Angiotensin-converting enzyme inhibition-induced changes in hippurate renography and renal function in renovascular hypertension.
We studied the mechanism of angiotensin-converting enzyme (ACE) inhibition-induced changes in hippurate renography of the poststenotic kidney.


METHODS
Ten male mongrel dogs, six with unilateral and four with bilateral renal artery stenosis, were equipped with renal artery blood flow probes and catheters in the aorta, atrium and both renal veins.


RESULTS
Enalaprilat (10 mg intravenously) in conscious dogs with renal artery stenoses produced changes in all stenotic (n = 11) but not in nonstenotic kidney 123I-hippurate renograms (n = 6). Renographic changes correlated significantly with initiation of intrarenal 131I-hippurate retention, a decrease in mean arterial pressure (MAP), renal extraction of 131I-hippurate and 125I-iothalamate (r = 0.68, r = 0.62, r = 0.84, r = 0.83, respectively) but not with renal blood flow changes (r = 0.34). Furthermore, renal uptake of 131I-hippurate and 125I-iothalamate decreased in stenotic kidneys with a grade II renogram (-52 +/- 11% and -79 +/- 6%, respectively). Iodine-125-hippurate autoradiograms of stenotic kidneys during ACE inhibition showed tracer retention mainly in the proximal tubular cells. Results during osmotic diuresis supported our findings.


CONCLUSIONS
Angiotensin-converting enzyme inhibition-induced hippurate retention curves of poststenotic kidneys appear to result from a sequence of events. A decrease in MAP combined with efferent vasodilation leads to a decrease in intraglomerular capillary pressure. This decrease in pressure causes a decrease in glomerular filtration rate and proximal tubular urine flow. This decrease in turn hampers tubular hippurate transit and transport across the luminal membrane, leading to intrarenal hippurate retention and, in more severe cases, decreased renal hippurate uptake.
Visscher
C A
CA
Department of Medicine, Groningen Institute for Drug Studies, University Hospital, The Netherlands.
de Zeeuw
D
D
de Jong
P E
PE
Piers
D A
DA
Beekhuis
H
H
Groothuis
G M
GM
Huisman
R M
RM
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D001794:Blood Pressure; D003287:Contrast Media; D004285:Dogs; D015773:Enalaprilat / Q000494:pharmacology; D005919:Glomerular Filtration Rate; D006978:Hypertension, Renovascular / Q000000981:diagnostic imaging* / Q000503:physiopathology; D007457:Iodine Radioisotopes; D007465:Iodohippuric Acid; D007483:Iothalamic Acid; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D011866:Radioisotope Renography / Q000187:drug effects* / Q000379:methods; D012079:Renal Circulation; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D003287:Contrast Media; D007457:Iodine Radioisotopes; D007465:Iodohippuric Acid; D007483:Iothalamic Acid; D015773:Enalaprilat