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

The adrenal cortex and essential hypertension.

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Adrenal Cortex↗

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↗

PubMed1976

Effect of intraventricular perfusion of angiotensin II in conscious normal rats and in rats with hereditary hypothalamic diabetes insipidus.

1. Artificial cerebrospinal fluid was perfused through the cerebral ventricles of conscious rats. A basal secretion rate of 16 +/- 3 X 10(-15) mol of immunoreactive angiotensin II/min was calculated for intact rats. 2. Most of the immunoreactive angiotensin II consisted probably of the heptapeptide or pentapeptide angiotensin II fragments. 3. The pressor response to intraventricular perfusions of angiotensin II were normal in Long-Evans rats, virtually absent in rats homozygous for hereditary hypothalamic diabetes insipidus, irrespective of whether they were injected with vasopressin tannate or not, and intermediate in rats heterozygous for hypothalamic diabetes insipidus. 4. The results suggest that the pressor response to intraventricular angiotensin II is related to the release of vasopressin.

Angiotensin II↗

PubMed1976

Impermeability of the blood-cerebrospinal fluid barrier for angiotensin II in 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.

Angiotensin II↗

PubMed1976

Pressor action of centrally perfused angiotensin II in rats with hereditary hypothalamic diabetes insipidus.

A method was devised for the perfusion of the cerebral ventricles in conscious rats. Using this method a basal secretion rate of 15 +/- 3 pg of immunoreactive angiotensin II per min was calculated. This material was suggested to be of extrarenal origin. In comparison to findings in normal Long-Evans rats, pressor responses to intraventricular perfusions of angiotensin II were reduced in rats heterozygous for hypothalamic diabetes insipidus and virtually absent in rats homozygous for the hypothalamic deficiency whether they were treated with vasopressin or not. The pressor response to intraventricular angiotensin II is suggested to be related to the release of vasopressin.

Angiotensin II↗

PubMed1976

Central pressor actions of angiotensin II.

Involvement of the area postrema in experimental hypertension has been investigated. Ablation of the rear apex of the fourth brain ventricle (=the region of the area postrema) elevated blood pressure, heart rate and plasma angiotensin II level. The same characteristic changes were seen in the two kidney Goldblatt rat model of hypertension. A possible involvement of the area postrema in this model of hypertension is discussed. Intraventricular perfusion of angiotensin II elevated blood pressure without a significant change in heart rates. This pressor response appeared to be dependent on release of antidiuretic hormone. The results are discussed in relation to the intrinsic brain angiotensinogenase system.

Angiotensin II↗

PubMed1975

The intrinsic brain iso-renin--angiotensin system in the rat: its possible role in central mechanisms of blood pressure regulation.

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 II is elevated in the cerebrospinal fluid of spontaneously hypertensive rats. 6. An intraventricular perfusion of the angiotensin II receptor-blocking agent P 113 decreases blood pressure in spontaneously hypertensive rats.

Angiotensin II↗

PubMed1975

The renin-angiotensin system in rats made hypertensive by ligation of the kidney poles (38584).

The renin-angiotensin system was studied in experimental renal hypertension produced by ligation of the poles of the left kidney followed by contralateral nephrectomy. Plasma renin concentration of renin substrate was lower and that of angiotensin I converting enzyme was higher in hypertensive animals. The juxtaglomerular index decreased in the medial zone of the kidney, while heavily granulated areas appeared in the poles. Ligated kidneys of rats that remained normotensive showed juxtaglomerular indices intermediate between the control and the hypertensive rats. Differences in renal renin content between the groups correspond to those for the juxtaglomerular index, but were smaller. No differences between the experimental groups were observed in iso-renin content in the brain; however in all animals with ligated kidney poles, hypertensive or normotensive, there was a tendency for iso-renin in the adrenals, left ventricular myocardium, and especially aorta to be lower than in controls.

Adrenal Glands↗

PubMed1975

Proceedings: Differential pressor responses to centrally administered angiotensin II (A II) in conscious rats, homozygous and heterozygous for hypothalamic diabetes insipidus.

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Angiotensin II↗

PubMed1975

The renin and iso-renin-angiotensin system in rats with experimental pitutary tumors (38585).

Renin, iso-renin, angiotensin I. angiotensin-converting enzyme, and angiotensinases were measured in plasma and in various extrarenal tissues of rats. Despite complete suppression of plasma renin in rats bearing pituitary tumors iso-renin and all other components of the renin-angiotensin system were found to be at or above control concentrations. The results strongly suggest that there is local synthesis of iso-renin in extrarenal tissues.

Adrenal Glands↗