Probing Erectile Function: S-(2-Boronoethyl)-l-Cysteine Binds to Arginase as a Transition State Analogue and Enhances Smooth Muscle Relaxation in Human Penile Corpus Cavernosum†,‡

Biochemistry ◽  
2001 ◽  
Vol 40 (9) ◽  
pp. 2678-2688 ◽  
Author(s):  
Noel N. Kim ◽  
J. David Cox ◽  
Ricky F. Baggio ◽  
Frances A. Emig ◽  
Sanjay K. Mistry ◽  
...  
2001 ◽  
Vol 281 (2) ◽  
pp. R476-R483 ◽  
Author(s):  
T. M. Mills ◽  
D. M. Pollock ◽  
R. W. Lewis ◽  
H. S. Branam ◽  
C. J. Wingard

Recent evidence indicates that endothelin-1 (ET-1) might be a principal vasoconstrictor in the penis. We report that ET-1 injection into the cavernous sinuses before erection sharply reduced the magnitude of subsequent erections. Corpus cavernosum pressure-to-mean arterial pressure ratios (CCP/MAP), with maximal ganglionic stimulation, were 0.62 ± 0.05 before ET-1 injection and 0.31 ± 0.05 after, indicating that ET-1 acted as a vasoconstrictor. When ET-1 was injected during a maximal neurally induced erection, the ability of ET-1 to attenuate subsequent erections was diminished (CCP/MAP 0.75 ± 0.02 before ET-1, 0.61 ± 0.03 after). At submaximal stimulation voltages, injection of ET-1 during erection also attenuated its vasoconstrictive effect. Similarly, when ET-1 was injected during erection induced by intracavernosal injection of the nitric oxide (NO) donor NOR-1, subsequent erections were not significantly suppressed (CCP/MAP 0.53 ± 0.04 before ET-1, 0.45 ± 0.04 after). These findings that ET-1-induced vasoconstriction is attenuated during erection are consistent with the hypothesis that NO mediates erection both by initiating pathways that cause smooth muscle relaxation and by inhibiting the vasoconstrictive actions of ET-1.


2016 ◽  
Vol 195 (4S) ◽  
Author(s):  
Faysal A Yafi ◽  
Serap Gur ◽  
Taylor Peak ◽  
Philip J Kadowitz ◽  
Suresh C Sikka ◽  
...  

Life Sciences ◽  
1998 ◽  
Vol 63 (3) ◽  
pp. 185-194 ◽  
Author(s):  
Alex T. Chuang ◽  
John D. Strauss ◽  
William D. Steers ◽  
Richard A. Murphy

2006 ◽  
Vol 290 (5) ◽  
pp. R1302-R1308 ◽  
Author(s):  
A. Elizabeth Linder ◽  
Romulo Leite ◽  
Kimberly Lauria ◽  
Thomas M. Mills ◽  
R. Clinton Webb

Erectile dysfunction is caused by a variety of pathogenic factors, particularly impaired formation and action of nitric oxide (NO). NO released from nerve endings and corpus cavernosum endothelial cells plays a crucial role in initiating and maintaining increased intracavernous pressure, penile vasodilatation, and penile erection. Classically, these effects are dependent on cGMP synthesized during activation of soluble guanylyl cyclase (sGC) by NO in smooth muscle cells. The enzyme NO synthase in endothelial cells has been localized to caveolae, small invaginations of the plasma membrane rich in cholesterol. Membrane cholesterol depletion impairs acetylcholine-induced relaxation in arteries attributed to an alteration in caveolar structure. It has been shown that sGC may be activated in endothelial caveolae contributing to vasodilation. We hypothesized that caveolae are the platform for sGC/cGMP signaling in cavernosum smooth muscle eliciting erection. Methyl-β-cyclodextrin, a pharmacological tool to deplete membrane cholesterol and disassemble caveolae, impaired rat erectile responses in vivo and cavernosum smooth muscle relaxation induced by the NO donor sodium nitroprusside and the sGC activator 3-(5′-hydroxymethyl-2′-furyl)-1-benzyl indazole in vitro. Methyl-β-cyclodextrin had no effect on cavernosum smooth muscle relaxation induced by NO released upon nerve stimulation or by exogenous cGMP. Furthermore, sGC and caveolin-1, the major coat protein of caveolae, were colocalized in rat corpus cavernosum sinusoidal endothelium. Electron microscopy indicated caveolae disruption in corpus cavernosum treated with methyl-β-cyclodextrin. In summary, our results provide evidence of compartmentalization of sGC in the caveolae of cavernosal endothelial cells contributing to NO signaling mediating smooth muscle relaxation and erection.


2008 ◽  
Vol 14 (S3) ◽  
pp. 152-155 ◽  
Author(s):  
N. Tomada ◽  
R. Oliveira ◽  
I. Tomada ◽  
P. Vendeira ◽  
D. Neves

Erectile Dysfunction (ED), the inability to achieve or maintain an erection of sufficient rigidity for completion of sexual act, is a common condition affecting more than 150 million of men worldwide. This disorder is highly associated with aging, however concomitant pathologies such as hyperlipidemia, hypertension, and diabetes also contribute to ED progression. In the Massachusetts Male Aging Study, age was considered an independent variable strongly associated with ED, showing that the prevalence of this disease increased with age from 38% in the youngest group of men (mean age 40 y.) to almost 70% in the oldest group of men examined (mean age 70 y.). It is well demonstrated that aging leads to changes in the cardiovascular system, which results in a decrease in elasticity due to fibrosis and an increase in stiffness of the arterial system, independently of the effects of concurrent pathologies. Vasculogenic ED is the most prevalent condition, affecting nearly 80% of patients with organic etiology. Small vessels of the penis are very sensitive to structural and functional changes, and small disturbances can conduce to ED. ED is now considered by some authors as synonymous to endothelial dysfunction and an early manifestation of atherosclerosis, being a precursor of systemic vascular disease. Human cavernous tissue is mainly constituted by smooth muscle fibers that surround sinusoid vessels. Corpus cavernosum structural elements act in concert, allowing increase of intra-cavernous arterial flow and smooth muscle relaxation processes which are fundamental to penile erection. The aim of this study was to compare the ultrastructural anatomy of the young and aged human corpus cavernosum, in the absence of additional risk factors.


2010 ◽  
Vol 36 (4) ◽  
pp. 490-496 ◽  
Author(s):  
Rommel P. Regadas ◽  
Maria E. A. Moraes ◽  
Francisco J. C. Mesquita ◽  
Joao B. G. Cerqueira ◽  
Lucio F. Gonzaga-Silva

1993 ◽  
Vol 150 (1) ◽  
pp. 249-252 ◽  
Author(s):  
William W. Kerfoot ◽  
Hae Young Park ◽  
Lewis B. Schwartz ◽  
Per-otto Hagen ◽  
Culley C. Carson

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