CHAPTER ONE
INTRODUCTION
PHYSIOLOGY OF ERECTION
Penile Erection involves an integration of complex physiological processes involving the central nervous system, peripheral nervous system, hormonal and vascular systems. Any abnormality involving these systems whether from medications or disease has a significant impact on the ability to develop and sustain erection; ejaculate and experience orgasm. (Laumann et al., 1999).
The physiological process of erection begins in the brain and involves the nervous and vascular system. The chemicals that initiate erection are neurotransmitters present in the brain. Any kind of stimulation physical or psychological, causes nerves to send message to the vascular system which result in significant blood flow to the penis. Two arteries in the penis supply blood to erectile tissues and the corpora cavernous which become engorged and expand as a result of increased blood flow and pressures. Because blood must stay in the penis to maintain rigidity. An erectile tissue is enclosed by tunicae, which is fibrous elastic sheathes cinch which prevents blood leaving he penis during
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electron. When muscle in the penis contract to stop the inflow of blood and open out flow channels and an electron is reserved.
HORMONAL INVOLVEMENT IN ERECTION
ï‚· Oestrogen/Progesterone: (These are female hormones that cause clitoral
erection. If the body has two much oestrogen and or too little testost erone, she ca n get very wet but can not erect her clitoral and G-spot. ( Haimen et al., 2002). Estrogen tends to increase the size of the bread, labia minors (inner lips) and clitoral hood, but shrinks the glans clitoris into the clitoral hood making it invisible. It also increases the thickness of the vaginal lining making the G-spot inaccessible. The mechanism of the clitoral and G-spot erection is the same as that of the penis. It is driven by the parasympathetic sexual nerve (The neurotransmitter acetylcholine) through the neurotransmitter. Nitric oxide and the erection dilator cGMP, which is continuously powered by the burning of testosterone without a testosterone burst and burning. She cannot pop the glans Clitoris and G-spot out. If she is on birth control pills there is a chance that her body is over flooded by estrogens and low progesterone. Over loaded liver cannot produce sufficient essential enzymes to synthesize sufficient NO, cGMP and testosterone to support the clitoral and G-spot erection infact excessive estrogen or progesterone in the body will shrink the penis, clitoral and G-spot, but likely increase the breast size (under the excessive estrogen action).
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ï‚· Testosterone:- Testosterone is a hormone produced by the testicles and is responsible for the proper development of male sexual characters. The pump helps the penis to become erect while band maintains the erection.
Circulating levels of testosterone correlate with NO, production. Testosterone treatment can reduce central adiposity and insulin resistance, which may contribute to its beneficial effects on vascular NO, and ED. Raising low testosterone levels improves ED and can restore erectile function in response to PDE-5 inhibitors.
MECHANISM OF ACTION OF PDE-5 INHIBITION IN ERECTILE DYSFUNCTION.
A spinal reflex and the L-arginine nitric oxide guanglyl cyclase-cyclic guanosine monophonsphate (cGMP) pathway mediate smooth muscle relaxation that results in penile erection. Nerves and endothelial cells directly release nitric oxide in the penis, where it stimulates guanylyl cyclase to produce cGMP and lowers intracellular calcium level. This triggers relaxation of arterial and trabecular smooth muscle, leading to arterial dilation, venous constriction, and erection. Phosphodiesterases (PDEs) is the predominant phosphodiesterase in the corpus cavernosum. The catalytic site of PDE-5 normally degrades cGMP and PDE-5 inhibitors such as sildenafil potentiate endogenous increase in cGMP by inhibiting its breakdown at the catalytic site. Phosphorylation of PDE-5 increases its enzymatic activity as well as the affinity of its allosteric (noncatalytic/GAF domains) sites for cGMP. Binding of cGMP to the allosteric
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site further stimulates enzymatic activity. Thus phosphorlation of PDE-5 and binding of cGMP to the non catalytic site mediate negative feed back regulation of the cGMP pathway.
In recent years a deeper understanding of the regulation of penile smooth muscle has led to greater insight into the physiology of normal erectile function and erectile dysfunction (ED), as well as the introduction of phosphodiesterase (PDE) inhibitor for the treatment of ED. The oral PDE-5 inhibitors sidenafil has proved to be a safe and effective treatment for this disorder and has fostered further research into the underlying mechanisms of such drugs. This article will review the biochemical pathways involved in erection. The role of PDE-5 in these pathway and the molecular mechanisms involved in PDE activity.
A penile erection result from the relaxation of smooth muscle in the penis .the process is mediated by a spinal reflex and incorporates sensory and mental stimuli. The Balance between factors that stimulate contraction and relaxation determines the tone of penile vasculature and the smooth muscle of the corpus cavernosum.