Effect of sodium nitroprusside on hemodynamics of corpus cavernosum in Chinese

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

Department of Urology, Shanghai Ninth People's Hospital, Shanghai Second Medical University, Shanghai 200011, China

Asian J Androl  2001 Dec; 3: 311-313

Keywords:  hemodynamics; corpus cavernosum; nitric oxide; Doppler ultrasonography; erectile dysfunction

Abstract

Aim: To study the effect of sodium nitroprusside (SNP) on the hemodynamics of corpus cavernosum in Chinese men with erectile dysfunction (ED). Methods:  In 68 ED patients receiving intracavernous injection (ICI) of SNP, the cavernous hemodynamics were studied by Doppler ultrasonography. Results:  The peak flow velocity (PFV), the artery diameter (Ad), the mean velocity of arterial blood (MV) and the vein diameter (Vd) were significantly higher after ICI of SNP than before ICI, but the end diastolic velocity (EDV) did not change significantly. Conclusion:  The increase in Vd after SNP suggests that the venous outflow is not invariably decreased during penile erection.

1 Introduction

Erectile dysfunction (ED) is a common disease for men. Recent studies suggest that the nonadrenergic-noncholinergic innervation is the principal mechanism responsible for vascular relaxation at the cavernous smooth muscle^[1]. Sodium nitroprusside (SNP) is a nitric oxide (NO) donor and, therefore, stimulator of the cyclic guanosine monophosphate pathway. In vitro study indicated that NO induced a concentration-dependent relaxation of the penile vessel and cavernous tissue of canine^[2]. SNP was originally used as an antihypertensive agent^[3] and was recently employed for the treatment of ED through intracavernous injection (ICI). SNP hasseveral benefits over prostaglandin E₁ for intracavernous use, such as lower cost, absence of local pain and shorter action, allowing detumescence after orgasmand a lower risk of priapism^[4]. In a previous report^[5] the authors indicated that in Chinese patients with ED, SNP effectively increased the penile length, circumference and hardness in a sufficient duration of time without apparent side effect. In the present paper the effect of SNP on the hemodynamics of corpus cavernosum in Chinese men with ED was evaluated.

2 Subjects  and  methods

2.1 Patients

From September 1996 to October 2000, 68 patients with ED, aged 27-65 (averaging 43.5) years, entered the study. Patients received a general physical examination and specific laboratory examinations, including blood testosterone, prolactin, estradiol, FSH, LH and glucose. All these data should be within the normal limit to exclude ED due to endorinopathic causes. In all the patients the nocturnal penile tumescence was normal.

2.2 SNP injection

An appropriate dose of 300 g was injected intracavernously. A tourniquet was placed at the base of the penis before each injection and was removed 5 min after ICI. A fine needle should be used with a slender graduated syringe that allows accurate and slow injection of SNP. The injection is made into the lateral aspect of the penis. After the removal of the needle, a firm pressure should be applied  to the injection site for 5 min. Erection will usually be developed in 5 to 10 min.

2.3 Hemodynamic evaluation

The hemodynamics of corpus cavernosum was evaluated with an AU4 Duplex Ultrasonograph (Biosound, USA) before ICI and 10 min after ICI according to the method described by Eardley & Krishna^[6]. Both the cavernosal artery providing most blood supply to the spongy tissue and the deep dorsal vein draining the spongiosal vein and the bulbar vein, were investigated. Study parameters included the peak flow velocity (PFV), the end diastolic velocity (EDV), the artery diameter (Ad), the vein diameter (Vd) and the mean velocity of arterial blood (MV).

2.4 Data processing

The data were expressed in meanSD. Statistical analysis was performed by the Student's t test and P<0.05 was considered significant.

3 Results  

3.1 Penile erection

After the administration of SNP, penile erection was produced in all the 68 patients with satisfactory increases in penile length, circumference, rigidity and duration of erection. Both the local and systemic side effects were negligible. For details please refer to Fu et al^[5].

3.2 Hemodynamic investigation

For the results of the hemodynamic investigation of the cavernosal artery and the deep dorsal vein with the Duplex Ultrasonograph, please refer to Table 1. It can be seen that the PFV, the Ad, the Vd and the MV are all significantly increased after the administration of SNP. Although the EDV is also increased, the difference is statistically insignificant. It is interesting to note that the diameter of the vein (Vd) was also significantly increased.

Table 1. Hemodynamic parameters in 68 patients (meanSD)

4 Discussion

Lue et al^[7] suggested the use of the high frequency ultrasound combined with the Doppler technology to analyze the blood flow in penile blood vessels; they also proposed the addition of color to the Duplex ultrasonography to facilitate identification. This enabled immediate recognition of the appropriate vessel and the easy identification of the proper Doppler angle. It soon became accepted as a useful method of assessment of patients with vasculogenic impotence.

The technique of performing color Duplex scanning is of prime importance and a standardized procedure should be employed^[6]. It is a usual practice to scan vessels as proximally as possible and, following intracavernosal injection, repeated measurements of the velocity should be made until the PFV is achieved.

