saralasin and renin-inhibitory-peptide--4-amino-5-cyclohexyl-3-hydroxypentanoic-acid

We produced maximal or near-maximal acute intrarenal blockade of the renin-angiotensin system (RAS) by combining inhibitors. Intrarenal infusion of the renin inhibitor, ACRIP, the converting enzyme inhibitor, teprotide, and saralasin were administered individually or combined in random order. The inhibitors were infused for 20 min in doses that did not produce systemic effects in uninephrectomized conscious dogs in sodium balance at 10 meq/day. Significant increases in urine flow rate (UV; F = 97, P less than 0.0001), urinary sodium excretion (UNaV; F = 220, P less than 0.0001), glomerular filtration rate (GFR; F = 64, P less than 0.0001), and renal plasma flow (RPF; F = 108, P less than 0.0001) were observed with each blocker, whether alone or in combination except that ACRIP alone did not alter GFR or RPF. The increase in renal function was related to the number of blockers (3 greater than 2 greater than 1). With the three blockers combined UV increased approximately sixfold (from 0.5 +/- 0.06 to 2.9 +/- 0.03 ml/min), UNaV approximately 10-fold (from 3 +/- 0.4 to 34 +/- 2.8 mueq/min), GFR from 31 +/- 2 to 49 +/- 2 ml/min, RPF from 59 +/- 1 to 120 +/- 4 ml/min, and fractional excretion of sodium from 0.06 +/- 0.01 to 0.5 +/- 0.4% (all P less than 0.001). These changes did not occur where the inhibitors were infused systemically and the changes during intrarenal blocker administration were blocked completely with co-administration of angiotensin II intrarenally. The intrarenal RAS is a potent physiological regulator of renal function.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Angiotensin II; Animals; Dogs; Female; Hemodynamics; Hormones; Injections; Injections, Intravenous; Kidney; Oligopeptides; Renal Circulation; Renin; Renin-Angiotensin System; Saralasin; Teprotide

All the components of the renin-angiotensin system are present within the kidney and intrarenal effects have been demonstrated. We have previously shown that intrarenally confined doses of angiotensin II (Ang II) decreased renal excretory and haemodynamic function. In the present study we investigated an increase in renal excretory and haemodynamic function in response to intrarenally confined doses of the renin inhibitor ACRIP to inhibit renin, teprotide to inhibit the angiotensin converting enzyme (ACE) and saralasin to block Ang II receptors. We studied the effects of combined intrarenal blockade of the renin-angiotensin system in five female uninephrectomized conscious dogs on a sodium metabolic balance of 5 mmol/day. We infused ACRIP, teprotide and saralasin combined over 30 min in doses confined to the kidney, and again with an intrarenally confined dose of Ang II. There were no changes in renal function during the control study. During the combined infusion (ACRIP + teprotide + saralasin), the urine flow rate increased from 0.4 +/- 0.1 to 0.9 +/- 0.1 ml/min (P less than 0.001), urinary sodium excretion increased from 6.4 +/- 0.4 to 30.2 +/- 2.5 mumol/min (P less than 0.0001), the glomerular filtration rate increased from 29.3 +/- 0.7 to 42.0 +/- 1.2 ml/min (P less than 0.0001), renal plasma flow increased from 60.3 +/- 0.8 to 139.6 +/- 1.8 ml/min (P less than 0.001) and the fractional sodium excretion increased from 0.1 +/- 0.01 to 0.5 +/- 0.04% (P less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Angiotensin II; Animals; Dogs; Drug Interactions; Female; Hemodynamics; Kidney; Nephrectomy; Oligopeptides; Renin; Renin-Angiotensin System; Saralasin; Teprotide