The Effect of Chronic Angiotensin (1-7) Treatment on Functional Responses of Isolated Resistance Arteries in...

Cardiovascular complications of diabetes mellitus (DM) are responsible for morbidity and mortality in DM patients. Recent evidence highlights the pathophysiological role of the renin-angiotensin-aldosterone system in DM. This study determined whether chronic angiotensin (1-7) (Ang (1-7); 576 μg/kg, s.c., 4 weeks) treatment improves vascular reactivity in mesenteric small resistance arteries of streptozotocin-induced diabetic rats using a wire myograph system and to investigate the underlying mechanisms. Increased sensitivity to vasoconstrictors and decreased responses to endothelium-dependent vasodilators in diabetic rats compared to control rats were partially reversed by Ang (1-7) treatment. Nω-nitro-L-arginine methyl ester (L-NAME, 10^-4 M) incubation significantly decreased vasorelaxant responses to acetylcholine (ACH, 10^-10-10^-5 M) in all groups except the diabetic group. Superoxide dismutase (SOD, 50 U/mL) incubation produced significant increases in vasorelaxant responses to ACH only in the diabetic groups. Glibenclamide (10^-5 M), 4-aminopyridine (4-AP, 5 mM), indomethacin (INDO, 10^-5 M), or catalase (CAT, 200 U/mL) incubations did not alter ACH responses in any experimental groups, whereas charybdotoxin (ChTX, 10^-7 M) or apamin (APA, 10^-7 M) produced significant decreases in ACH-induced vasorelaxation, similar in extent in the control and diabetic rats. Following co-incubation with L-NAME and INDO, ACH-induced vasorelaxation in 30 mM KCl pre-contracted arterial rings did not differ significantly between the groups. These findings indicate that improved nitric oxide bioavailability and reduced superoxide activity contribute to the beneficial vascular effects of Ang (1-7) in diabetic rat resistance arteries. Further in vivo studies are warranted to clarify its therapeutic relevance. SUMMARY: Ang (1-7) improves vascular function in diabetic rat resistance arteries. Treatment increases NO bioavailability and reduces oxidative stress. Vasoconstrictor sensitivity is decreased, improving endothelium-dependent vasorelaxation. Ang (1-7) restores vascular responses to endogenous vasoactive agents. Findings suggest Ang (1-7) as a potential target for diabetes-related vascular issues.