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

Michael W. Brands, Sharyn M. Fitzgerald

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


Little is known about how hyperglycemia in diabetes directly affects renal and cardiovascular function. Therefore, we modified the streptozotocin-model of Type I diabetes in rats to enable chronic cardiovascular study at the earliest stages of diabetes, before there was time for development of vascular 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 plasma renin activity (PRA). Mean arterial pressure (MAP) also increased, but the amplitude was modest. Moreover, we measured significant increases in glomerular filtration rate (GFR) and renal plasma flow, and also showed that endothelially 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 pressor response to the onset of diabetes. Our results showed that induction of diabetes in rats with chronic NO synthase inhibition caused a marked and progressive increase in MAP. In addition, PRA increased progressively under those conditions and the increase in GFR was prevented. This suggests that NO may work to keep arterial pressure in control 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 interactions and the role of renal vascular resistance and other factors in mediating the hypertensive response remain unknown.

Original languageEnglish (US)
Pages (from-to)126S-131S
JournalAmerican journal of hypertension
Issue number6 II
StatePublished - 2001


  • GFR
  • Hypertension
  • Renal vascular resistance
  • Renin

ASJC Scopus subject areas

  • Internal Medicine


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