Angiotensin responsiveness in hyperfiltering and nonhyperfiltering diabetic rats.
Renal and systemic responses to angiotensin II were studied in hyperglycemic diabetic rats (streptozotocin, 60 mg/kg, i.v.) and vehicle-injected controls at 24 h, 1 wk, 2 mo, or at 6 to 12 mo. In normal rats, the GFR was less than 0.80 mL/min per 100 g body wt (0.57 +/- 0.02 mL/min per 100 g body wt; range: 0.40 to 0.79 mL/min per 100 g body wt; N = 45). Hyperfiltration (GFR > or = 0.80 mL/min per 100 g body wt) was observed in all diabetic rats studied at 1 wk (GFR, 1.03 +/- 0.07 mL/min per 100 g body wt; N = 5; P < 0.001 versus control). However, at earlier and later times, GFR was elevated in only 8 of 18 of the diabetic rats (44%), with an overall prevalence of 56% (13 of 23). Mean arterial pressure, plasma glucose, urine volume, and filtration fraction were not different in hyperfiltering diabetic rats compared with nonhyperfiltering diabetic rats or normal controls. Angiotensin II (12.5 ng/kg per minute i.v.) had no effect on GFR in normal rats or nonhyperfiltering diabetic rats, but it normalized GFR in hyperfiltering diabetic rats (0.74 +/- 0.05 mL/min per 100 g body wt). In contrast with the renal effects of angiotensin II, blood pressure responses were similar in hyperfiltering and nonhyperfiltering diabetic rats. The findings that angiotensin II infusion caused a greater fall in GFR in hyperfiltering diabetic rats than in nonhyperfiltering diabetic rats, but that blood pressure responses were similar, suggests a localized abnormality in angiotensin responsiveness in the kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)
Wilkes
B M
BM
Department of Medicine, North Shore University Hospital-Cornell University Medical College, Manhasset, NY 11030.
Mento
P F
PF
Vernace
M A
MA
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D005919:Glomerular Filtration Rate / Q000187:drug effects* / Q000502:physiology*; D007328:Insulin / Q000627:therapeutic use; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017595:Renal Plasma Flow / Q000187:drug effects / Q000502:physiology; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology
D001786:Blood Glucose; D007328:Insulin; D000804:Angiotensin II