Angiotensin II (ANGII) has profound effects on renal and systemic haemodynamics and renal tubular sodium handling. A pathophysiological role has been proposed for ANGII in causing alterations in renal function in the early stages of human Type 1 (insulin-dependent) diabetes mellitus (IDDM). The studies in this thesis have examined the effect on renal function of acute changes in renin-angiotensin system (RAAS) activity induced by low dose ANGII infusion in normal man and patients with IDDM. In preliminary studies the effects of low dose ANGII infusion on whole kidney renal fucntion were defined in normal man and in IDDM. The renal haemodynamic response to ANGII was normal in IDDM patients, but whole kidney tubular sodium retention occurred in IDDM in parallel with a reduced suppression of plasma renin activity after dietary sodium loading compared to control subjects. The utility of lithium clearance as an indirect marker of tubular sodium handling was then assessed. Several problems in interpreting renal haemodynamic data after lithium pretreatment were identified in normal man and in IDDM, but supplementary studies indicated that lithium clearance remains of value as a marker of tubular sodium handling in IDDM. The data indicate that enhanced proximal tubular reabsorption of sodium is associated with a blunted proximal antinatriuretic response to ANGII infusion in IDDM, the severity of this abnormality correlating with the level of chronic glycaemic control. The urinary concentrating response to ANGII infusion is also abnormal inn IDDM. In separate studies insulin did not affect lithium clearance or interact intrarenally with angiotensin II; insulin treatment could not therefore itself account for the abnormal proximal tubular function found in the diabetic subjects. These results support the hypothesis that increased renal proximal tubular retention of sodium in stable uncomplicated Type 1 diabetes is an acquired functional defect, related to the severity of the diabetic metabolic abnormality.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:649849 |
| Date | January 1993 |
| Creators | Eadington, David William |
| Publisher | University of Edinburgh |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/1842/19711 |
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