Effects of losartan, HO-1 inducers or HO-1 inhibitors on erectile signaling in diabetic rats.
BACKGROUND
Activation of the renin-angiotensin system which is common in diabetes mellitus might affect heme oxygenase (HO-1) gene expression.


OBJECTIVE
Assessment of the effects of administration of angiotensin II (Ang II) receptor antagonist (losartan) with HO-1 inducer or inhibitor on erectile signaling in diabetic rats.


METHODS
Seventy male rats were divided equally into seven groups; healthy controls, streptozotocin-induced diabetic rats, rats on citrate buffer, diabetic rats on losartan, diabetic rats on HO-1 inducer (cobalt protoporphyrin [CoPP]), diabetic rats on losartan and CoPP, and diabetic rats on losartan and HO-1 inhibitor (stannus mesoporphyrin [SnMP]).


METHODS
HO enzyme activity, HO-1 gene expression, cyclic guanosine monophosphate (cGMP) assay, intracavernosal pressure (ICP), and cavernous tissue sinusoids surface area.


RESULTS
HO-1 gene expression, HO enzymatic activity, and cGMP were significantly decreased in the cavernous tissue of diabetic rats. These parameters were significantly elevated with the use of CoPP that restored the normal control levels of HO enzyme activity. Administration of losartan exhibited a significant enhancing effect on these parameters compared with the diabetic group, but not restored to the control levels, whereas administration of CoPP combined with losartan led to the restoration of their normal levels. ICP demonstrated significant decline in diabetic rats. The use of CoPP and/or losartan led to its significant improvement compared with diabetic rats. Administration of either losartan and/or CoPP led to a significant increase in the cavernous sinusoids surface area of diabetic rats. Administration of losartan with SnMP significantly decreased the enhancing effect of losartan on the studied parameters.


CONCLUSIONS
The decline in erectile function in diabetes mellitus could be attributed to the downregulation of HO-1 gene expression. HO-1 induction added to Ang II receptor antagonist could improve erectile function.
Abdel Aziz
Mohamed Talaat
MT
Faculty of Medicine, Cairo University, Medical Biochemistry, Unit of Biochemistry & Molecular Biology, Cairo, Egypt.
El Asmer
Mohamed Farid
MF
Mostafa
Taymour
T
Atta
Hazem
H
Mahfouz
Soheir
S
Fouad
Hanan
H
Rashed
Laila
L
Sabry
Dina
D
Hassouna
Amira
A
Abdel Aziz
Ahmed Talaat
AT
Senbel
Amira
A
Demery
Ahmed
A
D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002352:Carrier Proteins; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D004195:Disease Models, Animal; D007172:Erectile Dysfunction / Q000175:diagnosis* / Q000209:etiology / Q000503:physiopathology; D015870:Gene Expression; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins; D019808:Losartan / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D010410:Penile Erection / Q000187:drug effects*; D012313:RNA / Q000235:genetics; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016896:Treatment Outcome
D000959:Antihypertensive Agents; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; C022994:cyclic GMP-binding protein; D012313:RNA; D051547:Heme Oxygenase-1; D019808:Losartan