Men

The mechanism of action of nitrogen monoxide in the blood supply of genitals, and consequently, the strength of erection and orgasm, and the proceeds equally among women and men. The amino acid L-arginine of biochemical reactions – a precursor of Nitric Oxide – a beneficial effect on prostate health, this “second” man’s heart, the production and sperm quality, increases blood flow to the genitals, allowing for a more stable and prolonged erections for a more pronounced orgasm. Improvement of spermatogenesis, orgasm, libido in men solves the problem of certain types of male infertility, but it is a very hot topic in today’s life. According to statistics, more than 50% of cases of infertility in the pair accounted for by men. Improvement of blood circulation in the pelvis, which occurs at the level of microcirculation, preventing stagnation of blood – all that prevents the occurrence of prostatitis, adenoma, prostate cancer, hemorrhoids, varicose veins, or makes existing problems with these bodies.

 

Department of Urology and Institute for Sexual Medicine, Boston University School of Medicine, Boston, MA 02118, USA.

The NO-cGMP pathway plays a key role in the male and female genital sexual arousal response. Nitric oxide synthase (NOS) utilizes L-arginine and oxygen as substrates to produce nitric oxide (NO) and citrulline. Arginase is a metalloenzyme that catalyzes the hydrolysis of L-arginine to produce L-ornithine and urea. It is proposed that arginase competes for L-arginine and reduces NOS activity in genital tissues, thus modulating sexual function. Using 2 transition state analogue inhibitors of arginase, 2(S)-Amino-6-boronohexanoic acid (ABH) and S-(2-boronoethyl)-L-cysteine (BEC), we have characterized arginase activity in penile and vaginal tissue. Neither of these inhibitors has activity against NOS. Thus, ABH and BEC are useful compounds for examining the role of arginase in genital tissue physiology, without directly influencing NOS activity. We present data to suggest that arginase may regulate NO production by competing for endogenous pools of L-arginine. In this fashion, arginase is an indirect regulator of penile and vaginal blood flow and specific arginase inhibitors may improve genital blood flow during sexual arousal. As evidenced by the upregulation of arginase in specific disease states, its distribution in the vagina, and its modulation by sex steroid hormones, this enzyme may also participate in numerous other physiological and pathophysiological processes, such as tissue growth, fibrosis, and immune function

 

The Pyrah Department of Urology, St James’s University Hospital, Beckett Street, Leeds, LS18 4AW, UK. j.Cartledge@ukgateway.net

The functional state of the penis, flaccid or erect is governed by smooth muscle tone. Sympathetic contractile factors maintain flaccidity whilst parasympathetic factors induce smooth muscle relaxation and erection. It is generally accepted that nitric oxide (NO) is the principal agent responsible for relaxation of penile smooth muscle. NO is derived from two principal sources: directly from non-adrenergic non-cholinergic parasympathetic nerves and indirectly from the endothelium lining cavernosal sinusoids and blood vessels in response to cholinergic stimulation. The generation of NO from L-arginine is catalysed by nitric oxide synthase (NOS). There has been controversy over the relative prevalence of endothelial or neuronal NOS within the penis of different animal species. This review examines the role of NO in the penis in detail. Established and new treatments for erectile dysfunction whose effects are mediated via manipulation of the NO pathway are also described.

Department of Pharmacology, Shiga University of Medical Science, Otsu, Japan. n.toda.toyama-bldg@orion.ocn.ne.jp

The discovery of nitric oxide (NO) as an intercellular messenger or neurotransmitter opened a new era for identifying the important mechanisms underlying physiological and pathophysiological events in autonomically innervated organs and tissues; it also provided the way for development of new therapeutics based on a novel concept of molecule and cell interaction. Endothelium-derived relaxing factor (EDRF) discovered by Furchgott and Zawadzki has been proved to be NO, a labile gaseous molecule, that modulates vascular tone, platelet aggregation and adhesion, and vascular smooth muscle proliferation. Later, NO was determined to act as a non-adrenergic, non-cholinergic (NANC) neurotransmitter of postganglionic parasympathetic nerve fibers, innervating a variety of smooth muscles including the penile corpus cavernosum (CC). The nerve is called “nitrergic” or “nitroxidergic”. Although CC sinusoidal endothelial cells also produce and liberate NO in response to chemical and possibly physical stimuli, roles of neurogenic NO in penile erection appear to be more attractive and convincing. NO is formed from L-arginine via catalysis by NO synthase (NOS) isoforms, neuronal (nNOS), endothelial (eNOS), and inducible NOS. NO from nerves and possibly endothelia plays a crucial role in initiating and maintaining intracavernous pressure increase, penile vasodilatation, and penile erection that are dependent on cyclic GMP synthesized with activation of soluble guanylyl cyclase by NO in smooth muscle cells. Erectile dysfunction (ED) is caused by a variety of pathogenic factors, particularly impaired formation and action of NO. Thus, replenishment of this molecule or intracellular cyclic GMP is expected so far to be the most promising therapeutic measures for patients with ED. This article includes recent advances in research on physiological roles and pathophysiological implications of NO in penile erection and on novel therapy for ED in reference to NO.

