Effects of chronic hypoxia on renal renin gene expression in rats

Background, The effects of hypoxia on renin secretion and renin gene expres sion have been controversial. In recent studies, we have demonstrated that acute hypoxia of 6 h duration caused a marked stimulation of renin secretio n 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 slee p-apnoea syndrome. For this reason, we were interested in the more chronic effects of hypoxia on renal renin gene expression and its possible regulati on. Methods. Male rats were exposed to chronic normobaric hypoxia (10%, O-2) fo r 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. Re nal renin, endothelin-1 and endothelin-3 gene expression were quantitated u sing RNAase protection assays. Results. During chronic hypoxia, haematocrit increased to 72+/-2%, and righ t ventricular pressure increased by a mean of 26 mmHg. Renal renin gene exp ression was halved during 4 weeks of chronic hypoxia. This decrease was rev ersed 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 increas ing renal endothelin-1 gene expression (to 173% of baseline values) after 4 weeks of hypoxia. Systolic blood pressure increased moderately during 4 we eks of chronic hypoxia from 129+/-2 to 150+/-4 mmHg. This blood pressure in crease was higher in rats treated for 4 weeks with an endothelin receptor a ntagonist (196+/-11 mmHg). Conclusions. Chronic hypoxia (in contrast to acute hypoxia) suppresses rena l renin gene expression. This inhibition presumably is mediated by endothel ins.