Corpus cavernosum dysfunction in diabetic rats: effects of combined alpha-lipoic acid and gamma-linolenic acid treatment.
BACKGROUND
The effects of streptozotocin-induced diabetes on nitric oxide (NO)-mediated relaxation of rat corpus cavernosum smooth muscle to neurogenic and endothelial stimulation was examined. The aim was to assess the effects of treatment with low doses of the antioxidant, alpha-lipoic acid, and the omega-6 essential fatty acid, gamma-linolenic acid, either separately or in combination.


METHODS
Treatment was preventive from diabetes induction or corrective over 4 weeks after 4 weeks of untreated diabetes. Corpus cavernosum responses were examined in vitro.


RESULTS
Neither diabetes nor treatment affected contractile responses to transmural electrical field stimulation of noradrenergic nerves. Stimulation of phenylephrine precontracted cavernosa in the presence of guanethidine and atropine caused relaxation via the nitrergic innervation. Maximum relaxation responses were 40% and 46% decreased after 4 and 8 weeks of diabetes, respectively. alpha-Lipoic acid, gamma-linolenic acid combination treatment fully prevented this deficit, and partially (52%) corrected the effect of 4 weeks of untreated diabetes. Neither alpha-lipoic acid nor gamma-linolenic components alone had significant effects, which suggests that there were synergistic interactions between the drugs. Both 4 and 8 weeks of untreated diabetes reduced maximum endothelium-dependent relaxation of phenylephrine precontracted cavernosa to acetylcholine by approximately 40%. While alpha-lipoic acid or gamma-linolenic acid were ineffective, joint treatment fully prevented and corrected this diabetic endothelial deficit. Neither diabetes nor treatment affected endothelium-independent relaxation to the NO donor, sodium nitroprusside.


CONCLUSIONS
The data show that alpha-lipoic acid and gamma-linolenic acid interact synergistically to improve NO-mediated neurogenic and endothelium-dependent relaxation of corpus cavernosum in experimental diabetes.
Keegan
A
A
Department of Biomedical Sciences, University of Aberdeen, Aberdeen, Scotland, UK.
Cotter
M A
MA
Cameron
N E
NE
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001786:Blood Glucose / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D004359:Drug Therapy, Combination; D004558:Electric Stimulation; D007172:Erectile Dysfunction / Q000188:drug therapy* / Q000209:etiology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000098:blood supply / Q000294:innervation / Q000503:physiopathology; D009569:Nitric Oxide / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019335:Nitroarginine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010413:Penis / Q000098:blood supply / Q000294:innervation; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D008063:Thioctic Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D017965:gamma-Linolenic Acid / Q000008:administration & dosage / Q000627:therapeutic use*
D000975:Antioxidants; D001786:Blood Glucose; D020030:Nitric Oxide Donors; D009599:Nitroprusside; D010656:Phenylephrine; D019335:Nitroarginine; D009569:Nitric Oxide; D008063:Thioctic Acid; D017965:gamma-Linolenic Acid; D000109:Acetylcholine