Combined intrarenal renin-angiotensin blockade alters renal function and this is reversed by angiotensin II.
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)
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; D004347:Drug Interactions; D005260:Female; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D009392:Nephrectomy; D009842:Oligopeptides / Q000494:pharmacology; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology; D012504:Saralasin / Q000494:pharmacology; D013722:Teprotide / Q000494:pharmacology; D000092502:Renin Inhibitors
D000804:Angiotensin II; D009842:Oligopeptides; D012504:Saralasin; D013722:Teprotide; D000092502:Renin Inhibitors; C051529:renin inhibitory peptide, 4-amino-5-cyclohexyl-3-hydroxypentanoic acid