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Biomedical subjects

D Ganten

Publications and source records attributed to D Ganten.

At least 415 records · Page 23Linked to original sources

Oxytocin unlike vasopressin is a stress hormone in the rat.

The functions of oxytocin in the female are thought to be confined to the processes of milk ejection and parturition. In this study the role of oxytocin in the body's response to stressful stimuli has been examined. Physical immobilization of rats and forced swimming caused large increases in the secretion of the hormone, whereas vasopressin levels remained unchanged. These findings classify oxytocin, in contrast to vasopressin, as a so-called 'stress hormone' and suggest its importance in processes other than those related to reproduction.

Animals↗

The tissue renin-angiotensin systems: focus on brain angiotensin, adrenal gland and arterial wall.

The enzyme renin has long been considered an exclusively renal enzyme responsible for the generation of angiotensin in the plasma, and angiotensin was considered a peptide hormone with specific target organs. Since renin has been discovered to occur not only in the kidney but in addition in a large number of other tissues, e.g. the salivary gland, the uterus, the blood vessels, the adrenal gland and the brain, this concept had to be revised. The possibility of local generation of angiotensin in these target tissues, where it has marked biological effects casts a new light on angiotensin as a more ubiquitous tissue factor or even a neurohormone.

Adrenal Glands↗

Immunohistochemistry of the renin-angiotensin-system in the kidney.

Changes of the intrarenal localization and concentration of renin in comparison to those of angiotensin II (ANG II) are shown under various conditions of stimulation and inhibition of the renin-angiotensin-system. Evidence is presented that ANG II which is detectable by immunocytochemical methods in epitheloid cells is formed locally within the kidney either intra- or extracellularly. ANG II-like activity was found not only in the epitheloid cells of the JGA, but also further upstream in non specialized, "plain" smooth muscle cells of the renal arterial tree and in the medial muscle cells of resistance vessels in other organs and tissues. This ANG II-like activity of resistance vessels is increased in spontaneously hypertensive rats suggesting a possible role in the long-term regulation of blood pressure.

Adrenalectomy↗

Pharmacology of converting enzyme inhibitors: new aspects.

The antihypertensive mechanism of CEI cannot be solely explained by an inhibition of the plasma RAS with reduced vasoconstrictor action of circulating ANG II. Inhibition of Kininase II with an increase of endogenous bradykinin does not appear to play a major role. Within the dose range used therapeutically, captopril and other CEI inhibit the facilitatory action of ANG II on neurogenic vasoconstriction, leading to a reduced sympathetic tone. CEI may also interfere with sympathetic reflexes. Doses above the therapeutic range seem to inhibit the sympathetic nervous system through mechanisms unrelated to CE inhibition. A reduced local generation of ANG II within tissues such as vascular wall, kidney or brain appears to contribute sympathetic tone. The type of hypertension (e.g. with or without stimulated plasma RAS or sympathetic tone) and the chemical characteristics of the CEI used (e.g. lipid solubility governing penetration into tissues) may determine the relative importance of the different mechanisms and sites of action for the reduction of blood pressure.

Angiotensin-Converting Enzyme Inhibitors↗

The brain angiotensin system: subcellular localization and interferences with converting enzyme inhibitors.

Renin is stored in synaptosomes of rat brain, separately from cathepsin D and intraneuronal angiotensin II (ANG II) has been demonstrated with the electron-microscope. Although the subcellular localization of other components of the renin-angiotensin system (RAS) have still to be investigated, these data suggest possible intracellular synthesis of ANG II in the brain. Brain ANG II is biochemically identical to the plasma peptide and corresponds to (IIe) 5-ANG II. The peptide level is unchanged after bilateral nephrectomy, and angiotensin I (ANG I) accumulation is observed in nephrectomized animals following brain angiotensin converting enzyme blockade. The significantly greater accumulation of ANG I and reduction of ANG II in stroke prone spontaneously hypertensive Wistar-Kyoto rats (WKY) indicates a higher synthesis and turnover rate of ANG II in SHR. Most converting enzyme inhibitors (CEI) penetrate the brain after chronic oral treatment. Part of their blood pressure lowering action may therefore be explained by an inhibition of the brain RAS.

Angiotensin-Converting Enzyme Inhibitors↗

Evidence against co-storage of enkephalins with noradrenaline in bovine adrenal medullary granules.

