Vasoregulatory hormones and the hyperfiltration of diabetes.
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.
D000465:Algorithms; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D007611:Aprotinin / Q000494:pharmacology; D001920:Bradykinin / Q000096:biosynthesis / Q000502:physiology*; D003928:Diabetic Nephropathies / Q000503:physiopathology*; D015232:Dinoprostone; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology; D007668:Kidney / Q000098:blood supply*; D008297:Male; D011453:Prostaglandins / Q000096:biosynthesis / Q000502:physiology*; D011458:Prostaglandins E / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains; D012504:Saralasin / Q000494:pharmacology
D011453:Prostaglandins; D011458:Prostaglandins E; D000804:Angiotensin II; D007611:Aprotinin; D012504:Saralasin; D015232:Dinoprostone; D001920:Bradykinin; D007213:Indomethacin