Cerebrospinal Fluid Angiotensin II Immunoreactivity Is Not Derived from the Plasma

To elucidate whether the presence of angiotensin II immunoreactivity (ANG II-ir) in the cerebrospinal fluid (CSF) of the dog is in part due to passage of the peptide across the CSF-blood-brain barrier, [IIe] angiotensin II (ANG II) was infused Intravenously for 7 days in conscious, trained dogs at a rate of 10 μg/kg/day. Mean arterial pressure (MAP) and heart rate were monitored each day, and samples of arterial blood and CSF (with a catheter secured into the cisterna magna) were drawn at regular intervals for determination of catecholamine levels, ANG II-ir, and electrolyte levels. Within 2 days after ANG II infusion, MAP stabilized at 35 ± 1 mm Hg (mean ± SE, p < 0.001) above control values. The hypertension was associated with bradycardia, suppressed plasma renin activity, and a fall in both plasma and CSF Na+ concentrations. These changes coincided with a considerable and sustained decrease in the levels of plasma and CSF norepinephrine. On the other hand, levels of epinephrine and K in the two compartments remained unchanged. Although concentration of ANG II-ir in plasma was augmented markedly (368% above control values, p < 0.001), ANG II-ir in the CSF remained within the low values measured in the control period. We conclude that ANG II-ir in the CSF of the cisterna magna of the dog does not originate from and is not related to the concentration of the peptide in the plasma, even after considering a possible pressuredependent increase in the permeability of the blood-brain barrier. These data provide further evidence that CSF ANG II-ir may be synthesized in brain tissue and may either be released or diffuse into the extracellular fluid contained in the brain ventricles.