Independence of the central nervous and the peripheral renin-angiotensin systems in the dog.

Abstract

SUMMARY What regulates the activity of the central nervous renln-angiotensln system is not known. To define whether control of this central system is linked to that in the periphery, simultaneous blood and cerebrospinal fluid (CSF) samples for measurement of immunoreactive angiotensin II were drawn from anesthetized dogs during hemorrhage, furosemide-induced Tolume depletion, insulln-hypoglycemia, betaadrenergic blockade and saline infusion. Despite rigorous increments or decrements in plasma immunoreactive angiotensin II, CSF levels remained stable. Since immunoreactive angiotensin II in dog CSF is claimed to be mainly the heptapeptide des-Asp'-angiotensln II (angiotensin III), the possibility that the level of this peptide within CSF simply reflects plasma concentrations was assessed by infusing angiotensin III (2.5 and 25 ng/kg/min intravenously, each for 60 minutes) and monitoring plasma and CSF peptide levels. Whereas plasma immunoreactive angiotensin II levels increased appropriately across the infusions, no change in CSF levels was observed. These studies indicate that angiotensiii III does not cross the blood-CSF barrier, at least in the short term. 18 There is evidence that the reninangiotensin system within the central nervous system might be involved in the pathogenesis of some forms of hypertension in animals 1117 and in man. 18While the physiological and pathophysiological importance of this system is being vigorously researched, the question of what regulates its activity has received less attention. The current study therefore set out to determine whether there was any parallelism in the control of the peripheral and the central nervous renin-angiotensin systems. Further, since immunoreactive angiotensin II in dog cerebrospinal fluid (CSF) may in fact consist largely of the heptapeptide des-Asp^angiotensin II, 19 the possibility that this peptide within CSF might simply reflect concurrent plasma levels was explored. 228 Materials and MethodsAll experiments were carried out in male mongrel dogs weighing 19.1-35 kg. Each dog was used on only one occasion. Fluid and dietary intake were not restricted before the experimental day. Anesthesia was induced with sodium pentobarbital (30 mg/kg I.V.) and maintained with additional amounts of the barbiturate as required (7.5 mg/kg every 2 hours in most cases). Two cannulae were inserted into peripheral leg veins, one for infusion, the other for blood withdrawal. With the dog's head held in flexion, a 17-gauge needle (Portex Epidural Minipacks) was introduced into the cisternal space under strictly sterile conditions. Clear CSF, uncontaminated by blood, could be aspirated rapidly, and in many cases streamed under pressure from the cisternal needle. In the few instances that blood-contaminated CSF was obtained, the dog was excluded from the study. A 45-minute stabilization period prior to blood and CSF sampling was observed after insertion of the cisternal needle. As a routine, two "basal" CSF and blood samples were obtained for analysis before the experimenta...

Components of the Renin-Angiotensin System in the Cerebrospinal Fluid of Rats and Dogs with Special Consideration of the Origin and the Fate of Angiotensin II

“…The same or somewhat lower ANG II levels were re ported for CSF of men [54,59] and sheep [1). Depending upon the RIA procedure, CSF ANG II levels of dogs were found by others to be undetectable or within the range re ported here [50], while even higher amounts were measured in a further study [33]. Discrepancies in immunoreactive ANG II levels could be related in part to the specificity of the antibody used.…”

Effects of water deprivation on immunoreactive angiotensin II levels in plasma, cerebroventricular perfusate and hypothalamus of the rat

“…Intravenous infusion of All does not induce an increase in immunoreactive All in cerebrospinal fluid of the dog (Nicholls 1979) or ventricular perfusate of the rat ). These observations mean that angiotensin cannot easily cross the blood-brain barrier.…”