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(Hypertension. 2001;37:1375.)
© 2001 American Heart Association, Inc.

Scientific Contributions

Neural Mechanisms Subserving Central Angiotensinergic Influences on Plasma Renin in Sheep

M. J. McKinley; M. I. McBurnie; M. L. Mathai

From Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Victoria, Australia.

Correspondence to Dr M.J. McKinley, Howard Florey Institute, University of Melbourne 3010, Victoria, Australia. E-mail mmck{at}hfi.unimelb.edu.au

Abstract—The mechanisms and brain regions subserving the suppression of plasma renin concentration caused by intracerebroventricular (ICV) infusion of angiotensin II were studied in sodium-depleted sheep. Infusion of angiotensin II (3 µg/h for 1 hour) into the lateral ventricle reduced plasma renin from 4.3±0.4 to 1.6±0.2 pmol angiotensin I/mL per hour at 1 hour after the commencement of infusion. This change persisted for at least another 90 minutes and was blocked by concomitant ICV infusion of the AT₁ antagonist losartan (1 mg/h). Arterial pressure did not change, but plasma vasopressin secretion was increased. ICV infusion of losartan (1 mg/h) significantly increased plasma renin in sodium-depleted sheep. The reduction of plasma renin concentration in response to either ICV angiotensin II or hypertonic NaCl (0.75 mol/L at 1 mL/h) and the increase in response to ICV losartan was prevented in sheep in which the lamina terminalis of the brain had been ablated. Lesions in the median eminence (MEL), which blocked the increased plasma vasopressin levels, did not prevent suppression of plasma renin in response to ICV angiotensin II. However, bilateral renal denervation largely blocked this inhibition of plasma renin concentration but not the increased plasma renin resulting from ICV infusion of losartan in sodium-depleted sheep. The results show that AT₁ receptors, probably located in the lamina terminalis, mediate a central inhibitory influence of angiotensin II on renin secretion. This inhibition of renin release is probably due to a reduction in activity of renal sympathetic nerves innervating the juxtaglomerular apparatus of the kidney.

Key Words: angiotensin • renin • receptors, angiotensin • renal nerves