Vasoregulatory hormones and the hyperfiltration of diabetes

Abstract

The role of renal vasoregulatory hormones in the hyperfiltration of early insulin-dependent diabetes mellitus (IDDM) was studied by micropuncture methods in rats with streptozotocin-induced diabetes. Seven to ten days after streptozotocin injection, untreated diabetic rats had elevated glomerular filtration rate (GFR) and single-nephron glomerular filtration rate (SNGFR), compared with normal euvolemic rats. Infusion of indomethacin (5 mg/kg) markedly reduced urinary and proximal tubular fluid prostaglandin E2 (PGE2), but GFR and SNGFR did not change. In a second group, intrarenal infusion of aprotinin (1,000 kallikrein inhibitor units.min-1.kg-1) to inhibit kallikrein also had no effect on GFR or SNGFR. In a third group, intrarenal infusion of angiotensin II (ANG II, 0.1 microgram.min-1.kg-1) reduced GFR, renal plasma flow (RPF), SNGFR, and glomerular plasma flow rate (QA) to values close to those in normal euvolemic rats. Single-nephron filtration fraction rose significantly with ANG II, but glomerular pressure (PG) was unaltered. Tubular fluid PGE2 increased in response to ANG II. Saralasin infusion following ANG II returned GFR, RPF, SNGFR, and QA to supernormal levels, and PG fell. In chronically salt-loaded normal rats, the responses to intrarenal ANG II and saralasin were similar to those observed in the diabetic rats. We conclude that hyperfiltration in early IDDM is not dependent on intact renal PGE2 or bradykinin synthesis. The results with ANG II infusion indicate that pre- and postglomerular and glomerular contractile cells of the diabetic kidney are able to constrict in response to this hormone.

Immunohistochemical and functional correlations of renal cyclooxygenase-2 in experimental diabetes

“…A decrease in RPF has been observed previously by some investigators in diabetic rats treated with nonselective COX inhibitors (7). Considering approximately 50% suppression of urinary PGE 2 excretion in response to isoform-selective inhibitors in the present studies, as compared with 70-90% achieved by nonselective inhibitors (39,42,43), this finding is not surprising. It appears that concomitant inhibition of both isoforms is necessary to elicit significant renal vasoconstriction in diabetic rats.…”

Sorbinil does not prevent hyperfiltration, elevated ultrafiltration pressure and albuminuria in streptozotocin-diabetic rats

“…If any clinical conclusions are to be drawn from experimental studies, the rats used in such a study should have a well-defined state of diabetes [5,14]. The rats in this study were under daily supervision with regard to blood glucose control, insulin administration and body weight.…”

Role of COX-2 in the Enhanced Vasoconstrictor Effect of Arachidonic Acid in the Diabetic Rat Kidney

“…Vasodilator responses to endothelium-dependent agents are reduced, 1,2 whereas responses to vasoconstrictor agents are decreased, increased, or unchanged. [3][4][5][6][7][8] In studies conducted more than a decade ago, we observed that vasoconstrictor responses to angiotensin II and vasopressin in the isolated perfused kidney obtained from diabetic rats were impaired compared with those in kidneys from age-matched nondiabetic rats, whereas no differences in responses to phenylephrine were noted. 5 In contrast, we found that the vasoconstrictor responses to arachidonic acid (AA) in the perfused kidney of diabetic rats were markedly enhanced.…”