Methods and Findings in Experimental and Clinical Pharmacology
Vol. 24, Suppl. A, 2002, pp. 65-66
ISSN 0379-0355
Copyright 2002 Prous Science, S.A.
CCC: 0379-0355/2002
http://www.prous.com

Resistance Arteries and Erection

A. García Sacristán

Department of Physiology, Faculty of Pharmacy, U.C.M., Madrid, Spain

Vascularizaiton of the penis arises from the terminal branches of the internal pudendal artery, which originates in the pelvis from the internal iliac artery. After branching to the perineal artery in Alcock's canal, it becomes the common penile artery which, before reaching the cavernous bodies, divides into four terminal branches: dorsal, cavernosal, bulbar and urethral arteries. The cavernosal or deep artery enters the tunica albuginea in the proximal cavernous bodies. Once within the tunica, it divides into multiple tortuous terminal branches called helicine arteries, which open directly into the lacunar spaces. The helicine arteries act as resistance arteries, being tortuous in the flaccid state and straight during erection (1).

The penile vessels and erectile tissues are innervated by the autonomic nervous system. Stimulation of the sacral parasympathetic nerves induces erection by increasing arterial blood flow, sinusoid relaxation and increased venous resistance. Stimulation of the lumbar sympathetic nerves causes penile vasoconstriction (2).

Locally, penile detumescence is mediated by adrenergic nerve endings. This adrenergic stimulation causes vasoconstriction of the penile arteries and contraction of the trabecular muscle, which leads, respectively, to reduced arterial blood flow and collapse of the lacunar spaces. The contraction of the trabecular muscle causes decompression of the cavernous bodies' drainage venules, enabling venous drainage of the lacunar spaces. The penile resistance arteries have a functional adrenergic innervation, mediated by a₁- and a₂-adrenergic receptors, with a contractile action (3), which would confirm the vasoconstrictive activity of the sympathetic nervous system.

Histochemical studies have revealed NAPH-d-positive activity both at the adventitia-media interface and in the endothelial cells, which indicates the presence of nitric oxide (NO) in the penile resistance arteries (4). Using in vitro physiopharmacological techniques, it has been found in the helicine arteries that the NO synthesis inhibitor, N^G-nitro-l-arginine (l-NOARG), inhibits electrically elicited relaxations, an effect that is antagonized in the presence of l-arginine (5). Therefore, NO is the mediator of the neurogenic relaxation of the penile resistance arteries through guanylate cyclase activation. This in turn increases the cGMP levels, facilitating the opening of the high conductance, Ca²⁺-activated K⁺ channels and causing hyperpolarization and relaxation of these arteries (4, 5). This relaxing action by NO is inhibited by stimulation of the presynaptic a₂-adrenergic receptors (6). In addition to being synthesized by the nitrergic nerves, NO can be synthesized by the helicine arteries' endothelial cells, from where it is released by the action of endothelium-dependent vasodilative substances such as acetylcholine and bradykinin. These substances also stimulate synthesis and release of a nonNO, non-prostanoid hyperpolarizing factor (EDHF), which relaxes the muscle cells by activating the K⁺ channels and the Na⁺-K⁺ ATPase pump (7).

The cavernoso-veno-occlusive mechanism plays a basic role in penile erection and distension. A number of studies suggest that an active veno-occlusive mechanism, in addition to the known passive vein compression mechanism caused by distension of the venous sinusoids, must be taken into account. Thus, the presence of a-adrenergic receptors and H₁ histamine receptors (9) has been shown in penile veins.

NO synthesis is directly regulated by the oxygen concentration to which the cavernous body is exposed. Both oxygen and l-arginine are necessary for NO synthesis mediated by the enzyme nitric oxide synthase (NOS). The partial oxygen pressure (PO₂) in the blood in the cavernous body during the flaccid state is similar to the PO₂ in venous blood (35 mmHg). However, during erection, due to the increased blood flow following vasodilatation of the penile arteries, the blood in the cavernous body attains a PO₂ of approximately 100 mmHg. With the low oxygen concentrations existing in the cavernous body when the penis is flaccid, NO synthesis would be inhibited, thereby preventing endothelium-dependent and nitrergic nerve-induced relaxation of the trabecular muscle (10). On the contrary, after arterial vasodilatation, the oxygen concentration in the cavernous bodies increases, with the result that there is now sufficient oxygen for NO synthesis. These facts would explain why different vascular disorders, either directly or as a result of their treatment, cause erectile dysfunction, due to the decreased local blood flow during these processes, not enough blood--and, with it, oxygen--enters the penis. This, in turn, would lead to an inability to generate penile vasodilatation and distension of the cavernous bodies due to lack of NO.

REFERENCES

1. Andersson K.E., Wagner, G. Physiology of penile erection. Physiol Rev 1995, 75: 191-236.

2. Lue, T.F., Tanagho, E.A. Physiology of erection and pharmacological management of impotence. J Urol 1987, 137: 829-36.

3. Simonsen, U., Prieto, D., Hernández, M., Saenz de Tejada, I., García Sacristán, A. Adrenoceptor-mediated regulation of the contractility in horse penile resistance arteries. J Vasc Res1997, 34: 90-102.

4. Simonsen, U., Prieto, D., Saenz de Tejada, I., García Sacristán, A. Involvement of nitric oxide in the non-adrenergic, non-cholinergic neurotransmission of horse deep penile arteries: Role of charybdotoxin-sensitive K⁺- channels. Br J Pharmacol 1995, 116: 2582-90.

5. Simonsen, U., Prieto, D., Delgado, J.A. et al. Nitric oxide is involved in the inhibitory neurotransmission and endothelium-dependent relaxations of human penile resistance arteries. Clin Sci 1997, 92: 269-75.

6. Simonsen, U., Prieto, D., Hernández, M., Saenz de Tejada, I., García Sacristán, A. Prejunctional a₂-adrenoceptors inhibit nitrergic neurotransmission in horse penile resistance arteries. J Urol 1997, 157: 2356-60.

7. Prieto, D., Simonsen, U., Hernández, M., García Sacristán, A. Contribution of K⁺ channels and ouabain-sensitive mechanisms to the endothelium-dependent relaxations of the horse penile small arteries. Br J Pharmacol 1998, 123: 1609-20.

8. Kirkeby, H.J., Fahrenkrug, J., Holmquist, F., Ottesen, B. Effects of noradrenaline, 5-hydroxytriptamine and histamine on human penile cavernous tissue and circumflex veins. Int J Impot Res 1989, 1: 181-8.

9. Martinez, A.C., Prieto, D., Hernández, M., García Sacristán, A., Benedito, S. Contractile response of horse deep dorsal penile vein to histamine. Int J Impot Res 2002, 14: 85-92.

10. Kim, N., Vardi, Y., Padma-Nathan, H., Daley, J., Goldstein, I., Saenz de Tejada, I. Oxygen tension regulates the nitric oxide pathway: Physiological role in penile erection. J Clin Invest 1993, 91: 437-42.

Methods and Findings in Experimental and Clinical Pharmacology Vol. 24, Suppl. A, 2002, pp. 65-66
ISSN 0379-0355 Copyright 2002 Prous Science, S.A. CCC: 0379-0355/2002 http://www.prous.com