PMID- 15638909
OWN - NLM
STAT- MEDLINE
DCOM- 20050210
LR  - 20220321
IS  - 1464-4096 (Print)
IS  - 1464-4096 (Linking)
VI  - 95
IP  - 1
DP  - 2005 Jan
TI  - Cavernosal dysfunction in a rabbit model of hyperhomocysteinaemia.
PG  - 125-30
AB  - OBJECTIVE: To investigate the effect of sustained hyperhomocysteinaemia (HHCy) on 
      cavernosal smooth muscle function in a rabbit model of HHCy, developed using a 
      methionine-enriched diet in which cavernosal responses were characterized, as 
      elevated plasma levels of homocysteine may be a risk factor for vasculogenic 
      erectile dysfunction. MATERIALS AND METHODS: Six New Zealand White rabbits were 
      fed a diet supplemented with methionine (20 g/kg chow) for 4 weeks, while six 
      control animals were fed a standard diet. Cavernosal strips were mounted in an 
      organ bath and relaxation assessed when stimulated with carbachol, sodium 
      nitroprusside (SNP), or noncholinergic, nonadrenergic (NANC)-mediated relaxation 
      to electrical-field stimulation (EFS). Cavernosal tissue cGMP levels were 
      assessed using an enzyme-linked immunosorbent assay, and superoxide (O(2) (.-)) 
      production assessed using an assay of the superoxide dismutase (SOD)-inhibitable 
      reduction of ferricytochrome c. RESULTS: The methionine-rich diet led to an early 
      but sustained HHCy; cavernosal strips from animals after 4 weeks of HHCy had a 
      significantly impaired relaxation response to carbachol, an index of 
      endothelium-dependent nitric oxide (NO)-mediated relaxation. This impairment was 
      reversed by incubating with either SOD or catalase. Relaxation with either SNP, 
      an index of endothelium-independent NO-mediated relaxation, or NANC-mediated 
      EFS-induced relaxation, was unaffected by HHCy. There was a corresponding 
      significant reduction in cavernosal cGMP levels (index of NO activity) in the 
      HHCy group, with a more than five-fold increase in cavernosal tissue O(2) (.-) 
      production. CONCLUSION: Supplementing the diet of rabbits with methionine for 4 
      weeks caused an early and sustained HHCy and promoted a marked inhibitory effect 
      on endothelium-dependent relaxation and NO formation in isolated corpus 
      cavernosum, an effect mediated by reactive oxygen species.
FAU - Jones, Robert W A
AU  - Jones RW
AD  - Bristol Heart Institute, Royal Infirmary, University of Bristol, Bristol BS2 8HW, 
      UK.
FAU - Jeremy, Jamie Y
AU  - Jeremy JY
FAU - Koupparis, Anthony
AU  - Koupparis A
FAU - Persad, Raj
AU  - Persad R
FAU - Shukla, Nilima
AU  - Shukla N
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - BJU Int
JT  - BJU international
JID - 100886721
RN  - 0 (Vasoconstrictor Agents)
RN  - 11062-77-4 (Superoxides)
RN  - 1WS297W6MV (Phenylephrine)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - H2D2X058MU (Cyclic GMP)
SB  - IM
MH  - Animals
MH  - Cyclic GMP/metabolism
MH  - Hyperhomocysteinemia/*complications/physiopathology
MH  - Impotence, Vasculogenic/*etiology/physiopathology
MH  - Male
MH  - Muscle Relaxation/drug effects
MH  - Muscle, Smooth/*physiology
MH  - Nitric Oxide/metabolism
MH  - Penis/*physiology
MH  - Phenylephrine/pharmacology
MH  - Rabbits
MH  - Superoxides/metabolism
MH  - Vasoconstrictor Agents/pharmacology
EDAT- 2005/01/11 09:00
MHDA- 2005/02/11 09:00
CRDT- 2005/01/11 09:00
PHST- 2005/01/11 09:00 [pubmed]
PHST- 2005/02/11 09:00 [medline]
PHST- 2005/01/11 09:00 [entrez]
AID - BJU5263 [pii]
AID - 10.1111/j.1464-410X.2004.05263.x [doi]
PST - ppublish
SO  - BJU Int. 2005 Jan;95(1):125-30. doi: 10.1111/j.1464-410X.2004.05263.x.