Nephrol Dial Transplant (2000) 15: 11-15
© 2000 European Renal Association-European Dialysis and Transplant Association
Effects of chronic hypoxia on renal renin gene expression in rats
Klinik und Poliklinik für Innere Medizin II, Klinikum der Universität Regensburg, Regensburg, Germany
Correspondence and offprint requests to: Dr Bernhard K. Krämer, Klinik und Poliklinik für Innere Medizin II, Klinikum der Universität Regensburg, D-93042 Regensburg, Germany.
Background. The effects of hypoxia on renin secretion and renin gene expression have been controversial. In recent studies, we have demonstrated that acute hypoxia of 6 h duration caused a marked stimulation of renin secretion and renal renin gene expression. This hypoxia-induced stimulation of the renin–angiotensin system might contribute, for example, to the progression of chronic renal failure and to the development of hypertension in the sleep-apnoea syndrome. For this reason, we were interested in the more chronic effects of hypoxia on renal renin gene expression and its possible regulation.
Methods. Male rats were exposed to chronic normobaric hypoxia (10% O2) for 2 and 4 weeks. Additional groups of rats were treated with an endothelin ETA receptor antagonist, LU135252, or a NO donor, molsidomine, respectively. Systolic blood pressure and right ventricular pressures were measured. Renal renin, endothelin-1 and endothelin-3 gene expression were quantitated using RNAase protection assays.
Results. During chronic hypoxia, haematocrit increased to 72±2%, and right ventricular pressure increased by a mean of 26 mmHg. Renal renin gene expression was halved during 4 weeks of chronic hypoxia. This decrease was reversed by endothelin receptor blockade (105 or 140% of baseline values after treatment for weeks 3–4 or 1–4). Furthermore, there was a trend of increasing renal endothelin-1 gene expression (to 173% of baseline values) after 4 weeks of hypoxia. Systolic blood pressure increased moderately during 4 weeks of chronic hypoxia from 129±2 to 150±4 mmHg. This blood pressure increase was higher in rats treated for 4 weeks with an endothelin receptor antagonist (196±11 mmHg).
Conclusions. Chronic hypoxia (in contrast to acute hypoxia) suppresses renal renin gene expression. This inhibition presumably is mediated by endothelins.
Keywords: chronic hypoxia; endothelin; nitric oxide; renal renin expression
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