Enzyme activities of the nitric oxide-cGMP pathway in corpus cavernosum isolated from middle-aged rats.
Cyclic guanosine-3',5'-monophosphate (cGMP)-mediated mechanisms play an important role in vasodilation and blood pressure regulation. We investigated basal activity of the nitric oxide (NO)-cGMP signal transduction pathway in corpus cavernosum from both middle-aged and young rats, and the electrical field stimulation-induced relaxation in the organ was also evaluated. In middle-aged rats, nitric oxide synthase (NOS) and cGMP-phosphodiesterase activities were significantly decreased; however, guanylate cyclase activity was similar. cGMP concentration, a secondary messenger of NO, remained almost the same level as compared with young rats. These results suggest that decrease in cGMP-phosphodiesterase activity is likely to account for the maintenance of cGMP concentration. In isolated corpus cavernosum from middle-aged rats, electrical field stimulation-induced relaxation was partially impaired. These results suggest that downregulation of the NOS and cGMP-phosphodiesterase activities are early events in the pathogenesis of erectile dysfunction.
Hosogai
Naomi
N
Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., 2-1-6, Kashima, Yodogawa-ku, Osaka 532-8514, Japan. naomi_hosogai@po.fujisawa.co.jp
Takakura
Shoji
S
Manda
Toshitaka
T
Mutoh
Seitaro
S
D018663:Adrenergic Agents / Q000494:pharmacology; D000367:Age Factors; D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism*; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000378:metabolism; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects / Q000502:physiology; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000201:enzymology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010413:Penis / Q000187:drug effects* / Q000201:enzymology*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D000071756:Soluble Guanylyl Cyclase
D018663:Adrenergic Agents; D004791:Enzyme Inhibitors; D018160:Receptors, Cytoplasmic and Nuclear; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D010727:Phosphoric Diester Hydrolases; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; D006152:Cyclic GMP