:: Asian Journal of Andrology ::

A clinical comparative study on effects of intracavernous injection of sodium nitroprusside and papaverine/phentolamine in erectile dysfunction patients

Qiang FU, De-Hong YAO, Yue-Qin JIANG

Department of Urology, the Ninth Peoples Hospital, Shanghai Second Medical University, Shanghai 200011, China

Asian J Androl 2000 Dec; 2: 301-303

Keywords: erectile dysfunction; intracavernous injection; sodium nitroprusside; nitric oxide

Abstract

Aim: To study the effect of intracavernous sodium nitroprusside (SNP), a nitric oxide (NO) donor, on penile erection. Methods: Forty-two patients with erectile dysfunction (ED) were randomly assigned to receive SNP 300 g or the control drugs (papaverine 30 mg + phentolamine 1 mg) intracavernously crosswise one week apart. The penile length, circumference and hardness after the administration of the experimental and control drugs were assessed and compared statistically. Results: (1) There was no significant difference between the changes in penile length and circumference in the two occasions; (2) In 25 SNP and 28 control cases, the hardness of the penis was scored above 100 as evaluated by the Virag method (P>0.05); (3) The duration of erection in the controls was longer than that in the SNP, but there were three priapism in the controls and not a single one in the SNP; (4) there was no apparent change in the heart rate and blood pressure in both occasions; other side effects were minimal except slight local pain in a few controls. Conclusion: SNP facilitates relaxation of the penile smooth muscle and penile erection without significant side effects. SNP may be used in ED patients that experience pain and priapism with papaverine/phentolamine.

1 Introduction

Intracavernous injection of vasoactive drugs has been an important measure in the diagnosis and treatment of erectile dysfunction (ED). The most common drugs used are papaverine^[1, phentolamine^[2, prostaglandin E^[3], or a combination of them, but all these approaches are associated with undesirable side effects, such as priapism, pain after injection , cavernous fibrosis, etc.

Recent in vivo and in vitro studies suggested that non-adrenergic, non-cholinergic relaxation of the cavernous smooth muscle is mediated by nitric oxide (NO) through the activation of the guanosine monophosphate pathway^[4]. In several animal species, the intravenous injection of sodium nitroprusside (SNP), a NO donor, caused a dose-dependent increase in cyclic guanosine monophosphate in the smooth muscle and induced penile erection^[5].

SNP is commonly used as an antihypertensive agent^[6]. The present paper evaluates the efficacy of SNP in the management of ED in a parallel comparative study with papaverine + phentolamine (control drugs) in 42 ED patients.

2 Materials and methods

2.1 Patients

Forty-two ED patients, aged 27-65 (mean: 43.5) years, visiting this Department from January 1997 to December 1999 entered the study. As a part of the routine diagnostic evaluation for ED every patient received general physical check up and various laboratory examinations, including the determination of serum testosterone, prolactin, estradiol, FSH, LH and glucose. All these data was to be within the normal range to exclude neurogenic and endocrinopathic ED. In all the patients, the nocturnal penile tumescence was normal.

2.2 Drugs and doses

The dose levels for SNP was 300 g and those for the control drugs: papaverine 30 mg and phehtolamine 1 mg. All the patients received intracavernous injection of one dose each of SNP and the control drugs one week apart. The drug(s) used for the first administration was(were) determined at random.

Before injecting sodium nitroprusside, it was important to place a tight rubber band at the base of the penis to avoid rapid dispersal of drug to the systemic circulation resulting in subsequent arterial hypotension.

2.3 Evaluation of penile erection

The penile length, circumference, rigidity and duration of erection were assessed before and after the use of drugs as follows:
(a) Penile length: measured from the basement of penis to the meatus.
(b) Penile circumference: measured at the coronary sulcus.
(c) Penile rigidity: assessed according to the method of Virag^[7].
(d) Duration of erection: from the commencement of rigidity to detumescence.

2.4 Side effects

Fifteen minutes before and after the administration of drug, the pulse and blood pressure were measured and remevant signs and symptoms observed.

2.5 Data analysis

Statistical analysis of the differences was performed with the Student's t test. P<0.05 was considered significant.

3 Results

3.1 Penile erection in all the 42 patients received either SNP or papaverine+phehtolamine

(a) Penile length and circumference:

SNP: length increased by 4.751.45 cm; circumference by 2.591.65 cm. Control drugs: length increased by 4.001.80 cm; circumference by 2.712.05 cm. There was no significant difference between the corresponding values of the two occasions (P>0.05).

(b) Penile rigidity:

All patients were scored above 10 according to the method of Virag (Table 1); with SNP 25 patients (59.5%) were above 100 and with the control drugs, 28 patients (66.7%). No significant difference was found between the corresponding figures of the two occasions (P>0.05).

SNP: 24.237.96 (15-45) minutes. Control drugs: 37.68 15.36 (20-55) minutes. The difference was significant (P<0.01).

Table 1. Number of patients with different Virag points after SNP and control drugs.

Virag point	SNP	Papaverine + phentolamine
10	0	0
1030	2	3
3050	6	4
5075	6	3
75100	3	4
100	25 (59.5%)	28 (66.7%)

3.2 Side effects

(a) Priapism occurred in 3 cases after injection of the control drugs, so that aspiration of blood from the corpus cavernosum and/or aramine should be employed to combat this condition. There was no priapism in SNP.

(b) Local pain occurred in 15 cases after the administration of the control drugs, but not a single one after SNP.

4 Discussion

The mechanism for penile erection is very complicated. The intracavernous application of SNP in ED is related to the neuro-transmitter hypothesis that is of a high concern in the medical circle. Penile erection involves the adequate relaxation of the cavernous smooth muscle. Nonadrenergic and noncholinergic fibers that form a part of the cavernous nerve are responsible for inducing selective smooth muscle relaxation of the cavernous tissue.

Vasoactive intestinal peptide^[8], prostaglandin E-₁[9] and calcitonin gene-related peptide^[10] were initially proposed as possible mediators for erection. Recent investigations, however, have shown that nitric oxide generated in response to nonadrenergic and noncholinergic stimulation is the main event leading to vascular smooth muscle relaxation through activation of the soluble guanylate cyclase^[11,12]. It causes an increase in the intracellular concentration of cyclic guanosine monophosphate and induces relaxation by activating cyclic guanosine monophosphate-dependent proteinkinase, which inactivates the light chain myosin kinase and decreases cytosolic calcium concentration^[13]. Sodium nitroprusside which is an NO donor has been used clinically as an antihypertensive agent for many years. Nitric oxide also inhibits platelet aggregation and adhesion to endothelial surfaces, preventing thrombosis of stagnant blood in sinusoidal spaces during erection. In this study it was shown that SNP 300 g had a similar effect as papaverine/phentolamine (30 mg/1 mg), which were sufficient to induce good erection in the majority of patients. The result is similar to that reported by Martinez-Pineiro et al^[14], who compared the efficacy of SNP with prostaglandin E₁. We did not observe any hypotensive episode as described by other scientists^[15]. No one complained of palpitation and dizziness. Due to its shorter half-life of nitric oxide, erection with sodium nitroprusside is of shorter duration than with papaverine/phentolamine, but it seems to be more physiological.

References

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Correspondence to: Dr. Qiang FU, Dept. of Urology, the Ninth People's Hospital, Shanghai 200011, China.
Tel: +86-21-6313 8341 Ext. 5116 or 5117
e-mail: james-fu@citiz.net
Received 2000-08-07 Accepted 2000-11-23