Bovine adrenal chromaffin granules were purified and separated into adrenaline (A) and noradrenaline (NA) containing granule populations by a combination of differential and isopycnic gradient centrifugation. The distribution of [Leu5]enkephalin as measured by radioimmunoassay followed a pattern identical to adrenaline but not noradrenaline on centrifugation. This suggests that enkephalins are stored in the same type of granule where adrenaline is found or that enkephalins and adrenaline even coexist in one and the same granule. Enkephalins may therefore function as co-transmitters or co-hormones of adrenaline rather than noradrenaline in the adrenal medulla.

Adrenal Medulla↗

The intrarenal renin-angiotensin-system. An immunocytochemical study on the localization of renin, angiotensinogen, converting enzyme and the angiotensins in the kidney of mouse and rat.

The localization of renin, converting enzyme (CE) and angiotensin II (ANG II) in the kidneys of rats and mice was investigated with immunocytochemical methods. According to the presence and specific intrarenal localization of these components of the renin-angiotensin-system (RAS) our results suggest that in addition to the well known systemic effects of the RAS, there are interactions of its components inside the kidney. These interactions may lead to the generation of an extra portion of ANG II in the renal blood stream with its target cells determined by the localization of CE at the luminal side of well defined endothelial areas. These intrarenal-intravasal reactions may or may not reinforce the action of "systemic" ANG II, generated prerenally. In addition, the existence of true intrarenal-interstitial interactions, with the different components and actions of this intrarenal RAS restricted entirely to the kidney is suggested by our results, particularly the demonstration of ANG II within epitheloid cells and the dissociation of systemic renin and ANG II from their local concentrations in renal hypertensive rats.

Angiotensinogen↗

Angiotensin stimulates oxytocin release: imparied response in rats with genetic hypothalamic diabetes insipidus.

Intracerebroventricularly (i.c.v.) administered angiotensin II (ANG II) at a dose of 100 ng caused a large increase in plasma oxytocin levels in Long Evans (LE) rats and in rats heterozygous for hypothalamic diabetes insipidus (HZ). In rats homozygous for diabetes insipidus (DI) even 100 fold higher doses of ANG II i.c.v. exerted only marginal effects on oxytocin release. The impaired responsiveness in DI rats was fully restored by prolonged treatment with a vasopressin (AVP) analogue. These data show that the decreased sensitivity of ANG II receptors in DI rats is due to the AVP defect and its metabolic consequences and can be reversed by AVP substitution.

Angiotensin II↗

Distribution of neurophysins in rat brain: radioimmunological measurement and characterization.

Rat neurophysins were isolated from posterior pituitaries and antibodies raised in rabbits. Individual sensitive and specific radioimmunoassays for the neurophysins associated with either vasopressin or oxytocin were developed and employed for measuring the neurophysins in various regions of rat brain. Neurophysin-like immunoreactivity was detected in hypothalamus, septum, amygdala, brainstem and spinal cord. Characterization by high performance liquid chromatography suggested the identity with the neurophysins contained in the posterior pituitary. The distribution of these peptides in the brain points to a possible role in central nervous system processes.

Animals↗

Dissociation between in vivo and in vitro measurements of converting enzyme activity after chronic oral treatment with captopril in rats.

Intravenous administration of captopril (20 micrograms) produced inhibition of angiontensin I pressor responses by 70 percent and of plasma-converting enzyme activity by 72 percent. Oral treatment with captopril (50 mg/kg/day) for 1 week inhibited angiotensin I pressor responses more (84 percent) than plasma-converting enzyme activity (23 percent). Four month oral treatment of normotensive and spontaneously hypertensive rats with captopril (50 mg/kg/day) led to 68 and 71 percent inhibition of angiotensin I pressor responses, but produced increases in plasma-converting enzyme activity of 123 and 94 percent, respectively. In spontaneously hypertensive rats, elevated converting enzyme activity in the medulla oblongata was measured after this treatment. It is concluded that plasma-converting enzyme activity measurements can be dissociated from the in vivo inhibition of converting enzyme. Chronic oral captopril treatment results in an induction of converting enzyme biosynthesis not only in peripheral tissue but also in the brain.

Angiotensin I↗

Intracerebroventricular angiotensin II increases arterial blood pressure in rhesus monkeys by stimulation of pituitary hormones and the sympathetic nervous system.