 

Department of Urology, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

OBJECTIVES: To determine, in a prospective randomized, double-blind placebo-controlled study, the effect of 6 weeks of high-dose (5 g/day) orally administered nitric oxide (NO) donor L-arginine on men with organic erectile dysfunction (ED). PATIENTS AND METHODS: The study included 50 men with confirmed organic ED who were randomized after a 2-week placebo run-in period to receive L-arginine or placebo. A detailed medical and sexual history, O’Leary’s questionnaire, a specially designed sexual function questionnaire and a sexual activity diary were obtained for each patient. All participants underwent a complete physical examination including an assessment of bulbocavernosus reflex and penile haemodynamics. Plasma and urine nitrite and nitrate (designated NOx), both stable metabolites of nitric oxide, were determined at the end of the placebo run-in period, and after 3 and 6 weeks. RESULTS: Nine of 29 (31%) patients taking L-arginine and two of 17 controls reported a significant subjective improvement in sexual function. All objective variables assessed remained unchanged. All nine patients treated with L-arginine and who had subjectively improved sexual performance had had an initially low urinary NOx, and this level had doubled at the end of the study. CONCLUSIONS: Oral administration of L-arginine in high doses seems to cause significant subjective improvement in sexual function in men with organic ED only if they have decreased NOx excretion or production. The haemodynamics of the corpus cavernosum were not affected by oral L-arginine at the dosage used.

Seminological Laboratory SBALAG, Maichin Dom, Sofia, Bulgaria. rstanik@abv.bg

Penile erection requires the relaxation of the cavernous smooth muscle, which is triggered by nitric oxide (NO). We investigated the possibility of overcoming erectile dysfunction (ED) by increasing the amounts of endogenous NO. For this purpose, we orally administered Pycnogenol, because it is known to increase production of NO by nitric oxide syntase together with L-arginine as substrate for this enzyme. The study included 40 men, aged 25-45 years, without confirmed organic erectile dysfunction. Throughout the 3-month trial period, patients received 3 ampoules Sargenor a day, a drinkable solution of the dipeptide arginyl aspartate (equivalent to 1.7 g L-arginine per day). During the second month, patients were additionally supplemented with 40 mg Pycnogenol two times per day; during the third month, the daily dosage was increased to three 40-mg Pycnogenol tablets. We obtained a sexual function questionnaire and a sexual activity diary from each patient. After 1 month of treatment with L-arginine, a statistically nonsignificant number of 2 patients (5%) experienced a normal erection. Treatment with a combination of L-arginine and Pycnogenol for the following month increased the number of men with restored sexual ability to 80%. Finally, after the third month of treatment, 92.5% of the men experienced a normal erection. We conclude that oral administration of L-arginine in combination with Pycnogenol causes a significant improvement in sexual function in men with ED without any side effects.

Thorne Research, PO Box 25, Dover, ID 83825. duffy@thorne.com

Erectile dysfunction affects 50 percent of men ages 40-70 in the United States and is considered an important public health problem by the National Institutes of Health. Consumers are exposed to a plethora of natural products claiming to restore erection and sexual vitality. A review of the available empirical evidence reveals most naturally occurring compounds lack adequate clinical trials to support efficacy. However, arginine, yohimbine, Panax ginseng, Maca, and Ginkgo biloba all have some degree of evidence they may be helpful for erectile dysfunction. Improvements in penile endothelial L-arginine-nitric oxide activity appear to be a unifying explanation for the actions of these naturally occurring agents.