Angiotensinogen concentration in the cerebrospinal fluid in different experimental conditions in the rat.

Abstract

SUMMARY Angiotensinogen is the most important component of the renin-angiotensin system present in the cerebrospinal fluid (CSF) of the rat. Its physiological significance as well as its origin have not been clearly elucidated. In this experiment we have examined plasma renin activity (PRA) and plasma and CSF angiotensinogen concentration under the following experimental conditions in male rats of the Wistar strain: 1) adrenalectomy (Adx) 4 days prior to sample collection; controls were sham Adx animals; 2) nephrectomy (Nx) 48 hours before blood and CSF collection; controls were sham Nx rats; 3) DOC-salt treatment (Cortexon depot, 50 mg/kg.s.c. twice a week) plus saline to drink was given during 4 weeks; controls were intact rats; 4) DOC-salt plus captopril: captopril (100 mg/kg/ day) in the drinking fluid was added to the treatment of experimental and control animals of Group 3; 5) two-kidney, two clip hypertension: silver clips placed in both renal arteries 8 weeks before samples collection; control: sham-operated rats; 6) water deprivation: rats deprived of water for 5 days; controls: intact rats; 7) peripheral sympathectomy: 6-hydroxydopamine (6-HODA) injected s.c. from birth until 16 weeks of age, adrenodemedullectomy and adrenal denervation performed at 8 weeks; controls were vehicle-injected animals.Determination of angiotensinogen concentration in plasma and CSF was accomplished by incubation of the samples with excess hog renin. The angiotensin I released as well as PRA were evaluated using an specific radioimmunoassay technique. PRA was significantly increased by Adx, captopril treatment, and water deprivation, and was almost suppressed by Nx, DOC-salt, and DOC-salt plus captopril treatment. Plasma angiotensinogen concentration was significantly elevated by Nx and significantly diminished by Adx, DOC-salt, and DOC-salt plus captopril, and captopril treatment. T HE presence of angiotensinogen in the brain and cerebrospinal fluid (CFS) of rabbits, dogs, rats, and humans has been clearly demonstrated. '^ Biochemical analysis has shown a similar molecular weight and electrophoretic mobility for plasma and CSF renin substrate; moreover, the final product released by both prohormones was identical to synthetic angiotensin I (AI) with respect to isoelectric point or pressor response.3 Clear differences between CSF and plasma angiotensinogen were also observed. In this regard, central renin substrate was heterogeneous with respect to isoionic points; the plasma protein presented only one component. In addition, im- munological differences between the central and peripheral renin substrate were also established.5 Although not definitively demonstrated, most of the available information supports a central origin for the angiotensinogen present in the brain and CSF of mammals and humans. Some experimental conditions determine a similar change in peripheral and central prohormone. 6 However, in a previous report 7 we found a clear dissociation between plasma and brain angiotensinogen in DOC-salt-treated hypertensi...

Simvastatin Ameliorates Angiotensin II-Induced Endothelial Dysfunction Through Restoration of Rho-BH4-eNOS-NO Pathway

“…Activation of renin-angiotensin-adolesterone system (RAS) is critical for the pathogenesis of reno-hypertension [20,24]. In our 2k2c model, RAS activation was characterized by a significant increase in plasma Ang II.…”

Nuclear localization of angiotensinogen in astrocytes

“…The most abundant sources of AGT in the brain are astrocytes, which have been reported to constitutively secrete AGT into the extracellular and cerebrospinal fluids (9,35,40). In addition to the AGT-positive astrocytes that are found throughout the brain, AGT is also present in a limited population of neurons in regions of the brain dedicated to cardiovascular control (45).…”

Changes in central and peripheral renin-angiotensin system after furosemide injection.

“…Plasma and CSF angiotensinogen levels were not influenced by furosemide injection, which showed a stimulatory effect on the renin-angiotensin system. Changes in plasma angiotensinogen due to salt restriction or water deprivation remain controversial (Ruiz et al, 1983, Schelling et al, 1983, Genain et al, 1983. Rosset and Vergrat (1971) have shown that in normal human subjects sodium restriction results in a decrease in plasma angiotensinogen and also an increase in PRA, while Chen et al (1983) have reported increased plasma angiotensinogen and significant elevation of the prohormone in some brain regions of rats deprived of water for 72h.…”

“…Since an endogenous brain renin-angiotensin system was proposed by Ganten et al (1971) and Fisher-Ferraro et al (1971), several investigations have been performed in order to clarify its contribution to blood pressure regulation and water-electrolyte balance under physiological and pathological conditions (Fuxe et al, 1976, Schelling et al, 1980. Several studies have tried to elucidate the relationship between the brain and the peripheral renin-angiotensin system by simultaneous measurements of plasma and cerebrospinal fluid (CSF) renin (Brosnihan et al, 1982), angiotensin II (Suzuki et al, 1983) and angiotensinogen (Finkielman et al, 1972, Ruiz et al, 1983, Schelling et al, 1983. Accumulated evidence from such studies has indicated that there may be a close relationship between these two compartments.…”