High salt diet ameliorates effects of angiotensin converting enzyme inhibition in spontaneously hypertensive streptozotocin diabetic rats

Clin Exp Pharmacol Physiol. 1990 Mar;17(3):229-34. doi: 10.1111/j.1440-1681.1990.tb01312.x.

Abstract

1. To dissociate the effects on the development of diabetic renal injury of angiotensin converting enzyme (ACE) inhibition per se, and a reduction in systemic blood pressure, we have studied the effects of chronic ramapril treatment in streptozotocin diabetic spontaneously hypertensive rats, with modulation of the hypotensive effect by a high salt diet. 2. Three weeks following uninephrectomy and induction of diabetes with streptozotocin, spontaneously hypertensive rats were allocated to three treatment groups. Groups 1 and 2 received 1% sodium chloride and Group 3 water as drinking solution. Groups 2 and 3 received 0.4 mg/kg per day ramapril in drinking solution over the subsequent 2 month study period. 3. Sodium chloride drinking solution (1%) completely prevented any hypotensive effect of ramapril. Blood pressure was reduced in Group 3 rats over the entire period of study, when compared with Group 2 rats (P less than 0.001). 4. Urinary protein excretion progressively increased in Group 1 and 2 rats, and was significantly reduced (P less than 0.001) in Group 3. After 2 months treatment, urinary protein (expressed as mean and s.e.m.) was 160 +/- 30 mg/day in Group 1, 240 +/- 50 mg/day in Group 2, and 60 +/- 11 mg/day in Group 3. 5. Angiotensin converting enzyme inhibition per se was not associated with a reduced protein excretion in diabetic nephropathy, requiring concomitant control of systemic blood pressure to become renoprotective.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Pressure / drug effects*
  • Bridged Bicyclo Compounds / pharmacology*
  • Bridged-Ring Compounds / pharmacology*
  • Diabetes Mellitus, Experimental / physiopathology*
  • Glomerular Filtration Rate / drug effects*
  • Male
  • Proteinuria / etiology
  • Ramipril
  • Rats
  • Rats, Inbred SHR
  • Sodium, Dietary / pharmacology
  • Streptozocin
  • Time Factors

Substances

  • Bridged Bicyclo Compounds
  • Bridged-Ring Compounds
  • Sodium, Dietary
  • Streptozocin
  • Ramipril