Reduction of salt sensitivity in stroke-prone spontaneously hypertensive rats administered an AT1 receptor antagonist during suckling

Am J Hypertens. 2006 Sep;19(9):979-84. doi: 10.1016/j.amjhyper.2006.03.004.

Abstract

Background: In this study, antihypertensive therapy was started during suckling and the effect on blood pressure (BP) and salt sensitivity of stroke-prone spontaneously hypertensive rats (SHRSP) was determined.

Methods: The SHRSP were treated with an AT1 receptor antagonist (losartan: 100 mg/L in drinking water) from 2 to 4 weeks of age. After stopping treatment at 4 weeks of age, the control group and the losartan group were fed a commercial diet with tap water ad libitum until 10 weeks of age. Both the control and losartan groups were switched to 1% saline at the age of 10 weeks.

Results: Salt loading was started at 10 weeks of age, with BP levels of 203+/-3 and 199+/-6 mm Hg for the control group and the losartan group, respectively, at that age. After 4 weeks of salt loading, BP levels were 253+/-7 mm Hg in the control group and 242+/-5 mm Hg in the losartan group, showing a mild elevation in the losartan group. The life span of the losartan group (104+/-78 days) was significantly greater than that of the control group (37+/-17 days). Plasma aldosterone concentrations of the losartan group were lower than those of the control group at 4 and 15 weeks of age.

Conclusions: We have demonstrated the renin-angiotensin-aldosterone system may play a key role in the establishment of end-organ salt sensitivity, and the period of lactation in critical for salt sensitivity in later life.

MeSH terms

  • Albuminuria / chemically induced
  • Aldosterone / blood
  • Analysis of Variance
  • Angiotensin II Type 1 Receptor Blockers / pharmacology*
  • Animals
  • Animals, Suckling
  • Antihypertensive Agents / pharmacology
  • Biomarkers / blood
  • Biomarkers / urine
  • Blood Pressure / drug effects
  • Disease Models, Animal
  • Losartan / pharmacology
  • Male
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Renin / blood
  • Renin / drug effects
  • Sodium Chloride, Dietary / adverse effects
  • Sodium Chloride, Dietary / pharmacology*
  • Stroke / chemically induced
  • Stroke / physiopathology*
  • Time Factors

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Antihypertensive Agents
  • Biomarkers
  • Sodium Chloride, Dietary
  • Aldosterone
  • Renin
  • Losartan