More than 50 percent of patients with diabetes have erectile dysfunction, with autonomic neuropathy playing a proximal role. However, the precise contribution of autonomic neuropathy to diabetic erectile dysfunction remains undefined. Part of the difficulty in establishing the etiologic role of the autonomic nervous system in diabetic erectile dysfunction is related to the fact that the penis is endowed with multiple mechanisms for preserving syncytial tissue function. In particular, the interaction among: 1. neuronal innervation, 2. cell-to-cell communication, and 3. myogenic intracellular signal transduction processes, are critical to guarantee erectile function over a wide range of physiological conditions. Such plasticity is expected of an organ critical to the survival of the species and the physiological well being of men and their sexual partners. The explicit aim of these studies is to utilize an established rat model of experimental diabetic neuropathy to evaluate the effects of diabetes on autonomic innervation in the penis, and any correlative changes that occur in intercellular communication and myogenic responsivity. In particular, we will test the hypothesis that autonomic neuropathy is associated with global alterations in tissue function, that result, at least in part, from alterations in ion flow through potassium (K) and gap junction channels. Specifically, we shall induce a 1-6 month period of streptozotocin (STZ)-diabetes in Fischer-344 (F-344) rats, and: 1. Evaluate the functional correlates of molecular changes in K channels and gap junctions that are associated with experimental diabetic neuropathy/hyperglycemia, and 2. To evaluate the functional correlates of the molecular changes in K channels and gap junctions that are produced by a novel gene therapy approach for the amelioration of erectile dysfunction. To this end, we will utilize techniques ranging from in vivo animal studies, through in vitro studies at the tissue, cellular, subcellular and molecular/genetic levels. By bringing to bear such a diverse array of techniques on this important medical problem we hope to gain the greatest insight possible into the functional correlates in vivo of well quantified molecular alterations.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK055076-03
Application #
6626972
Study Section
Special Emphasis Panel (ZRG1-UROL (01))
Program Officer
Rankin, Tracy L
Project Start
2001-03-01
Project End
2003-12-31
Budget Start
2003-01-01
Budget End
2003-12-31
Support Year
3
Fiscal Year
2003
Total Cost
$417,500
Indirect Cost
Name
Albert Einstein College of Medicine
Department
Urology
Type
Schools of Medicine
DUNS #
071036636
City
Bronx
State
NY
Country
United States
Zip Code
10461
Yoshimura, Naoki; Chancellor, Michael B; Andersson, Karl-Erik et al. (2005) Recent advances in understanding the biology of diabetes-associated bladder complications and novel therapy. BJU Int 95:733-8
Christ, George J; Liebert, Monica (2005) Proceedings of the Baltimore smooth muscle meeting: identifying research frontiers and priorities for the lower urinary tract. J Urol 173:1406-9
Christ, George J; Day, Nancy; Santizo, Cristian et al. (2004) Intracorporal injection of hSlo cDNA restores erectile capacity in STZ-diabetic F-344 rats in vivo. Am J Physiol Heart Circ Physiol 287:H1544-53
Christ, George J (2002) K channels as molecular targets for the treatment of erectile dysfunction. J Androl 23:S10-9