Arterial pressure control at the onset of type I diabetes: The role of nitric oxide and the renin-angiotensin system

Little is known about how hyperglycemia in diabetes directly affects renal and cardiovascular function. Therefore, we modified the streptozotocin-mode l of Type I diabetes in rats to enable chronic cardiovascular study at the earliest stages of diabetes, before there was time for development of vascu lar structural changes. We showed that the onset of diabetic hyperglycemia increased total peripheral resistance, decreased skeletal muscle blood flow , increased thromboxane production, and caused a transient increase in plas ma renin activity (PRA). Mean arterial pressure (MAP) also increased, but t he amplitude was modest. Moreover, we measured significant increases in glo merular filtration rate (GFR) and renal plasma flow, and also showed that e ndothelially mediated vasodilation in skeletal muscle was not impaired. We then tested the hypothesis that nitric oxide (NO) was playing an important role in counteracting a presser response to the onset of diabetes. Our resu lts showed that induction of diabetes in rats with chronic NO synthase inhi bition caused a marked and progressive increase in MAP. In addition, PRA in creased progressively under those conditions and the increase in GFR was pr evented. This suggests that NO may work to keep arterial pressure in contro l at the onset of hyperglycemia very early in the development of diabetes, possibly by facilitating renal vasodilation and by suppressing activity of the renin-angiotensin system. However, the mechanisms for these interaction s and the role of renal vascular resistance and other factors in mediating the hypertensive response remain unknown. Am J Hypertens 2001;14:126S-131S (C) 2001 American Journal of Hypertension, Ltd.