Chronic alcoholism associated with diabetes impairs erectile function in rats.
OBJECTIVE
To investigate the effects of chronic ethanol consumption and diabetes on nitric oxide (NO)-mediated relaxation of cavernosal smooth muscle (CSM).


METHODS
Male Wistar rats were divided into four groups: control, isocaloric, diabetic and ethanol-diabetic. The CSMs were mounted in organ chambers for measurement of isometric tension. Contraction of the strips was induced by electrical field stimulation (EFS, 1-32 Hz) and phenylephrine. We also evaluated the effect of ethanol consumption on the relaxation induced by acetylcholine (ACh; 0.01-1000 micromol/L), sodium nitroprusside (SNP, 0.01-1000 micromol/L) or EFS (1-32 Hz) in strips pre-contracted with phenylephrine (10 micromol/L). Immunoexpression of endothelial NO synthase (eNOS) and inducible NOS (iNOS) was also accessed.


RESULTS
The endothelium-dependent relaxation induced by ACh was decreased in CSM from ethanol-diabetic rats when compared with the controls, with a mean (sem) of 21 (4) vs 37 (2)%. Similarly, the potency and maximal responses induced by SNP were reduced in the ethanol-diabetic [3.97 (0.38) and 85 (1)%, respectively] and diabetic groups [3.78 (0.56) and 81 (2)%, respectively] when compared with the controls [5.3 (0.22) and 90 (3)%, respectively] and isocaloric [5.3 (0.19) and 92 (1)%, respectively] groups. Noradrenergic nerve-mediated contractions of CSM in response to EFS were increased in rats from ethanol-diabetic and diabetic groups when compared with the control and isocaloric groups. Conversely, there were no differences in EFS-induced relaxation among the groups. The immunostaining assays showed overexpression of eNOS and iNOS in the CSM from diabetic and ethanol-diabetic rats when compared with the control and isocaloric rats.


CONCLUSIONS
There was an impairment of relaxation of CSM from ethanol-diabetic and diabetic rats that involved a decrease in the NO-cyclic guanosine monophosphate signalling pathway by endothelium-dependent mechanisms accompanied by a change in the CSM contractile sensitivity.
Lizarte
Fermino S
FS
Department of Psychiatric Nursing and Human Sciences, Laboratory of Pharmacology, College of Nursing of Ribeirão Preto, University of São Paulo (USP), Brazil.
Morgueti
Marcelo
M
Tirapelli
Carlos R
CR
Claudino
Mario A
MA
Evora
Paulo R B
PR
Novais
Paulo C
PC
Tirapelli
Daniela P C
DP
Celotto
Andrea C
AC
Capellini
Verena K
VK
Celini
Fabia P M
FP
Tucci
Silvio
S
Cologna
Adauto J
AJ
Antunes
Edson
E
Martins
Antonio C P
AC
Tirapelli
Luis F
LF
D000437:Alcoholism / Q000150:complications*; D000818:Animals; D048909:Diabetes Complications / Q000150:complications*; D007172:Erectile Dysfunction / Q000209:etiology*; D007150:Immunohistochemistry; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009599:Nitroprusside / Q000494:pharmacology; D010413:Penis / Q000187:drug effects*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D010656:Phenylephrine