Erectile dysfunction in hypertensive rats results from impairment of the relaxation evoked by neurogenic carbon monoxide and nitric oxide.
Erectile dysfunction (ED) with aging and diabetes mellitus is caused by impairment of the relaxation evoked by nitric oxide (NO) of penile cavernous smooth muscles and arterioles. However, the mechanism of ED in hypertension is unknown. Carbon monoxide (CO), which is produced by heme oxygenase (HO)-2 in the neuronal system is a neurotransmitter and a vasodilator. We examined the neurogenic role of CO in penile erection and the neurogenic mechanisms of ED in hypertension, using spontaneously hypertensive rats (SHR) or Wistar-Kyoto rats (WKY). The isometric tension of corpus cavernosum tissues from both strains was recorded after guanethidine and atropine treatment. Relaxation in response to electrical field stimulation (EFS) in WKY was suppressed dose-dependently by HO inhibitors both in the absence and presence of an NO synthase (NOS) inhibitor. Reverse transcription-polymerase chain reaction (RT-PCR) showed that the HO-2 gene was expressed in the corpus cavernosum. CO-saturated solution induced a concentration-dependent relaxation in WKY. The neurogenic relaxation to EFS in SHR was impaired as compared with that in WKY after the age of 5 weeks, when blood pressure began to be elevated, due to the attenuated relaxation in response to neurogenic NO and CO. In the corpus cavernosum of SHR, expression of the HO-2 and nNOS genes was similar, and NOx levels after EFS were similar to those of WKY. cGMP levels after EFS and the relaxation evoked by the NO donor was lower in SHR than WKY. Thiobarbituric acid-reacting substance (TBARS) levels were increased, and superoxide dismutase (SOD) activity was suppressed in SHR, as compared with those in WKY, suggesting that the increasing oxidative stress partially causes the impairment of NO-dependent relaxation. These findings suggest that CO regulates the relaxation evoked by EFS in the rat corpus cavernosum, and that ED in hypertension in rats results from an impairment of the relaxation induced by neurogenic CO and NO.
Ushiyama
Masayuki
M
Fourth Department of Internal Medicine, Saitama Medical School, Saitama, Japan.
Morita
Toshisuke
T
Kuramochi
Tomoya
T
Yagi
Shinji
S
Katayama
Shigehiro
S
D000818:Animals; D002248:Carbon Monoxide / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007172:Erectile Dysfunction / Q000209:etiology* / Q000378:metabolism* / Q000503:physiopathology; D015971:Gene Expression Regulation, Enzymologic; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors / Q000235:genetics; D006973:Hypertension / Q000150:complications* / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D009474:Neurons / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000235:genetics; D052248:Nitric Oxide Synthase Type I; D018384:Oxidative Stress; D010410:Penile Erection / Q000187:drug effects / Q000502:physiology; D010413:Penis / Q000098:blood supply / Q000294:innervation / Q000503:physiopathology; D011524:Protoporphyrins / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014664:Vasodilation
D004791:Enzyme Inhibitors; D011524:Protoporphyrins; C017803:zinc protoporphyrin; D009569:Nitric Oxide; D002248:Carbon Monoxide; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D006419:Heme Oxygenase (Decyclizing); C105245:heme oxygenase-2; D006152:Cyclic GMP