No abstract

1.Angiotensin is produced by the intrinsic isorenin-angiotensin system.2. Angiotensin is secreted into the cerebrospinal fluid of nephrectomized rats. 3. Angiotensin in cerebrospinal fluid elevates systemic blood pressure. 4. Rats with hereditary diabetes insipidus are virtually non-responsive to intraventricular angiotensin. 5. Angiotensin I1 is devated in the cerebrospinal fluid of spontaneously hypertensive rats.6. An intraventricular perfusion of the angiotensin I1 receptor-blocking agent P 113 decreases blood pressure in spontaneously hypertensive rats.Key words : angiotensin analogue, blood-brain barrier, central blood pressure regulation, cerebrospinal fluid, diabetes insipidus rats, intrinsic brain iso-renin-angiotensin system, spontaneously hypertensive rats.

1. Anaesthetized, nephrectomized rats were infused intravenously with unlabelled angiotensin II (AII) or with [3H]angiotensin II (3H-labelled AII). The brain ventricular system was perfused with artificial cerebrospinal fluid. The perfusate was collected from the cisterna magna and analysed for AII by radioimmunological and biochemical methods. 2. No increase of immunoreactive AII in cerebrospinal fluid could be shown during intravenous infusion of AII. 3. During intravenous infusions of 3H-labelled AII at pressor doses small amounts of radioactivity were found in cerebrospinal fluid perfusate. 4. The radioactivity of cerebrospinal fluid outflow could not be related to AII.

SUMMARYIn conscious spontaneously hypertensive rats, intracerebroTentricular injection of captopril (2 rag/kg) resulted in a rapid hypotenshe response that lasted several hours. The same dose given by Intracerebroventricular injection had no significant effect on blood pressure (BP) of normotensive Wistar-Kyoto (WK) rats over 7 hours. There was no significant change in BP of conscious spontaneously hypertensive rats (SHR) in response to Intracerebroventricular injection of vehicle and only a transitory fall in BP in response to intravenous injection of captopril (2 mg/kg). There was no significant differences between plasma renin activity (PRA) of conscious norrootenslve WKY rats and the PRA of SHR. These results suggest biochemical differences between the brains of SHR and normotensive WKY control rats. These differences could involve the brain renin-angiotensin system or other iteuropeptides. renin-angiotensin system in the brain has been the subject of some controversy.

Injection of angiotensin II (AII) into the cerebral ventricles at doses as low as 1 pmol h-1 results in a marked stimulation of salt and water ingestion in the rat. Evidence that AII is produced in the central nervous system independently of the circulating renin-angiotensin system (RAS) raises the possibility that endogenous brain AII is involved in the physiological regulation of thirst. The role of brain AII in salt appetite is still unclear. Here we confirm that the spontaneously hypertensive rat (SHR), believed to have elevated levels of brain AII, possesses an exaggerated salt appetite compared with its normotensive controls. We also show that this exaggerated salt appetite is reduced by chronic central treatment with the angiotensin-converting enzyme inhibitor, captopril, while that of the normotensive controls is unaffected. Our study suggests that a central neuropeptide, probably AII, is involved in the maintenance of the exaggerated salt appetite in this model of hypertension.