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Biomedical subjects

D Ganten

Publications and source records attributed to D Ganten.

At least 451 records · Page 25Linked to original sources
PubMed1981

Vasopressin-induced increase in total peripheral resistance in deoxycorticosterone acetate hypertensive rats is buffered by the baroreceptor reflex.

1. The role of arginine-vasopressin (AVP) in the maintenance of high blood pressure in rats with deoxycorticosterone acetate (DOCA) hypertension was investigated. 2. Plasma concentrations of AVP were significantly elevated in DOCa hypertensive rats compared with normotensive control rats, whether or not they received 1% sodium chloride solution or demineralized water to drink. 3. The specific antagonist of the vasopressor response to AVP, d(CH2)5VDAVP (100 microgram/kg intravenously), significantly increased cardiac output and decreased total peripheral resistance, but had no effect on mean arterial pressure in DOCA hypertensive rats. No changes of mean arterial pressure, cardiac output and total peripheral resistance were observed in the normotensive control groups after d(CH2)5VDAVP. 4. After sino-aortic baroreceptor deafferentation, d(CH2)5VDAVP decreased mean arterial pressure in DOCA--salt hypertensive rats, but not in the control groups. 5. It is concluded that elevated circulating AVP causes vasoconstriction in DOCA hypertensive rats. The AVP-induced increase in total peripheral resistance is counter-regulated by an activation of the baroreceptor reflex and subsequent reduction in cardiac output.

Animals↗
PubMed1981

Plasma angiotensin II concentrations and experimentally induced thirst.

The systemic administration of angiotensin II or its precursors will result in increased water intake. Several manipulations that result in hypovolemia and/or hypotension (extracellular thirst challenges) are known to activate the peripheral renin-angiotensin system and also produce drinking. Although there are without question multiple mediators of thirst associated with extracellular thirst challenges, one of the major factors responsible for water intake has been hypothesized to be the action of angiotensin II. In the experimental analysis of thirst, several types of hypovolemic-hypotensive manipulations have been employed. However, there is a paucity of data available that characterize the systematic changes of angiotensin II levels following such challenges. The present studies determined plasma angiotensin II levels and drinking responses after isoproterenol administration, caval ligation, and subcutaneous polyethylene glycol treatment. The experimental protocols for treatment of the animals closely approximated conditions commonly employed in the experimental analysis of thirst. The results indicated that endogenous levels of angiotensin II increase after these treatments to levels that in all likelihood are sufficient to make a substantial contribution to the drinking response.

Angiotensin II↗
PubMed1981

Isoproterenol-induced thirst: renal and extrarenal mechanisms.

When given systemically, isoproterenol will induce water intake in various species. The drug also causes hypotension and renin release from the kidney. Angiotensin II and arterial baroreceptors have been hypothesized to be involved in the mediation of beta-adrenoceptor agonist-induced thirst, but their relative importance has been disputed. In the present series of experiments, isoproterenol was infused intravenously at different rates into nephrectomized and ureteric-ligated rats. Thus, different levels of hypotension could be achieved and maintained while water intake was measured. Also, plasma levels of angiotensin II were determined in ureteric-ligated rats following the intravenous infusion of a dipsogenic dose of isoproterenol. The results indicate that for moderate blood pressure changes a renal-related factor, probably angiotensin II, plays a major role in the mediation of isoproterenol-induced thirst. Under extreme conditions involving a very dramatic drop of arterial blood pressure, extrarenal mechanisms (e.g., arterial baroreceptors) are implicated.

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

Studies on the juxtaglomerular apparatus. VI. Sympathetic innervation, catecholamines and the renin-angiotensin-system in rats and tree-shrews (Tupaia belangeri).

It has previously been reported that the primitive primate Tupaia belangeri develops a renal failure when exposed to psychosocial stress. In order to learn if this high susceptibility to stress of the Tupaia kidney can be correlated with morphological and functional parameters of the juxtaglomerular apparatus (JGA) and the renin-angiotension system, comparative experiments were performed on Tupaia and rat. Our results reveal an outstandingly high potency of the JGA and the renin-angiotensin system in Tupaia as evident from the following findings: The Tupaia JGA contains a great number of epithelioid cells abounding in renin granules (electron microscopy). The renin content of the Tupaia kidney is considerably higher than in the rat (radio-immunoassay). The sympathetic innervation of the kidney and especially of the JGA is abundant in Tupaia (fluorescence and electron microscopy). Catecholamine contents of the kidney and other organs are significantly higher in Tupaia than in rats (spectrophotofluorometry). Our results support the previously developed concept of a potent intrarenal neuroendocrine interaction at the JGA level favouring, under certain conditions of social stress, the development of acute renal failure in Tupaia belangeri.

Angiotensins↗
PubMed1980

Renin-like immunocytochemical activity in the rat and mouse brain.

