Effect of Angiotensin 1-7 Peptide Agonist AVE 0991 on Diabetic Endothelial Dysfunction in an Experimental Animal Model: A Possible Tool to Treat Diabetic Erectile Dysfunction

Abstract

Background

The renin-angiotensin system and its metabolites are crucial in the pathogenesis and progression of complications of diabetes.

Aim

In this study, we aimed to evaluate the effect of angiotensin 1-7 non-peptide agonist AVE 0991 (576 ug/kg/day i.p.) on diabetic endothelial dysfunction.

Materials and methods

In this experimental animal study, we investigated the effects of angiotensin 1-7 non-peptide agonist AVE 0991 (576 ug/kg/day i.p.) treatment in male Wistar rats. Diabetes was created via injecting streptozotocin (55 mg/kg/i.p., single dose). Following the cavernous tissue submaximal phenylephrine contraction, relaxation responses were obtained by applying electrical field stimulation (0.5 ms, 40 V) for 15 seconds at 2, 4, 8, 16, 32, and 64 Hz, with two-minute intervals, respectively. To evaluate the effect of nitric oxide, the responses were compared by incubating with 100 mM N(gamma)-nitro-L-arginine methyl ester (L-NAME) for 20 minutes. Additionally, Y-27632 and sodium nitroprusside responses were evaluated in tissues contracted with submaximal doses of phenylephrine.

Results

Following a submaximal contraction of phenylephrine in the aorta rings, relaxation responses obtained with acetylcholine, sodium nitroprusside, and Y-27632 were impaired in diabetic rats; however, significant results were obtained with treatment. Although there was no significance between the groups in the electrical field stimulation responses, there was a significant dose-dependent difference in the treatment group in this parameter after L-NAME, sodium nitroprusside, and Y-27632 relaxation.

Conclusions

We determined that treatment with a non-peptide receptor antagonist of angiotensin 1-7, an enzyme detected in the aortic and cavernosum endothelium, may be a promising alternative for treating the complications of diabetes.

 

Coşkunsever D, Olukman M, Jannini E, Sansone A, Varrassi G. (November 13, 2023) Effect of Angiotensin 1-7 Peptide Agonist AVE 0991 on Diabetic Endothelial Dysfunction in an Experimental Animal Model: A Possible Tool to Treat Diabetic Erectile Dysfunction. Cureus 15(11): e48770. doi:10.7759/cureus.48770