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 ail stenotic (n = 11) but not in nonstenotic kidney I-123-hippurate renograms (n = 6), Renographic changes correlated significantly with initiation of intrarenal I-131-hippurate retention, a decrease in mean arterial pressure (MAP), renal extraction of I-131-hippurate and I-125-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 I-131-hippurate and I-125-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. Conclusion: 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 decease 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.