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Physiological regulation of penile arteries and veins

Abstract

Recent experimental evidence suggests that arterial insufficiency precedes the structural and functional changes in corpora cavernosa (CC) leading to organic erectile dysfunction (ED). The present review gives an overview of the physiological factors involved in the regulation of penile vasculature. Sympathetic nerves maintain flaccidity and tonically released noradrenaline induces vasoconstriction of both arteries and veins through α1- and α2-postsynaptic receptors and downregulates its own release and that of nitric oxide (NO) through α2-presynaptic receptors. The sympathetic cotransmitter neuropeptide Y (NPY) modulates noradrenergic vasoconstriction in penile small arteries by both enhancing and depressing noradrenaline contractions through Y1- and Y2-postsynaptic and a NO-independent atypical endothelial receptor, respectively. Activation of α1-adrenoceptors involves both Ca2+ influx through L-type and receptor-operated Ca2+ channels (ROC) and Ca2+ sensitization mechanisms mediated by protein kinase C (PKC), tyrosine kinases (TKs) and Rho kinase (RhoK). In addition, RhoK can regulate Ca2+ entry in penile arteries upon receptor stimulation. Vasodilatation of penile arteries and large veins during erection is mediated by neurally released NO. The subsequent increased arterial inflow to the cavernosal sinoids and shear stress on the endothelium lining penile arteries activates endothelial NO production through Akt phosphorylation of endothelial NO synthase (eNOS). NO stimulates guanylate cyclase and increased cyclic guanin 3′-monophosphate (cGMP) levels in turn activate protein kinase G (PKG), which enhances K+ efflux through Ca2+-activated (KCa) and voltage-dependent Ca2+ (Kv) channels in penile arteries and veins, respectively. PKG-mediated decrease in Ca2+ sensitivity and its regulation by RhoK remains to be clarified in penile vasculature. Phosphodiesterase type 5 (PDE5) inhibitors are potent vasodilators of penile resistance arteries and increase the content and effects of basally released endothelial NO. Endothelium-dependent relaxations of penile small arteries also include an endothelium-derived hyperpolarizing factor (EDHF)-type response, which is impaired in diabetes and hypertension-associated ED. Locally produced contractile and relaxant prostanoids regulate penile venous and arterial tone, respectively. The latter activates prostaglandin I (IP) and prostaglandin E (EP) receptors coupled to adenylate cyclase and to the increase of cyclic adenosine monophosphate (cAMP) levels, which in turn stimulates K+ efflux through ATP-sensitive K+ (KATP) channels. There is a crosstalk between the cGMP and cAMP signaling pathways in penile small arteries. Relevant issues such as the mechanisms underlying the excitation–secretion coupling of the endothelial cells, as well as those involved in cell proliferation and vascular remodeling of the penile vasculature remain to be elucidated. In addition, only few studies have investigated the changes in structure and function of penile arteries in cardiovascular risk situations leading to ED.

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Acknowledgements

Dolores Prieto was supported by Grants no. PR1/06-14441-A from the Universidad Complutense de Madrid and Grant no. SAF2006-09191 from the Ministerio de Educación y Ciencia (España).

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Prieto, D. Physiological regulation of penile arteries and veins. Int J Impot Res 20, 17–29 (2008). https://doi.org/10.1038/sj.ijir.3901581

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  • DOI: https://doi.org/10.1038/sj.ijir.3901581

Keywords

  • penile arteries
  • calcium signalling
  • endothelial junction
  • nitric oxide
  • Rho kinase
  • erectile dysfunction

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