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Biomedical subjects

P Schelling

Publications and source records attributed to P Schelling.

At least 37 records · Page 2Linked to original sources
PubMed1983

Regulation of angiotensinogen in cerebrospinal fluid and plasma of rats.

The origin and regulation of angiotensinogen in cerebrospinal fluid (CSF) was investigated in rats by measuring renin substrate in plasma and CSF under different experimental conditions. Nephrectomy (NX) increased the circulating and the central angiotensinogen levels. There was no correlation between the individual values of plasma and CSF. Adrenalectomy (ADX) diminished and hydrocortisone treatment augmented the angiotensinogen levels in plasma and CSF. The combination of ADX and NX caused a dissociation between peripheral and central angiotensinogen, since the values were elevated in plasma but unchanged in CSF. After the application of the converting-enzyme inhibitor captopril a significant decrease of angiotensinogen was observed in plasma only. A specific radioimmunoassay for renin substrate of rat plasma also recognized CSF angiotensinogen. There was a linear correlation between the CSF substrate levels obtained by direct and indirect measurement. In conclusion, CSF angiotensinogen appears to be immunologically similar to the plasma molecule. The angiotensinogen levels in CSF and plasma may be affected in parallel but can nevertheless be dissociated from each other.

Adrenalectomy↗
PubMed1983

Regulation of angiotensinogen in the central nervous system.

Several interventions known to alter plasma renin substrate in rats such as nephrectomy (NX), adrenalectomy (ADX) and glucocorticoid treatment changed the angiotensinogen content in the cerebrospinal fluid (CSF) in the same direction. However, peripheral and central angiotensinogen could be dissociated from each other by ADX and NX in combination, as well as by chronic converting enzyme blockade. The regulation of brain angiotensinogen was further investigated in stroke-prone spontaneously hypertensive rats (SHR-sp) in comparison with normotensive Wistar Kyoto (WKY) rats. The angiotensinogen levels of the anterior hypothalamus and of the septal area showed strain and age-related differences. Chronic converting enzyme blockade, which kept SHR-sp normotensive, stimulated angiotensinogen in the anterior hypothalamus of both SHR-sp and WKY rats, but suppressed plasma renin substrate. A specific radioimmunoassay (RIA) for renin substrate of rat plasma also recognized the CSF angiotensinogen, and a linear correlation existed between direct and indirect measurements. In conclusion, angiotensinogen in the central nervous system appears to be immunologically similar to plasma angiotensinogen. Its regulation is not directly related, however, to circulating renin substrate, although adrenal steroids stimulate both central and peripheral angiotensinogen. A differential regulation of angiotensinogen in the brain of SHR-sp as compared to WKY is evident and could be linked to blood pressure control.

Aging↗
PubMed1982

Angiotensin-converting enzyme blockade by Captopril changes angiotensin II receptors and angiotensinogen concentrations in the brain of SHR-sp and WKY rats.

Angiotensin II-sensitive neurons in the brain of spontaneously hypertensive rats (SHR-sp) and of Wistar Kyoto rats (WKY) treated with the angiotensin-converting enzyme inhibitor Captopril were investigated for possible differences at receptor sites. Furthermore, the concentrations of angiotensinogen and renin were measured in different brain regions of these animals by biochemical assay. The higher receptor sensitivity of septal neurons to angiotensin II which existed in SHR-sp as compared to WKY was diminished by Captopril. Angiotensinogen concentrations were lower in the anterior hypothalamus but not in the septum of SHR-sp as compared to WKY. Captopril increased the level in both strains. Renin concentrations did not differ in SHR-sp and WKY. Chronic treatment with Captopril induced an increase of about 20% in septum and hypothalamic regions of SHR-sp and WKY rats. Whether these changes are causally linked to the hypertension in SHR-sp remains to be investigated.

Acetylcholine↗
PubMed1982

Increased sensitivity of neurons to angiotensin II in SHR as compared to WKY rats.

Angiotensin II (ANG II)-sensitive septal neurons in the brain of stroke-prone spontaneously hypertensive rats (SHR-sp) and of normotensive Wistar-Kyoto rats (WKY) were investigated for possible differences at receptor sites. ANG II, the competitive ANG II-antagonist saralasin, and acetylcholine (ACh), were applied microiontophoretically onto neurons of the lateral septal area. ANG II-evoked neuronal firing which was specifically inhibited by saralasin occurred at a significant lower threshold in SHR-sp (23%) and showed an extended postactivity (340%) as compared to the age-matched WKY controls. In contrast, the activity due to ACh remained similar in both strains.

