Role of kinin and renal ANG II blockade in acute effects of ACE inhibitors in low-renin hypertension

Am J Physiol. 1997 Feb;272(2 Pt 2):H679-87. doi: 10.1152/ajpheart.1997.272.2.H679.

Abstract

In conscious deoxycorticosterone acetate (DOCA) salt-hypertensive dogs, the angiotensin-converting enzyme (ACE) inhibitors captopril and imidaprilat significantly decreased mean arterial pressure (MAP) and significantly increased urine flow rate, effective renal plasma flow (ERPF), glomerular filtration rate, and urinary sodium excretion. However, the angiotensin type 1 (AT1) receptor antagonist losartan caused a significant increase only in urinary sodium excretion without significant changes in MAP, urine flow rate, ERPF, and glomerular filtration rate. Simultaneous infusion of a bradykinin receptor antagonist inhibited the ACE inhibitor-induced reduction in MAP and increase in ERPF. DOCA salt treatment markedly suppressed plasma angiotensin II (ANG II) concentration (P < 0.001), although it decreased renal ANG II content only slightly (P < 0.05). Comparison of the expression of renal AT1 receptor mRNA in control kidneys with that in DOCA salt-hypertensive kidneys revealed no significant change. These results suggest that, in low-renin hypertension, inhibition of the relatively maintained ANG II production in the kidney participates in the natriuretic action of ACE inhibitors. However, hypotensive and other renal effects are mainly due to the action of bradykinin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / antagonists & inhibitors*
  • Angiotensin II / blood
  • Angiotensin II / metabolism
  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology*
  • Animals
  • Blood Pressure
  • Bradykinin Receptor Antagonists
  • Cyclooxygenase Inhibitors / pharmacology
  • Desoxycorticosterone
  • Dogs
  • Eicosanoids / urine
  • Hypertension / chemically induced
  • Hypertension / metabolism*
  • Hypertension / physiopathology*
  • Kidney / metabolism*
  • Kidney / physiopathology
  • Kinins / physiology*
  • Kinins / urine
  • Male
  • Renin / blood*
  • Sodium Chloride
  • Thromboxane-A Synthase / antagonists & inhibitors

Substances

  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Bradykinin Receptor Antagonists
  • Cyclooxygenase Inhibitors
  • Eicosanoids
  • Kinins
  • Angiotensin II
  • Desoxycorticosterone
  • Sodium Chloride
  • Renin
  • Thromboxane-A Synthase