Effect of the protease inhibitor aprotinin on renal hemodynamics in the pig.
Aprotinin, the serine protease inhibitor that also inhibits glandular (urinary) kallikrein, or vehicle was infused into the aorta above the renal arteries of anesthetized pigs. Renal hemodynamic and functional parameters were followed over time and during hemorrhagic hypotension. Both renal cortical blood flow and glomerular filtration rate were maintained in vehicle-treated animals at mean arterial pressures as low as 70 mm Hg. As long as renal cortical blood flow and glomerular filtration rate were maintained during the progressive hypotension, urinary excretion rate of kallikrein (as defined by kinin-generating activity) was increased. In contrast, all aprotinin-treated animals had a decreased excretion rate, and the renal cortical blood flow declined with the mean arterial pressure during hemorrhage. The pattern of glomerular filtration rate and plasma renin activity was comparable in both aprotinin-treated and vehicle-treated hemorrhaged animals. Our findings suggest that the endogenous renal kallikrein-kinin system is required for functional renal vasodilatation to maintain renal cortical blood flow during hemorrhage and is therefore directly or indirectly responsible for adjustment of preglomerular resistance.
Maier
M
M
Starlinger
M
M
Zhegu
Z
Z
Rana
H
H
Binder
B R
BR
D000704:Analysis of Variance; D000818:Animals; D007611:Aprotinin / Q000008:administration & dosage / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D006470:Hemorrhage / Q000503:physiopathology; D007022:Hypotension / Q000503:physiopathology; D007263:Infusions, Parenteral; D007610:Kallikreins / Q000037:antagonists & inhibitors; D007672:Kidney Cortex / Q000098:blood supply; D014677:Pharmaceutical Vehicles / Q000008:administration & dosage; D011480:Protease Inhibitors; D012039:Regional Blood Flow; D012079:Renal Circulation / Q000187:drug effects*; D013552:Swine / Q000502:physiology*
D014677:Pharmaceutical Vehicles; D011480:Protease Inhibitors; D007611:Aprotinin; D007610:Kallikreins