Extrarenal renin-angiotensin systems are unable to maintain blood pressure in sheep

1. The present study was designed to assess the participation of extrarenal tissue renin-angiotensin systems (RAS) in pressure homeostasis in sheep. 2. The effect of the administration of an angiotensin II type 1 receptor antagonist (losartan; 30 mg/kg, i.v.) on mean arterial blood pressure (MABP) was investigated in eight intact (controls) and 10 binephrectomized sheep haemodialysed every 2 days for 10 days. 3. In control sheep, losartan decreased blood pressure and this decrease was significantly more marked after furosemide-induced water and salt depletion. After nephrectomy and throughout the anephric period, losartan lost its hypotensive effect, while the plasma renin concentration fell to undetectable levels. Baseline MABP became significantly lower than at the beginning of the anephric period after 7 days. The inability to maintain blood pressure after several volume-depleting haemodialysis sessions proved that an efficient system for blood pressure regulation was lacking after nephrectomy. 4. Renin gene expression measured by reverse transcription-polymerase chain reaction was found in liver, adrenal and arterial wall tissue. Neither nephrectomy nor sodium depletion enhanced this tissue renin gene expression. 5. In conclusion, the present work allows us to exclude an active role of extrarenal RAS in the maintenance of blood pressure. In addition, haemodialysis technology in nephrectomized sheep can be used as a good model for the study of extrarenal control of blood pressure.