Enhanced relaxation of diabetic rabbit cavernosal smooth muscle in response to nitric oxide: potential relevance to erectile dysfunction.
New Zealand white rabbit cavernosal smooth muscle strips (n=6) were mounted in organ baths. Relaxations to nitric oxide (10(-7)-10(-4) mol/l) were measured and the same procedure was repeated on strips from rabbits 6 months after alloxan-induced diabetes (n=6). Transverse cavernosal sections were obtained from the same penises. Low and high resolution autoradiographs were prepared using [(3)H]-L-N(G)-nitroarginine (an index of nitric oxide binding sites) and analysed densitometrically. Histochemical analysis was performed on adjacent sections using NADPH diaphorase (an index of nitric oxide synthase activity). Nitric oxide relaxed control rabbit cavernosal smooth muscle strips in a concentration-dependent manner. Diabetic rabbit cavernosal smooth muscle strips were significantly (P<0.03) more sensitive to nitric oxide (mean IC(50)=3.9 x 10(-6) mol/l). Nitric oxide synthase binding sites were localised to the cavernosal endothelium and smooth muscle. Nitric oxide synthase activity was increased in 6 month diabetic cavernosal smooth muscle. These findings suggest impairments in the L-arginine-nitric oxide pathway may play a role in the pathophysiology of diabetic erectile dysfunction.
Sullivan
M E
ME
Department of Urology (Molecular Pathology), Royal Free and University College Medical School and The Royal Free Hampstead NHS Trust, Pond Street, London, UK. sullyme@hotmail.com
Mumtaz
F H
FH
Dashwood
M R
MR
Thompson
C S
CS
Naseem
K M
KM
Bruckdorfer
K R
KR
Mikhailidis
D P
DP
Morgan
R J
RJ
D000109:Acetylcholine / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D001665:Binding Sites; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D002784:Cholesterol / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D004558:Electric Stimulation; D007172:Erectile Dysfunction / Q000209:etiology; D006651:Histocytochemistry; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction; D009126:Muscle Relaxation; D009130:Muscle, Smooth / Q000187:drug effects* / Q000503:physiopathology; D009569:Nitric Oxide / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010413:Penis / Q000187:drug effects* / Q000503:physiopathology; D010656:Phenylephrine / Q000494:pharmacology; D011817:Rabbits; D014665:Vasodilator Agents / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D001786:Blood Glucose; D014665:Vasodilator Agents; D010656:Phenylephrine; D009569:Nitric Oxide; D002784:Cholesterol; D019001:Nitric Oxide Synthase; D000109:Acetylcholine