Combined intrarenal blockade of the renin-angiotensin system in the conscious dog.
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)
Siragy
H M
HM
Department of Internal Medicine, University of Virginia School of Medicine, Charlottesville 22908.
Howell
N L
NL
Peach
M J
MJ
Carey
R M
RM
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D004285:Dogs; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006728:Hormones / Q000378:metabolism; D007267:Injections; D007275:Injections, Intravenous; D007668:Kidney / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D012079:Renal Circulation / Q000187:drug effects; D012084:Renin-Angiotensin System / Q000187:drug effects; D012504:Saralasin / Q000494:pharmacology; D013722:Teprotide / Q000494:pharmacology; D000092502:Renin Inhibitors
D000804:Angiotensin II; D006728:Hormones; D009842:Oligopeptides; D012504:Saralasin; D013722:Teprotide; D000092502:Renin Inhibitors; C051529:renin inhibitory peptide, 4-amino-5-cyclohexyl-3-hydroxypentanoic acid