Renin-like immunoreactivity could be demonstrated in the nuclei paraventricularis, periventricularis and supraopticus of the hypothalamus and in the cerebellar cortex of rats and mice, with both the peroxidase-antiperoxidase (PAP) and fluorescence techniques. The findings are consistent with the assumption of an endogenous angiotensin-forming system in the brain.

Animals↗
PubMed1980

Brain angiotensin II stimulates release of pituitary hormones, plasma catecholamines and increases blood pressure in dogs.

1. The mechanisms of central angiotensin II blood pressure effects in conscious dogs on normal or sodium-deficient diets were examined. 2. The biosynthesis of brain angiotensin II in cerebrospinal fluid from its local precursor angiotensinogen was induced in vivo by injection of 0.5 unit of hog kidney renin through a chronically implanted cannula into the third brain ventricle in conscious dogs. 3. Intracerebroventricular administration of renin induced an increase of arterial blood pressure and a marked drinking response under both dietary regimens. Sodium restriction had no effect on the magnitude of the central angiotensin pressor response. 4. Plasma concentrations of renin and angiotensin II decreased, and plasma antidiuretic hormone, noradrenaline, adrenaline and corticosterone increased, in both groups of dogs. 5. Simultaneous intraventricular administrations of captopril with renin inhibited the central renin effects. Intracerebroventricular injections of [Sar1, Val5, Ala8] angiotensin II alone increased plasma renin and angiotensin II concentrations. 6. It is concluded that endogenous brain angiotensin II participates in central mechanisms of blood pressure regulation by the stimulation of the release of antidiuretic hormone, adrenocorticotrophic hormone, adrenaline and noradrenaline.

Angiotensin II↗
PubMed1980

Blood pressure and heart rate responses to centrally administered substance P are increased in spontaneously hypertensive rats.

1. The cardiovascular effects after intracerebroventricular injections of substance P were investigated in normotensive Wistar-Kyoto and in spontaneously hypertensive rats. 2. Substance P increased blood pressor in both rat strains. Wistar-Kyoto rats responded with moderate, dose-dependent blood pressure increases, and heart rate decreased; spontaneously hypertensive rats showed two- to three-fold increased pressor effects and, concomitantly, marked heart rate increases to intracerebroventricular injections of substance P. 3. Sino-aortic baroreceptor denervation rendered Wistar-Kyoto rats supersensitive to intracerebroventricular substance P to a similar degree as unoperated spontaneously hypertensive rats. Sino-aortic denervation had no effect on the blood pressure responses to the peptide in spontaneously hypertensive rats. 4. The central pressure actions of substance P could be markedly attenuated by intracerebroventricular pretreatment with the derivative of gamma-aminobutyric acid, baclofen. 5. We conclude that the baroreceptor reflex is disturbed in spontaneously hypertensive rats. Substance P may contribute to the pathogenesis of hypertension. The effector pathways appear to be different from angiotensin.

Angiotensin II↗
PubMed1980

Is arterial media hypertrophy in spontaneously hypertensive rats a consequence of or a cause for hypertension?

1. The increased peripheral resistance observed in established hypertension has been attributed to structural changes in the resistance vessels, which are considered to be due mainly to medial hypertrophy. This study was undertaken to examine the possibility that structural changes in the arterial bed are genetically determined and may be causative factors in the development of high blood pressure in the spontaneously hypertensive rat. 2. The wall dimensions of aorta, renal artery and intrarenal arteries down to a distended diameter of 35 micrometer were studied: (a) in 14-week-old spontaneously hypertensive rats; (b) in age- and sex-matched spontaneously hypertensive rats which had been treated with captopril for two generations and had been normotensive during their complete life span; (c) in normotensive Wistar-Kyoto control rats. 3. Cross-sectional areas of the media were increased in the hypertensive rats in comparison with 'normotensive spontaneously hypertensive rats' and Wistar-Kyoto rats. Increased numbers of smooth muscle cells were found in the major arteries of hypertensive animals. 4. These results indicate that hypertrophy of the media is a consequence of high blood pressure rather than a genetically determined pathogenetic factor for the development of hypertension in spontaneously hypertensive rats.

Animals↗
PubMed1980

Plasma angiotensin II: dipsogenic levels and angiotensin-generating capacity of renin.

Activation of the renin-angiotensin system (RAS) or administration of angiotensin II (AII) will induce water intake. In the rat, the species in which the physiological mechanisms of thirst have been most thoroughly studied, the levels of circulating AII produced by systemic administration of dipsogenic doses of the octapeptide have not been established. Furthermore, the capacity of the endogenous RAS to generate AII sufficient to contribute to the production of a thirst state has not been well studied. In the present series of investigations, plasma levels of AII were determined following infusions of the peptide over a range of doses frequently employed in studies on thirst. In addition, a series of manipulations ranging from mild water deprivation or ingestion of a dry meal to ether stress of rats with malignant renal hypertension was applied to examine the capacity of the RAS to generate angiotensin. The results indicate that the endogenous RAS can readily produce the major effector peptide of the system so that circulating levels are well in excess of the dipsogenic threshold for AII.

Anesthesia↗
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↗