PMID- 15127883
OWN - NLM
STAT- MEDLINE
DCOM- 20040625
LR  - 20191026
IS  - 0916-9636 (Print)
IS  - 0916-9636 (Linking)
VI  - 27
IP  - 4
DP  - 2004 Apr
TI  - Erectile dysfunction in hypertensive rats results from impairment of the 
      relaxation evoked by neurogenic carbon monoxide and nitric oxide.
PG  - 253-61
AB  - 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.
FAU - Ushiyama, Masayuki
AU  - Ushiyama M
AD  - Fourth Department of Internal Medicine, Saitama Medical School, Saitama, Japan.
FAU - Morita, Toshisuke
AU  - Morita T
FAU - Kuramochi, Tomoya
AU  - Kuramochi T
FAU - Yagi, Shinji
AU  - Yagi S
FAU - Katayama, Shigehiro
AU  - Katayama S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Hypertens Res
JT  - Hypertension research : official journal of the Japanese Society of Hypertension
JID - 9307690
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Protoporphyrins)
RN  - 15442-64-5 (zinc protoporphyrin)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 7U1EE4V452 (Carbon Monoxide)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type I)
RN  - EC 1.14.13.39 (Nos1 protein, rat)
RN  - EC 1.14.14.18 (Heme Oxygenase (Decyclizing))
RN  - EC 1.14.14.18 (heme oxygenase-2)
RN  - H2D2X058MU (Cyclic GMP)
SB  - IM
MH  - Animals
MH  - Carbon Monoxide/*metabolism
MH  - Cyclic GMP/metabolism
MH  - Enzyme Inhibitors/pharmacology
MH  - Erectile Dysfunction/*etiology/*metabolism/physiopathology
MH  - Gene Expression Regulation, Enzymologic
MH  - Heme Oxygenase (Decyclizing)/antagonists & inhibitors/genetics
MH  - Hypertension/*complications/*metabolism/physiopathology
MH  - Male
MH  - Neurons/metabolism
MH  - Nitric Oxide/*metabolism
MH  - Nitric Oxide Synthase/genetics
MH  - Nitric Oxide Synthase Type I
MH  - Oxidative Stress
MH  - Penile Erection/drug effects/physiology
MH  - Penis/blood supply/innervation/physiopathology
MH  - Protoporphyrins/pharmacology
MH  - Rats
MH  - Rats, Inbred SHR
MH  - Rats, Inbred WKY
MH  - Vasodilation
EDAT- 2004/05/07 05:00
MHDA- 2004/06/26 05:00
CRDT- 2004/05/07 05:00
PHST- 2004/05/07 05:00 [pubmed]
PHST- 2004/06/26 05:00 [medline]
PHST- 2004/05/07 05:00 [entrez]
AID - 10.1291/hypres.27.253 [doi]
PST - ppublish
SO  - Hypertens Res. 2004 Apr;27(4):253-61. doi: 10.1291/hypres.27.253.