Acetylcholine↗
PubMed1982

A micromethod for the measurement of renin in brain nuclei: its application in spontaneously hypertensive rats.

The aim of this study was to develop a method for the measurement of renin activity in small tissue samples obtained from rat brains by the micropunch technique and to investigate the activity of brain renin in spontaneously hypertensive rats. The assay satisfied sensitive and specificity requirements. Angiotensin I was generated at a pH of 6.0; complete recovery of angiotensin I and kinetic studies supported the specificity of the method. Angiotensinase and cathepsin D-like acid protease activity were measured in parallel with renin. Renin was present in all brain regions studied and decreased with the age of the animals. An increased activity of renin was measured in several nuclei of the brain stem and in the neurohypophysis of young hypertensive rats when compared with age-matched normotensive control animals. These differences disappeared in older rats. There was a dissociation between renin and cathepsin D-like acid protease activity. No correlation existed between the distribution of renin and angiotensinase activity. The increased renin activity in brain stem nuclei of spontaneously hypertensive animals is in agreement with previous findings that the brain renin-angiotensin system contributes to the maintenance of high blood pressure in these rats.

Aging↗
PubMed1982

Cardiac output distribution during vasopressin infusion or dehydration in conscious dogs.

To better understand the role of arginine vasopressin in cardiovascular regulation, we measured in unanesthetized dogs regional blood flows with radioactive microspheres before and during 1-h vasopressin infusions that increased the vasopressin concentration of plasma by 11 +/- 0.6 pg/ml. Cardiac output measured by an electromagnetic flowmeter decreased by 13%. Blood flows to the skeletal muscle and skin, the areas most affected, decreased by 30.8 and 34.3%, respectively. In the same group of dogs a period of 48-h water restriction increased plasma vasopressin by 6.9 +/- 1.3 pg/ml and reduced cardiac output by 14.4%. Skeletal muscle blood flow decreased by 32.8%, a pattern strikingly similar to that following vasopressin infusion. Obvious differences between vasopressin infusion and dehydration were also noted, in particular in the skin and splanchnic areas. However, the possibility that vasopressin contributed to the cardiovascular adjustments to dehydration must be considered. The use of an antagonist of the vascular effects of vasopressin, [1-deaminopenicillamine, 2-(O-methyl)tyrosine]arginine-vasopressin ([dPTyr(Me)]AVP), did not permit us to clarify this issue, because this analogue given alone exerted pronounced systemic and regional cardiovascular effects that resembled those of vasopressin.

Animals↗
PubMed1980

Effects of angiotensin II and of an angiotensin II receptor antagonist on simian virus 40-induced tumor growth in vivo.

The effects of angiotensin II and of the competitive angiotensin II receptor antagonist saralasin on in vivo tumor growth were investigated in hamsters. Angiotensin II strongly inhibited tumor growth while saralasin stimulated it, though the high dose used had partial agonistic angiotensin II-like actions. Lower doses of saralasin were without significant effect on tumor weights.

Angiotensin II↗
PubMed1980

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.

From the in vitro and in vivo measurements of the components of the renin-angiotensin system (RAS) in the cerebrospinal fluid (CSF) of rats and dogs, it was concluded that angiotension II (ANG II) is not generated within the CSF in significant amounts, since renin was found to be unmeasurable in CSF under most circumstances. The specific concentrations of angiotensinogen and of converting enzyme (CE) were high. Angiotensin I (ANG I) concentrations were low in CSF, while ANG II levels were comparable to those measured in plasma under control conditions. Neither ANG I nor ANG II penetrated from the blood into the brain ventricles of rats, provided that no unrealistically high doses of ANG II were administered intravenously. This holds true even if high blood pressure increases were induced by intravenous ANG II infusion in deoxycorticosterone acetate (DOCA) and salt-treated rats. However, increased ANG II concentrations were measured in CSF perfusate, when the blood-brain barrier (BBB) was opened by the intracarotid injection of a hyperosmolar urea solution. The brain ventricular perfusion of increasing concentrations of ANG II revealed constant recovery of less than 40%. CSF did not contain angiotensinase activity, but ANG II degradation was high in some periventricular regions. ANG II, the ANG II antagonist saralasin, and the CE inhibitor captopril, respectively, escaped from CSF into circulation when high doses of these substances were applied intraventricularly. We conclude that ANG II in the CSF does not originate from and is not related to plasma ANG II. It is probably not generated within the CSF. ANG II may be synthetized in the brain tissue and be released into the brain ventricles where its rapid degradation occurs in contact with circumventricular structures.

