Autonomy of the renin system in type II diabetes mellitus: dietary sodium and renal hemodynamic responses to ACE inhibition

Kidney Int. 1997 Sep;52(3):771-7. doi: 10.1038/ki.1997.394.

Abstract

Recognition that non-insulin-dependent diabetes mellitus (NIDDM) is a leading cause of end-stage renal disease (ESRD), and a focus of recent therapeutic and genetic studies on the renin system have rekindled interest in mechanisms by which angiotensin converting enzyme (ACE) inhibitors influence the diabetic kidney. We evaluated the renal hemodynamic status of 19 hypertensive patients with NIDDM under controlled sodium balance, low (10 mmol/day for 5 to 7 days) or high (200 mmol/day for 5 to 7 days). The renal plasma flow (RPF) response to ACE inhibition and to angiotensin II (Ang II) infusion was measured as para-aminohippurate (PAH) clearance before and during enalapril administration (10 mg b.i.d. for 3 days). Our premise was that if renal vasodilation induced by ACEI involves kinins, prostaglandins, and/or nitric oxide, vasoconstrictor responses to Ang II would be blunted. Conversely, if the dominant ACE inhibitor action were a reduction in Ang II formation, the consequence would be up-regulation and an enhanced vasoconstrictor response to exogenous Ang II. RPF in NIDDM on a high-salt diet was lower than in age-matched controls (477 +/- 25 vs. 551 +/- 25 ml/min/1.73 m2; P = 0.02). Enalapril increased RPF in NIDDM to 511 +/- 29 ml/min/1.73 m2 (P < 0.05) and enhanced renal vasoconstrictor responses to Ang II infusion, from -68 +/- 9 to -106 +/- 18 ml/min/1.73 m2 (P = 0.03). Baseline plasma renin activity (PRA) and plasma aldosterone significantly exceeded matched normotensive controls (1.1 +/- 0.5 vs. 0.3 +/- 0.1 ng AI/ml/hr and 10 +/- 0.9 vs. 4.1 +/- 0.5 ng/dl, P < 0.01, respectively). Conversely all measures in studies on a low-salt diet were normal. Our findings indicate that: (1) NIDDM with hypertension is associated with reduced RPF when dietary salt intake is high, (2) reduced Ang II formation is the dominant mechanism of ACEI-induced renal vasodilation in hypertensives with NIDDM; and (3) the sustained renal hemodynamic responses to ACE inhibition despite high-salt balance, and the increased PRA suggest an autonomous renin-angiotensin system suppressed subnormally by a high salt diet in patients with NIDDM despite greater volume expansion.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aldosterone / blood
  • Angiotensin II / pharmacology
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology*
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / metabolism*
  • Diet, Sodium-Restricted*
  • Enalapril / pharmacology*
  • Female
  • Hemodynamics / drug effects
  • Humans
  • Hypertension / blood
  • Hypertension / complications
  • Male
  • Middle Aged
  • Renal Circulation / drug effects*
  • Renin / blood
  • Renin / physiology*
  • Renin-Angiotensin System / physiology

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Angiotensin II
  • Aldosterone
  • Enalapril
  • Renin