The effect of superoxide dismutase on nitric oxide-mediated and electrical field-stimulated diabetic rabbit cavernosal smooth muscle relaxation.
OBJECTIVE
To investigate the effect of superoxide dismutase (SOD, the enzyme that accelerates the breakdown of the superoxide anion, O2- to H2O) on nitric oxide (NO)-mediated and electrical field stimulated (EFS) relaxation in diabetic rabbit cavernosal smooth muscle. Materials and methods Diabetes was induced with alloxan (65 mg/kg) in six adult New Zealand White rabbits. After 6 months, cavernosal smooth muscle strips from age-matched controls and diabetic animals were mounted in organ baths. After precontraction with phenylephrine (10 micromol/L) in the presence of atropine (1 micromol/L), guanethidine (5 micromol/L) and indomethacin (10 micromol/L), relaxation responses to EFS (1-20 Hz), carbachol (10(-8)-10(-4) mol/L) and sodium nitroprusside (SNP, 10(-9)-10(-4) mol/L) were assessed in the presence and absence of SOD (100 IU/mL).


RESULTS
SNP- and carbachol-mediated (endothelium-independent and -dependent, respectively) relaxations were impaired in the diabetic cavernosal smooth muscle strips compared with controls (concentration required for 50% inhibition, 1.4 micromol/L for diabetic and 0.75 micromol/L for control with SNP, and 44 micromol/L for diabetic and 0.4 micromol/L for control with carbachol). SOD significantly enhanced both SNP- and carbachol-mediated diabetic cavernosal smooth muscle relaxations (both P < 0.05). EFS-mediated relaxations were also significantly (P < 0.05) impaired in the diabetic cavernosal smooth muscle strips; these relaxations were also significantly (P < 0.05) enhanced by SOD.


CONCLUSIONS
NO- and EFS-mediated cavernosal smooth muscle relaxation is impaired in a rabbit model of diabetes but SOD significantly reversed the impaired relaxation. Therefore, in diabetes, the generation of reactive oxygen species may play an important role in the development of erectile dysfunction.
Khan
M A
MA
Department of Urology, Royal Free and University College Medical School (University College London), Royal Free Campus & The Royal Free Hampstead NHS Trust, London, UK.
Thompson
C S
CS
Jeremy
J Y
JY
Mumtaz
F H
FH
Mikhailidis
P
P
Morgan
R J
RJ
D000496:Alloxan; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology / Q000503:physiopathology; D004558:Electric Stimulation; D007172:Erectile Dysfunction / Q000201:enzymology; D008297:Male; D009126:Muscle Relaxation / Q000502:physiology*; D009130:Muscle, Smooth / Q000201:enzymology*; D009569:Nitric Oxide / Q000502:physiology*; D010413:Penis / Q000201:enzymology / Q000502:physiology*; D011817:Rabbits; D013482:Superoxide Dismutase / Q000494:pharmacology*
D009569:Nitric Oxide; D000496:Alloxan; D013482:Superoxide Dismutase