Intracerebroventricular injections of angiotensin II in anesthetized rhesus monkeys increase systemic blood pressure and heart rate. These effects are accompanied by an increase in plasma ADH, cortisol, adrenaline and noradrenaline. Angiotensin II may participate in central mechanisms of blood pressure regulation by its stimulatory effect on the sympathetic nervous system, on ADH and on ACTH release in primates.

Angiotensin II↗

SA446, a new orally active converting enzyme inhibitor: antihypertensive action and comparison with captopril in stroke-prone spontaneously hypersensitive rats.

The converting enzyme inhibitors (CEI) SA446 and Captopril (CAP) were given orally at a dose of 50 mg/kg per day to adult stroke-prone spontaneously hypertensive rats (SHRSP) over a period of four weeks. Both CEI lowered arterial blood pressure (BP) to a similar extent. CAP was more inhibitory on the plasma renin-angiotensin system (RAS) than SA446. Both CEI lowered urinary aldosterone excretion but had little (SA446) or no (CAP) natriuretic effect. CAP reduced the pressor responses to intravenous (i.v.) angiotensin I (ANG I) more (52%) than SA446 (18%) and potentiated the depressor responses to i.v. bradykinin more (fortyfold) than SA446 (tenfold). In contrast, SA446 treatment reduced the pressor responses to intracerebroventricular (i.c.v.) ANG I by 21% and led to a rise in the hypothalamic renin concentration. Oral CAP treatment for four weeks did not produce these signs of a brain converting enzyme inhibition. It is concluded that SA446 is equally as antihypertensive as CAP in SHRSP. SA446 appears to penetrate more readily into the brain and to exert its action partly through inhibition of the brain RAS which is known to be stimulated in SHRSP.

3-Mercaptopropionic Acid↗

The localization of converting enzyme in kidney vessels of the rat.

An antibody against pure rabbit lung converting enzyme (CE) showing cross-reaction with CE from other species was used for immunocytochemical studies in the kidney of rats. Using the indirect labelling PAP-technique, specific immunostaining was found in the endothelial layer of all arteries and arterioles of kidney cortex and in some descending vasa recta. CE-positive reactions were also seen in most glomeruli, the reaction product being confined to only a few capillary loops in connection with the glomerular stalk. A few immunostained capillaries in the cortical labyrinth were suspected to belong to the first ramifications of the efferent arteriole. The bulk of all other of the glomerular and peritubula capillaries as well as all veins of the kidney showed no obvious immunostaining. The functional significance of this specific localization pattern of CE in the endothelium of kidney vessels is discussed with respect to the actions of the systemic and the local, intrarenal renin-angiotensin-system on kidney functions.

Animals↗

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↗

Differential distribution of immunoreactive angiotensin and angiotensin-converting enzyme in rat brain.

To help resolve the controversy about the brain renin-angiotensin system, the distribution of immunoreactive angiotensin in the brains of male rats was analyzed using twelve different antibodies to angiotensin II, two of which had previously been reported to stain nerve fibers in the central nervous system. The distribution of angiotensin-converting enzyme immunoreactivity was also examined using an antibody to rabbit lung converting enzyme, and the distribution of this immunoreactivity was compared to that of immunoreactive angiotensin. Weak angiotensin-like immunoreactivity was found in cell bodies of the hypothalamic magnocellular nuclei of colchicine-treated rats and in nerve terminals of the median eminence, neurohypophysis, central nucleus of the amygdala, bed nucleus of the stria terminalis and various other sites in the brain and spinal cord of untreated rats. Staining could be demonstrated with only three antisera. Antigenic specificity was carefully studied in these antisera. Each was similar in that staining could be blocked with angiotensins I, II or III and tetradecapeptide renin substrate, although angiotensins II and III were most potent. Because of the relatively few angiotensin II antisera which could stain brain and because they are blockable with angiotensin I and tetradecapeptide renin substrate, the precise nature of immunoreactive angiotensin remains an open question. Intense converting enzyme-like activity was localized in endothelial cells of capillaries throughout the brain, in the subfornical organ and in the 'brush border' of choroidal epithelial cells in contact with cerebrospinal fluid. No activity was detected in neural tissue other than the subfornical organ and occasional weak activity in some ependymal elements elsewhere. These findings indicate that angiotensin and converting enzyme immunoreactivities are not co-distributed and raises several questions regarding the nature of, and pathway for, formation of immunoreactive angiotensin in the brain.

Angiotensin II↗