Intact renal afferent arteriolar autoregulatory responsiveness in db/db mice.

The db/db mouse is a genetic model of type 2 diabetes that exhibits progressive renal disease. Obesity, hyperglycemia, and albuminuria (822 +/- 365 vs. 28 +/- 8 microg/day) are evident in 18-wk-old db/db compared with db/m (lean littermate control) mice. Our goal was to determine the blood pressure (BP) phenotype of the db/db mouse. Mean arterial BP measured in conscious mice by radiotelemetry was not different between db/db (n = 9) and db/m (n = 12) mice, averaging 113 +/- 3 and 112 +/- 2 mmHg, respectively. The circadian BP profile of db/db mice was shifted to the left and exhibited a significant reduction in amplitude compared with db/m mice. Heart rate (487 +/- 9 vs. 542 +/- 7 beats/min; P < 0.05) and locomotor activity were significantly reduced in db/db compared with db/m mice. We tested the hypothesis that intact afferent arteriole (AA) responsiveness to increases in renal artery pressure (RAP) and angiotensin (ANG) II sensitivity contributes to normal BP in this diabetic model. AA diameters of in vitro blood-perfused juxtamedullary nephrons of db/db mice (15.7 +/- 0.5 microm; n = 38) were significantly larger than those of db/m mice (12.5 +/- 0.4 microm; n = 37). AA responses to increases in RAP and ANG II were not different between kidneys of db/db and db/m mice. Significant AA vasoconstriction to 1 nM ANG II was observed in kidneys of db/db mice (-11 +/- 4%), while 10 nM ANG II decreased AA diameter in both groups [db/db, -20 +/- 4%, (n = 12); db/m, -26 +/- 4% (n = 12)]. In summary, AA responses to increases in renal perfusion pressure and ANG II remain intact in db/db mice. Diabetic renal disease occurs in db/db mice independently of elevated BP.