Nifedipine versus fosinopril in uninephrectomized diabetic rats.
Antihypertensive agents have been shown to exert inequivalent effects on glomerular injury in experimental renal disease models. To compare the consequences of dissimilar antihypertensive regimens on the development of diabetic glomerulopathy, studies were performed in three groups of uninephrectomized moderately hyperglycemic diabetic rats. One group (DM) received no therapy except insulin. The remaining groups received insulin and either the angiotensin I converting enzyme inhibitor, fosinopril (FOS), or the calcium channel blocker, nifedipine (NIF). Both drugs lowered blood pressure comparably. At four to eight weeks, DM rats exhibited elevation of the single nephron glomerular filtration rate (SNGFR), due to elevations of the glomerular capillary plasma flow rate (QA) and the glomerular capillary hydraulic pressure (PGC). Neither NIF nor FOS affected values for SNGFR or QA. However, while FOS lowered PGC and increased Kf, NIF did not affect these parameters. In longer term (8 month) studies, DM rats exhibited progressive albuminuria and glomerular sclerosis. FOS markedly limited development of albuminuria and glomerular injury, but NIF was ineffective in limiting either parameter of glomerular injury. Thus, in contrast to the beneficial effects of converting enzyme inhibitors, chronic calcium channel blockade with nifedipine fails to limit PGC or glomerular injury in diabetic rats. These findings lend further support to the concept that different classes of antihypertensive agents are not equally effective in protecting against diabetic glomerulopathy.
Anderson
S
S
Renal Division, Brigham and Women's Hospital, Boston, Massachusetts.
Rennke
H G
HG
Brenner
B M
BM
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000473:pathology / Q000503:physiopathology*; D017328:Fosinopril; D006439:Hemodynamics; D008137:Longitudinal Studies; D009392:Nephrectomy / Q000379:methods; D009543:Nifedipine / Q000494:pharmacology*; D011392:Proline / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation
D000806:Angiotensin-Converting Enzyme Inhibitors; D011392:Proline; D009543:Nifedipine; D017328:Fosinopril