Long-term effects of antihypertensive regimens on renal hemodynamics and proteinuria.
The long-term effects of different antihypertensive regimens were studied in uninephrectomized beagles with alloxan-induced diabetes mellitus. Mean arterial pressure (MAP) was elevated (P < 0.05) in untreated diabetic dogs. Treatment of diabetic dogs with an angiotensin converting enzyme inhibitor (ACEI; lisinopril), a calcium antagonist (CA;TA-3090), or both lowered MAP. At one year, the RBF, GFR, and SNGFR were similarly elevated (P < 0.05) in all groups of diabetic dogs. The increase in SNGFR present in untreated diabetic dogs was primarily attributable to an increased (P < 0.05) glomerular capillary pressure (PGC). Treatment with lisinopril lowered the PGC to a mean value that was indistinguishable from that for nondiabetic dogs. In contrast, diabetic dogs treated with TA-3090 had an elevated PGC. While untreated diabetic dogs exhibited marked increases in glomerular volume (P < 0.05 vs. nondiabetic dogs), treatment with lisinopril and TA-3090, either alone or in combination, blunted the extent of glomerular hypertrophy observed in diabetic dogs (P < 0.05 vs. untreated diabetic dogs). Proteinuria was similarly reduced (P < 0.05 vs. untreated diabetic dogs) in dogs treated with lisinopril and TA-3090. Combination therapy of diabetic dogs produced a further significant (P < 0.05) decrement in proteinuria. We conclude that although treatment of diabetic dogs with either lisinopril or TA-3090 results in differential effects on PGC; each produces a similar decrement in proteinuria. Further, combination therapy has a greater effect on proteinuria than either agent alone.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens.
S A
SA
Brown
C L
CL
Walton
P
P
Crawford
G L
GL
Bakris
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000503:physiopathology*; D004110:Diltiazem / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004151:Dipeptides / Q000008:administration & dosage / Q000627:therapeutic use*; D004285:Dogs; D004359:Drug Therapy, Combination; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006706:Homeostasis; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D017706:Lisinopril; D008297:Male; D011507:Proteinuria / Q000517:prevention & control*; D012079:Renal Circulation / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004151:Dipeptides; C056595:clentiazem; D017706:Lisinopril; D004110:Diltiazem