide-donor on diabetic penile smooth muscle in vitro. Clin Hemorheol Microcirc 2000; 23: 277-81.
[5] Palea S, Barras M. Comparison of the relaxant effects of alfuzosin, phentolamine and sildenafil on rabbit isolated corpus cavernosum. BJU Int 2003; 91: 873-7.
[6] Davies C, Bailie R. Ketamine, treatment for unwanted penile turgescence. J R Army Med Corps 1991; 137: 106.
[7] Hutchinson WF. Persistent erection and general anaesthesia. Anaesthesia 1990; 45: 794.
[8] Nouri M, Nouri M, Tligui M, Sebe P, Haab F, Gattegno B, et al. Peroperative erection in lower urologic surgery. Prog Urol 2000; 10: 303-9.
[9] Rivas DA, Chancellor MB, Huang B, Salzman SK. Erectile response to topical, intraurethral and intracorporal pharmacotherapy in a rat model of spinal cord injury. J Spinal Cord Med 1995; 18: 245-50.


Correspondence to: Dr. Xun-Bin Huang, Center for Reproductive Medicine, Tongji Medical College, Huazhong University of Science and Technology, 13 Hang Kong Road, Wuhan 430030, China.
Tel: +86-27-8369 2651
E-mail: huangxb@mails.tjmu.edu.cn
Received 2003-09-12   Accepted 2004-05-19