Hypertension induced by subchronic treatment with l-name is prevented by eta receptor blockade in the rat

Academic Article

Abstract

  • Experiments were designed to determine whether the hypertension produced by subchronic (4 day) inhibition of NO synthase with L-NAME can be reversed by administration of an endothelin ETA receptor antagonist. Male, Sprague-bawley rats were acclimated to metabolism cages and baseline measurements of 24 hr excretory function were obtained along with tail cuff pressures and a blood sample. Rats were then provided L-NAME in the drinking water (50 mg/100 ml or approx. 60 mg/kg/day) with or without the orally active ETA receptor antagonist. A-127722 (30 mg/kg/day). After 4 days, tail cuff pressures were significantly elevated above baseline in the LNAME-treated group (A 23+5 mmHg) whereas the hypertension was significantly less in rats receiving L-NAME plus A-127722 (A 13±2 mmHg). L-NAME alone did not influence water intake although the combination of L-NAME + A-127722 reduced water intake by roughly onethird. To test whether the resulting reduction in L-NAME and A-127722 intake influenced the degree of hypertension, A-127722 was administered via the rat's food while receiving L-NAME in the drinking water. In this case, water intake was not reduced yet L-NAME hypertension was blocked (A 7±4 mmHg). Furthermore, reducing the L-NAME concentration to deliver approx. 30 mg/kg/day (without A-127722) produced a similar degree of hypertension as the higher dose (A 26±6 mmHg). These results suggest an interaction between the endothelin and NO systems and support the hypothesis that subchronic L-NAME hypertension is maintained, at least in part, by activation of ET, receptors.
  • Authors

    Published In

  • The FASEB Journal  Journal
  • Author List

  • Pollock DM; Polakowski JS
  • Volume

  • 10
  • Issue

  • 3