Angiotensin I↗
PubMed1979

Effects of angiotensin II and angiotensin II antagonist saralasin on cell growth and renin in 3T3 and SV3T3 cells.

Components of the renin-angiotensin system were studied in established cell culture lines of 3T3 and SV3T3 mouse fibroblasts. The renin content in 3T3 cells was significantly higher than in virus-transformed SV3T3 cells. With time after infection, renin decreased in Simian virus 40 transformed cells, while it increased steadily in mock-infected 3T3 cells. In contrast to renin, angiotensinase activity was higher in SV3T3 cells. Angiotensin II stimulated cell proliferation in 3T3 mouse fibroblasts and decreased their renin content in a dose-related manner. In contrast, saralasin, an angiotensin receptor antagonist, inhibited cell growth in 3T3 and SV3T3 cells and caused an increase of cellular renin concentration. The angiotensin fragments angiotensin (2-8) heptapeptide and angiotensin (4-8) pentapeptide had no effect on cell growth. A significant negative correlation was found between cell proliferation and renin levels in 3T3 and SV3T3 cells irrespective of the treatment. Our results indicate (1) that angiotensin II may be involved in cell growth regulation, (2) that a negative feedback exist between angiotensin II added and intracellular renin content, and (3) that virus infection causes a decrease in intracellular renin synthesis, while non-specific angiotensinase activity is increased under this condition.

Angiotensin II↗
PubMed1978

In vivo enzyme activity of purified human brain renin.

Cerebrospinal fluid (CSF) of rats contains high angiotensinogen concentrations. When 3500-fold purified renin from human brain was injected into the brain ventricles of rats, angiotensin I concentrations increased from undetectable levels to 147.9 +/- 18.8 fMol per ml CSF. In parallel, mean arterial blood pressure increased from 93 +/- 2.4 mm Hg to 107 +/- 3.7 mm Hg. The increase in blood pressure could be abolished by intraventricular administration of saralasin, a blocker of angiotensin II receptors. Intraventricular injection of cathepsin D had no effect on arterial blood pressure and the agiotensin I concentration in CSF remained below detection limits of the radioimmunoassay. We conclude that brain renin acts on endogenous brain angiotensinogen under physioloical in vivo conditions to form angiotensin I. The latter is converted to angiotensin II and leads to biological effects, i.e. increase of blood pressure.

Angiotensin I↗
PubMed1978

Inhibition of drinking in water-deprived rats by combined central angiotensin II and cholinergic receptor blockade.

The effect of blockade of central angiotensin II (AII) receptors and cholinergic receptors on thirst induced by water deprivation was studied in Sprague-Dawley rats and rats with hereditary hypothalamic diabetes insipidus (DI). Neither central AII nor cholinergic blockade alone affected drinking. Antagonism of both receptors simultaneously, however, significantly inhibited water intake of both Sprague-Dawley and DI rats. This inhibitory effect was not observed in water-deprived, nephrectomized rats. The combined antagonism on water intake was specific, since milk intake in hungry rats was not affected by simultaneous AII and cholinergic blockade. Isorenin concentrations in brain tissue were at control levels in water-deprived, nephrectomized, and non-nephrectomized Sprague-Dawley rats but were increased in water-deprived DI rats. The results suggest that angiotensin and cholinergic receptors in the brain have a physiological role in thirst. Thirst is maintained when either receptor is intact, but reduced when both receptors are inhibited by antagonists. They are independently capable of maintaining thirst.

Animals↗
PubMed1976

Iso-renin of extrarenal origin. "The tissue angiotensinogenase systems".

Enzymes, similar to kidney renin, are present in extrarenal tissue of most mammals; they hydrolyze angiotensinogen to form angiotensin I. We suggest that these enzymes be called angiotensinogenases. Angiotensinogenase concentrations in extrarenal tissue can exceed those in the kidney. The enzyme has been obtained in pure crystalline form. Angiotensinogenases are part of a complex enzyme system which leads to local production of angiotensin. Results indicating a biologic role of the angiotensinogenase system in brain, adrenal gland, uterus and tissue culture are discussed.

Adrenal Glands↗
PubMed1976

Tissue iso-renins.

1. Several extrarenal tissues contain enzymes which are similar to kidney renin: they hydrolyse angiotensinogen to form angiotensin I; they have characteristic substrate specificity; the physicochemical properties of kidney renin and of extrarenal tissue iso-renin are similar. 2. Results indicate that tissue iso-renins are part of a complex enzyme system with mainly local function. A possible biological role has been demonstrated in brain, adrenal gland and tissue culture.

Adrenal Glands↗