Effect of intrarenal renin inhibition on renal hemodynamics and excretory function.
This study was designed to investigate in sodium-depleted monkeys the renal hemodynamic and excretory effects resulting from blockade of the renin-angiotensin system induced by intrarenal infusion of the primate-selective renin inhibitor A-65317. Intrarenal infusion of A-65317 (n = 6) at a dose of 0.01 micrograms.kg-1.min-1 elicited an increase (P less than 0.05) in renal blood flow (RBF) from 43.5 +/- 2.7 to 49.4 +/- 4.4 ml/min and glomerular filtration rate (GFR) from 6.3 +/- 0.3 to 6.9 +/- 0.4 ml/min, with no significant changes in mean arterial pressure (MAP) or plasma renin activity (PRA). Increases (P less than 0.05) in the urine flow rate (0.18 +/- 0.04 to 0.28 +/- 0.04 ml/min) and the fractional excretion of sodium (0.18 +/- 0.06 to 0.35 +/- 0.13%) were also observed. After a recovery period, the intrarenal infusion dose of A-65317 was increased to 0.1 microgram.kg-1.min-1 and RBF increased (P less than 0.05) from 42.9 +/- 3.9 to 53.0 +/- 3.7 ml/min in conjunction with a significant 85 +/- 4% inhibition of PRA and a 14 +/- 4 mmHg reduction in MAP. GFR and electrolyte excretion remained at control levels. Intrarenal infusion of vehicle (n = 6) had no significant effect on any of the variables studied. In a separate group of monkeys, intravenous (iv) infusion of A-65317 at 0.01 microgram.kg-1.min-1 (n = 5) did not result in significant changes from control.(ABSTRACT TRUNCATED AT 250 WORDS)
Verburg
K M
KM
Cardiovascular Research Division, Abbott Laboratories, Abbott Park, Illinois 60064.
Kadam
J R
JR
Young
G A
GA
Rosenberg
S H
SH
Kleinert
H D
HD
D000804:Angiotensin II / Q000502:physiology; D000818:Animals; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006639:Histidine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D007261:Infusions, Intra-Arterial; D007262:Infusions, Intravenous; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D008252:Macaca fascicularis; D008297:Male; D010080:Oxazoles / Q000008:administration & dosage / Q000494:pharmacology; D023303:Oxazolidinones; D012079:Renal Circulation / Q000187:drug effects* / Q000502:physiology; D012083:Renin / Q000378:metabolism / Q000502:physiology*; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D012964:Sodium / Q000652:urine; D014554:Urination / Q000187:drug effects* / Q000502:physiology; D000092502:Renin Inhibitors
D000804:Angiotensin II; D006639:Histidine; D010080:Oxazoles; D023303:Oxazolidinones; D012083:Renin; D012964:Sodium; D000092502:Renin Inhibitors; C065076:A 65317