Atrial natriuretic peptide prevents diabetes-induced endothelial dysfunction

Atrial natriuretic peptide (ANP) exerts beneficial effects on the cardiovascular system in part by exerting antioxidant activity. Given that oxidant stress is a key cause of endothelial dysfunction in diabetes, we investigated whether ANP improves endothelial function in rats with diabetes. Rats were injected with streptozotocin (55 mg/kg iv) to induce type 1 diabetes or the citrate vehicle as controls (n= 12). After 4 weeks the diabetic rats were treated with ANP (10 pmol/kg/min sc, n= 12) or the antioxidant tempol (1.5 mmol/kg/day sc, n= 11), both by osmotic minipump, ramipril (1 mg/kg per day in the drinking water) or remained untreated (n= 11). After a further 4 weeks, anaesthetised rats were killed by exsanguination and the thoracic aortae collected for examination of vascular activity and measurement of superoxide generation. Diabetic rats showed elevated plasma glucose concentration (45 ± 3 mM) compared to controls (10 ± 1 mM) and this was not affected by ANP (43 ± 3 mM), ramipril (41 ± 2 mM) or tempol (43 ± 2 mM). Endothelium-dependent relaxation ex vivo in response to acetylcholine was impaired in diabetic rats (R max= 66 ± 4%) compared to control rats (R max= 94 ± 1%) but treatment with ANP (R max= 80 ± 4%), ramipril (R max= 88 ± 2%) or tempol (R max= 81 ± 5%) significantly improved those responses. Relaxant responses to the endothelium-independent vasodilator sodium nitroprusside were enhanced by treatment of diabetic rats with ANP or ramipril and their combination; but not by tempol. Superoxide generation was significantly elevated in aorta from untreated diabetic rats (649 ± 146% of control).