Nitric oxide is synthesized from L-arginine by the action of the nitric oxide synthase (NOS). Nitric oxide stimulates the enzyme guanylate cyclase which converts guanosine triphosphate to cyclic guanosine monophosphate. This in turn stimulates proteinkinase G to close the L-type calcium channel and open the potassium channel. Both will result in a fall in the cytoplasmic calcium ion concentration and smooth muscle relaxation^[8-10]. Ignarro et al^[11] documented that NO induced relaxation of the corpus cavernous smooth muscle. Lugg et al^[12] suggested the presence of a NO-dependent pathway in corpus cavernosum. Many physiological systems and certain pharmacological agents regulate the synthesis of NO in animals and humans.

In the present study, SNP apparently relaxes the cavernosal helicine artery and the deep dorsal vein. The extent of relaxation seems to be related to the quantity of NOS fibers present in the blood vessels in consideration. A rise in the PFV and the Ad after ICI of SNP assure an increase in the arterial inflow (MV).

Recent studies suggest that during erection the helicine arteries are dilated, thereby filling the sinusoidal spaces, which in turn compress the subtunical venous plexuses against the tunica albuginea, resulting in reduced venous outflow during erection^[13]. However, in our study, the diameter of the deep dorsal vein was increased by SNP as well, suggesting that at the erection phase the venous outflow is not invariably decreased. Further studies are needed for the clarification of this point.

References

[1] Ishii N, Watana H, Irisawa C, Kikuchi Y, Kubota Y, Kawamura S, et al. Intracavernous injection of prostaglandin E₁ for the treatment of erectile impotence. J Urol 1989; 141: 323-8.
[2] Gao B, Xue ZY. Nitric oxide induced relaxation of isolated canine blood vessel and cavernous smooth muscle. Chin J Urol 1996; 17: 109-13.
[3] Azadzai KM, Goldstein I, Siroky MB, Traish AM, Krane RJ, Saenz de Tejada I. Mechanisms of ischemia-induced cavernosal smooth muscle relaxation impairment ina rabbit model of vasculogenic erectile dysfunction. J Urol 1998; 160 (6 Pt 1):2216-22.
[4] Martinez-Pineiro L, Lopez-Tello J, Alonso Dorrego JM, Cisneros J, Cuervo E, Martinez-Pineiro JA. Preliminary results of a comparative study with intracavernous sodium nitroprusside and prostaglandin E1 in patients with erectile dysfunction. J Urol 1995; 153: 1487-90.       
[5] Fu Q, Yao DH, Jiang YQ. A clinical comparative study on effects of intracavernous injection of sodium nitroprusside and papaverine/phentolamine in erectile dysfunction patients. Asian J Androl 2000; 2: 301-3.
[6] Eardley I, Krishna S, editors. Erectile dysfunction. Leeds, UK:  Mosby-Wolfe Medical Communications; 1998. p 39.
[7] Lue TF, Hricak H, Marich KW. Vasculogenic impotence evaluated by high-resolution ultrasonography and pulsed Doppler analysis. Radiology 1985; 155: 77-80.
[8] Chuang AT, Strauss JD, Murphy RA, Steers WD. Sildenafil, a type-5 CGMP phosphodiesterase inhibiter, specifically amplifies endogenous cGMP-dependent relaxation in rabbit corpus cavernosum smooth muscle in vitro. J Urol 1998; 160: 257-61.
[9] Gupta S, Salimpour P, Saenz de Tejada, Daley I, Gholami S, Daller M, et al. A possible mechanism for alteration of human erectile function by digoxin:  inhibition of corpus cavernosum sodium/potassium adenosine triphosphatase activity. JUrol 1998; 159: 1529-36.
[10] Hass CA, Seftel AD, Razmjouei K, Ganz MB, Hampel N, Ferguson K. Erectile dysfunction in aging: upregulation of endothelial nitric oxide synthase. Urology 1998; 51: 516-22.
[11] Ignarro LJ, Bush PA, Buga GM, Wood KS, Fukuto JM, Rajfer J. Nitric oxide and cyclic GMP formation upon electrical field stimulation cause relaxation of corpus cavernous smooth muscle. Biochem Biophys Res Commun 1990; 170: 843-8.
[12] Lugg JA, Gonzalea-Cadavid NF, Rajfer J. The role of nitric oxide in erectile function. Andrologia 1995; 16: 2-6.
[13] Jonas WF, editor. Erectile dysfunction. Berlin:  Springer-Verlag Publisher; 1991. p 223-8.

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Correspondence to:  Dr Qiang FU, Department of Urology, Shanghai Ninth People's Hospital, Shanghai Second Medical University, Shanghai 200011, China.
Tel: +86-21-6313 8341 ext 5116            Fax:  +86-21-6313 6856                                     
E-mail: jamesqfu@yahoo.com.cn
Received 2001-07-16                            Accepted 2001-12-03