Angiotensin-converting enzyme inhibition with quinapril (CI-906) and captopril in spontaneously hypertensive rats with suppressed renin-angiotensin system

Methods Find Exp Clin Pharmacol. 1987 Jun;9(6):325-31.

Abstract

Renin- and nonrenin-mediated antihypertensive actions of angiotensin-converting enzyme (ACE) inhibitors were investigated in young spontaneously hypertensive rats (SHR). Renin was suppressed either by removal of 2/3 of the renal mass, deoxycorticosterone (DOC) treatment, or 1% of NaCl in drinking water. Blood pressure responses to the nonsulfhydryl ACE inhibitor quinapril (CI-906) and the sulfhydryl inhibitor captopril, given orally for 2 days each, were examined by the tail cuff method. The marked depressor responses observed in control SHR were attenuated by the different manipulations in a manner clearly related to suppression of plasma renin activity (PRA). The decrease in blood pressure falls and in PRA was smallest in partially nephrectomized SHR. The mineralocorticoid (DOC) administration or 1% NaCl reduced PRA and the responses to ACE inhibitors markedly, though not completely. In a further experiment, severe salt retention induced by DOC and NaCl in uninephrectomized SHR suppressed PRA to an unmeasurable level and prevented the depressor action of a large dose of captopril. The results suggest that in SHR the acute blood pressure-lowering effect of ACE inhibitors is completely dependent on the renin-angiotensin system. The experiments also show that this system clearly participates in the support of rapidly increasing blood pressure in young SHR.

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors / pharmacology*
  • Animals
  • Blood Pressure / drug effects
  • Captopril / pharmacology*
  • Desoxycorticosterone / pharmacology
  • Isoquinolines / pharmacology*
  • Male
  • Nephrectomy
  • Quinapril
  • Rats
  • Rats, Inbred SHR
  • Renin / blood
  • Renin-Angiotensin System / drug effects*
  • Tetrahydroisoquinolines*

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Isoquinolines
  • Tetrahydroisoquinolines
  • Desoxycorticosterone
  • Captopril
  • Renin
  • Quinapril