Abstract
A ROLE for the renin-angiotensin system in the development or maintenance of increased blood pressure of spontaneously hypertensive (SH) rats has not been substantiated. These animals are considered the best model for human essential hypertension. Although there have been reports of unusually high concentrations of renin in the plasma of young SH rats2, their pathophysiological relevance has been questioned3 and, as we report here, high blood pressure is maintained even after nephrectomy. But angiotensin from the brain isorenin–angiotensin system (Iso–RAS) could be involved4,6. All the components of that system have been identified in brain tissue, including the enzyme iso-renin4–6, the substrate, angiotensinogen7, angiotensin I and converting enzyme6,8 which hydrolyses angiotensin I to form the biologically active octapeptide angiotensin II. Angiotensin II is also present in brain tissue6. When it is injected intraventricularly into the brain angiotensin II produces a prolonged increase in blood pressure9. Therefore, if angiotensin II concentrations are increased in the brains of SH rats they could be involved in the hypertensive state independently of angiotensin levels from renal origin in plasma. Using the competitive antagonist Sar-1-Ala-8-angiotensin II (saralasin acetate, P113, Norwich Pharmacal) in SH and nephrectomised SH rats, we have confirmed this possibility.
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PHILLIPS, M., MANN, J., HAEBARA, H. et al. Lowering of hypertension by central saralasin in the absence of plasma renin. Nature 270, 445–447 (1977). https://doi.org/10.1038/270445a0
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DOI: https://doi.org/10.1038/270445a0
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