Enhanced renal sensitivity to angiotensin actions in diabetes mellitus in the rat.
The renin-angiotensin system (RAS) has been implicated in the pathogenesis of diabetic nephropathy. In diabetes, renal RAS components are dysregulated, potentially increasing renal RAS effects. To explore the renal RAS, studies were conducted in control and diabetic rats. In both groups, intravenous angiotensin (ANG) I and ANG II produced similar increases in mean arterial pressure (MAP). In contrast, glomerular filtration rate defined only in diabetic rats. Renal plasma flow fell in both groups but decreased more in diabetic rats. Additional groups were given the same dose of ANG I directly into the left renal artery, and hemodynamics were studied in the treated and untreated kidneys. In contrast to the intravenous studies, intra-arterial ANG I had no effect on MAP in either group. The renal hemodynamic effects were similar to those in intravenous studies. Additionally, diabetic rats exhibited enhanced hemodynamic sensitivity in the untreated kidney, suggesting that renal effects could occur at nonpressor concentrations of circulating ANG II. Thus renal (but not systemic) responsiveness to angiotensins is enhanced in diabetic rats.
Kennefick
T M
TM
Division of Nephrology and Hypertension, Oregon Health Sciences University, Portland, USA.
Oyama
T T
TT
Thompson
M M
MM
Vora
J P
JP
Anderson
S
S
D000803:Angiotensin I / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D000804:Angiotensin II / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects
D000804:Angiotensin II; D000803:Angiotensin I