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INCREASED SENSITIVITY TO ENDOTHELIN‐1 IN ISOLATED KREBS‐PERFUSED KIDNEYS OF STREPTOZOTOCIN‐DIABETIC RATS
Author(s) -
Tammesild Paul J.,
Hodgson Wayne C.,
King Roger G.
Publication year - 1992
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1992.tb00448.x
Subject(s) - endocrinology , medicine , kidney , streptozotocin , perfusion , endothelins , endothelin receptor , chemistry , diabetes mellitus , endothelin 1 , receptor
SUMMARY 1. Vascular responses to endothelin‐1 (ET‐1) and noradrenaline (NA) were measured in isolated Krebs'‐perfused kidneys of 2 week old streptozotocin‐diabetic and non‐diabetic rats. 2. Bolus injections of either ET‐1 or NA caused dose‐dependent increases in perfusion pressure. Responses to ET‐1 (10–60 ng/g kidney), but not to NA (0.001–10 μg/g kidney), were significantly potentiated in kidneys of diabetic rats compared with non‐diabetics. 3. Indomethacin significantly attenuated responses to NA (0.3–10 μg/g kidney) in kidneys of both diabetic and non‐diabetic rats. 4. Neither indomethacin (1 μmol/L) nor the cyclo‐oxygenase/lipoxygenase inhibitor BW755C (1 μmol/L) had any significant effect on the log dose‐response curve to ET‐1 in either group of kidneys. 5. Perfusion with N‐nitro‐L‐arginine (NOLA; 10 μmol/L) had no effect on basal perfusion pressures, but potentiated responses to ET‐1 in both groups of kidneys. However, the difference in responses to ET‐1 between kidneys from diabetic and non‐diabetic rats remained significant in the presence of NOLA. 6. ET‐1 responses were inhibited in Ca 2+ ‐free Krebs’ solution (plus 1 mmol/L EGTA). 7. The results of the present study indicate an increased sensitivity to ET‐1 in isolated Krebs'‐perfused kidneys of diabetic rats. Responses to ET‐1 were unaffected by cyclo‐oxygenase and/ or lipoxygenase inhibitors, but were potentiated by an endothelium‐derived relaxing factor (EDRF) synthesis inhibitor.