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1 LSU Health Sciences Center School of Medicine
2 LSU Medical Center
* To whom correspondence should be addressed. E-mail: lharris{at}lsuhsc.edu.
The db/db mouse is a genetic model of type II diabetes that exhibits progressive renal disease. Obesity, hyperglycemia, and albuminuria (822±365 vs. 28±8 µg/day) are evident in 18 week old db/db compared to db/m (lean littermate control) mice. Our goal was to determine the blood pressure phenotype of the db/db mouse. Mean arterial blood pressure (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 mm Hg, respectively. The circadian BP profile of db/db mice was shifted to the left and exhibited a significant reduction in amplitude compared to db/m mice. Heart rate (487±9 vs. 542±7 bpm; P<0.05) and locomotor activity were significantly reduced in db/db compared to db/m mice. We tested the hypothesis that intact afferent arteriolar (AA) responsiveness to increases in renal artery pressure (RAP) and angiotensin (ANG) II sensitivity contribute to normal blood pressure in this diabetic model. AA diameters of in vitro blood perfused juxtamedullary nephrons of db/db (15.7±0.5 µm; n=38) were significantly larger than from db/m (12.5±0.4 µm; n=37) mice. 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 AA was observed in kidneys of db/db (-11±4%), while 10 nM ANG II decreased AA diameter in both groups (-20±4%, db/db, n=12; -26±4%, db/m, 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 the db/db mice independently of elevated BP.
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D. Senador, K. Kanakamedala, M. C. Irigoyen, M. Morris, and K. M. Elased Cardiovascular and autonomic phenotype of db/db diabetic mice Exp Physiol, June 1, 2009; 94(6): 648 - 658. [Abstract] [Full Text] [PDF] |
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