Effects of chronic administration of an angiotensin-converting enzyme inhibitor on angiotensin-converting enzyme activity in the pars recta of rabbits.
1. To determine whether chronic angiotensin-converting enzyme inhibition induces a decrease in proximal tubular angiotensin-converting enzyme activity, urine and blood samples were collected in conscious New Zealand rabbits before and after 16 days administration in drinking water of low doses of captopril (2.6 +/- 0.6 mg 24 h-1 kg-1), high doses of captopril (7.6 +/- 0.9 mg 24 h-1 kg-1) or no captopril (controls). The kidneys were then removed and angiotensin-converting enzyme activity was determined in isolated pars recta of microdissected nephrons as pmol of tritiated hippurylglycylglycine substrate hydrolysed min-1 of incubation and mm-1 of tubule. 2. Both low and high doses of captopril significantly decreased plasma angiotensin-converting enzyme activity and increased plasma renin activity, thus indicating an effective inhibition of circulating angiotensin-converting enzyme. Both low and high doses of captopril also significantly decreased mean arterial pressure and increased water intake and urine flow rate. Neither dose modified creatinine clearance and absolute and fractional sodium excretion. 3. None of the doses altered urinary kallikrein excretion. Urinary excretion of kinins was increased by 98.7% compared with control rabbits by the high dose of captopril (402 +/- 152 vs 251 +/- 104 ng/24 h, P less than 0.01) but was unchanged by the low dose of captopril. 4. Angiotensin-converting enzyme activity in the pars recta was lower in rabbits given the high dose of captopril than in control rabbits (17.6 +/- 7.2 vs 37.3 +/- 9.0 pmol min-1 mm-1, P less than 0.01) but was not decreased in rabbits given the low dose of captopril (40.4 +/- 5.0 pmol min-1 mm-1).(ABSTRACT TRUNCATED AT 250 WORDS)
Praddaude
F
F
Laboratory of Physiology, Medical School, Paul Sabatier University, Toulouse, France.
Tran-Van
T
T
Marchetti
J
J
Girolami
J P
JP
Ader
J L
JL
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000008:administration & dosage / Q000494:pharmacology*; D003404:Creatinine / Q000652:urine; D004305:Dose-Response Relationship, Drug; D007610:Kallikreins / Q000652:urine; D007687:Kidney Tubules, Proximal / Q000201:enzymology*; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D011817:Rabbits; D012083:Renin / Q000097:blood; D012964:Sodium / Q000652:urine; D014563:Urodynamics / Q000187:drug effects; D014867:Water / Q000378:metabolism
D014867:Water; D002216:Captopril; D012964:Sodium; D003404:Creatinine; D007703:Peptidyl-Dipeptidase A; D007610:Kallikreins; D012083:Renin