Under normotensive conditions, the progressive loss of renal function in diabetes
mellitus is very slow. Since hypertension accelerates many forms of renal disease, we
assessed the progression of nephropathy in Streptozotocin-induced type 1 diabetes
mellitus under renin-mediated hypertension condition. We investigated the diabetic “salt
paradox” as a modifiable susceptibility factor for renal damage. Since hyperfiltration
occurs in early diabetes, the reduction of glomerular filtration rate due to an increased salt
intake could be mediated by increased tubuloglomerular feedback sensitivity. We
compared intact-hypertensive versus diabetic-hypertensive Long-Evans rats under normal
and increased salt intake, 1 and 2.5% by weight of food eaten, respectively. Weekly 24-h
blood pressure records were acquired by telemetry during the six months of the
experiment. Target mean blood glucose of ~ 25 mmol/L was maintained by suboptimal
insulin implants. Systolic blood pressure increased after induction of hypertension but
was not affected by diabetes or increased salt intake, either alone or together.
Autoregulation was highly efficient in both intact and diabetic rats. Nephropathy was
scored by histology in the clipped and non-clipped kidneys at the end of the protocol. The
non-clipped kidney, which was exposed to hypertension, showed a linear
pressure-dependent glomerular injury in both intact and diabetic rats. The best fit line
describing the linear relationship between pressure load and injury was shifted toward
lower blood pressure in diabetic rats. Over the time course of our experiments, injury was
entirely pressure dependent in intact and diabetic rats. Diabetes mellitus increased the
susceptibility of the kidney to injury, but independent of blood pressure. Increased salt
intake affected neither blood pressure nor renal susceptibility to hypertensive injury. / Graduate
| Identifer | oai:union.ndltd.org:uvic.ca/oai:dspace.library.uvic.ca:1828/3403 |
| Date | 14 July 2011 |
| Creators | Sima, Carmen Aurelia |
| Contributors | Cupples, William Angus |
| Source Sets | University of Victoria |
| Language | English, English |
| Detected Language | English |
| Type | Thesis |
| Rights | Available to the World Wide Web |
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