Impotence is a common disorder, which affects an estimated 10 million American men. In many people impotence has a profound effect on their well-being. Considerable advances have been made in the understanding of the physiology and pathophysiology of erectile function, however, many important questions remain unanswered. What is the role of the endothelium in penile erection? To what extent does the endothelium-dependent relaxation contribute to the initiation and maintenance of penile erection? How do alterations in endothelial function caused by disease states affect penile erectile function? Does the endothelium participate in the maintenance of smooth muscle resting tone and, therefore, in maintaining penile flaccidity? How do hypoxia and acidosis, which occur in veno-occlusive priapism, affect corporal smooth muscle contractility and perpetuate the priapistic erection? The general aim of this grant continues to be the study of the role of the corpus cavernosum vascular endothelium in the physiology and pathophysiology of penile erectile function. The present proposal will also focus on the pathophysiology of priapism and how the associated hypoxia and acidosis impair the normal reactivity of corporal smooth muscle and cause injury to the erectile tissue that can lead to erectile dysfunction. Human and rabbit corpus cavernosum tissue and cultured endothelial cells derived from these tissues will be used in these studies. The following specific aims are proposed: 1) To determine the balance between eicosanoids and nitric oxide in the modulation of corpus cavernosum smooth muscle tone. 2) To determine the effects of hypoxia and acidosis on the contractility of corpus cavernosum smooth muscle. 3) To determine the relationship between endothelium, membrane potential, ionic fluxes, and corpus cavernosum smooth muscle contractility. Alterations by hypoxia and acidosis. 4) To determine if an increase in adenosine production during hypoxia causes depression of corporal smooth muscle contractility.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK040487-08
Application #
2141349
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1988-08-01
Project End
1996-07-31
Budget Start
1995-08-15
Budget End
1996-07-31
Support Year
8
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Boston University
Department
Urology
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118
Udelson, D; L'Esperance, J; Morales, A M et al. (2000) The mechanics of corporal veno-occlusion in penile erection: a theory on the effect of stretch-associated luminal constrictability on outflow resistance. Int J Impot Res 12:315-27
Traish, A; Moreland, R B; Huang, Y H et al. (1999) Development of human and rabbit vaginal smooth muscle cell cultures: effects of vasoactive agents on intracellular levels of cyclic nucleotides. Mol Cell Biol Res Commun 2:131-7
Moreland, R B; Goldstein, I; Traish, A (1998) Sildenafil, a novel inhibitor of phosphodiesterase type 5 in human corpus cavernosum smooth muscle cells. Life Sci 62:PL 309-18
Udelson, D; Nehra, A; Hatzichristou, D G et al. (1998) Engineering analysis of penile hemodynamic and structural-dynamic relationships: Part I--Clinical implications of penile tissue mechanical properties. Int J Impot Res 10:15-24
Udelson, D; Nehra, A; Hatzichristou, D G et al. (1998) Engineering analysis of penile hemodynamic and structural-dynamic relationships: Part II--Clinical implications of penile buckling. Int J Impot Res 10:25-35
Udelson, D; Nehra, A; Hatzichristou, D G et al. (1998) Engineering analysis of penile hemodynamic and structural-dynamic relationships: Part III--Clinical considerations of penile hemodynamic and rigidity erectile responses. Int J Impot Res 10:89-99
Gupta, S; Moreland, R B; Yang, S et al. (1998) The expression of functional postsynaptic alpha2-adrenoceptors in the corpus cavernosum smooth muscle. Br J Pharmacol 123:1237-45
Gupta, S; Salimpour, P; Saenz de Tejada, I et al. (1998) A possible mechanism for alteration of human erectile function by digoxin: inhibition of corpus cavernosum sodium/potassium adenosine triphosphatase activity. J Urol 159:1529-36
Park, K; Moreland, R B; Goldstein, I et al. (1998) Sildenafil inhibits phosphodiesterase type 5 in human clitoral corpus cavernosum smooth muscle. Biochem Biophys Res Commun 249:612-7
Mulhall, J P; Daller, M; Traish, A M et al. (1997) Intracavernosal forskolin: role in management of vasculogenic impotence resistant to standard 3-agent pharmacotherapy. J Urol 158:1752-8; discussion 1758-9

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