Losartan, an Angiotensin type I receptor, restores erectile function by downregulation of cavernous renin-angiotensin system in streptozocin-induced diabetic rats.
BACKGROUND
The high incidence of erectile dysfunction (ED) in diabetes highlights the need for good treatment strategies. Recent evidence indicates that blockade of the angiotensin type I receptor (AT1) may reverse ED from various diseases.


OBJECTIVE
To explore the role of cavernous renin-angiotensin system (RAS) in the pathogenesis of diabetic ED and the role of losartan in the treatment of diabetic ED.


METHODS
The AT1 blocker (ARB) losartan (30 mg/kg/d) was administered to rats with streptozocin (65 mg/kg)-induced diabetes. Erectile function, cavernous structure, and tissue gene and protein expression of RAS in the corpora cavernosa were studied.


METHODS
We sought to determine the changes of cavernous RAS in the condition of diabetes and after treatment with losartan.


RESULTS
RAS components (angiotensinogen, [pro]renin receptor, angiotensin-converting enzyme [ACE], and AT1) were expressed in cavernosal tissue. In diabetic rats, RAS components were upregulated, resulting in the increased concentration of angiotensin II (Ang II) in the corpora. A positive feedback loop for Ang II formation in cavernosum was also identified, which could contribute to overactivity of cavernous RAS in diabetic rats. Administration of losartan blocked the effect of Ang II, downregulated the expression of AT1 and Ang II generated locally, and partially restored erectile function (losartan-treated group revealed an improved intracavernous pressure/mean systemic arterial pressure ratio as compared with the diabetic group (0.480 +/- 0.031 vs. 0.329 +/- 0.020, P < 0.01). However, losartan could not elevate the reduced smooth muscle/collagen ratio in diabetic rats.


CONCLUSIONS
The cavernous RAS plays a role in modulating erectile function in corpora cavernosa and is involved in the pathogenesis of diabetic ED. ARB can restore diabetic ED through downregulating cavernous RAS.
Yang
Rong
R
Affiliated Drum Tower Hospital of Nanjing University, School of Medicine-Urology, Nanjing, China.
Yang
Bin
B
Wen
Yanting
Y
Fang
Feng
F
Cui
Souxi
S
Lin
Guiting
G
Sun
Zeyu
Z
Wang
Run
R
Dai
Yutian
Y
D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000818:Animals; D015153:Blotting, Western; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000502:physiology*; D007172:Erectile Dysfunction / Q000150:complications* / Q000188:drug therapy*; D005246:Feedback; D007150:Immunohistochemistry; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D016133:Polymerase Chain Reaction; D012313:RNA / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000187:drug effects*
D047228:Angiotensin II Type 1 Receptor Blockers; D017931:DNA Primers; D018076:DNA, Complementary; D012313:RNA; D019808:Losartan