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Biomedical subjects

H Geiger

Publications and source records attributed to H Geiger.

At least 91 records · Page 5Linked to original sources

Atrial natriuretic peptide in the locus coeruleus and its possible role in the regulation of arterial blood pressure, fluid and electrolyte homeostasis.

Atrial natriuretic factor (ANP) is present in neuronal cells of the locus coeruleus and its vicinity in the pontine tegmentum and moderate amount of ANP is detectable in this area by radioimmunoassay. The ANP (both peripheral and brain-born) is known as a neuropeptide which may influence the body salt and water homeostasis and blood pressure by targeting both central and peripheral regulatory mechanisms. Whether this pontine ANP cell group is involved in any of these regulatory mechanisms, the effect of various types of hypertension and experimental alterations in the salt and water balance on ANP levels was measured by radioimmunoassay in the locus coeruleus of rats. Adrenalectomy, as well as aldosterone and dexamethasone treatments failed to alter ANP levels in the locus coeruleus. Reduced ANP levels were measured in spontaneously hypertensive (both young and adult) rats, and in diabetes insipidus (Brattleboro) rats with vasopressin replacement. In contrast to these situations, elevated ANP levels were found in rats with DOCA-salt or 1-kidney-1-clip hypertension. These data suggest a link between ANP levels in the locus coeruleus and fluid volume homeostasis. Whether this link is causal and connected with the major activity of locus coeruleus neurons (noradrenergic influence on brain regulatory activities) needs further informations.

Adrenalectomy↗

Changes in the central ANF-system of renovascular hypertensive rats.

The central atrial natriuretic peptides (ANF)-system was investigated in volume-dependent, one-kidney, one-clip (1K1C) and renin-dependent two-kidney, one-clip (2K1C) renovascular hypertensive rats by radioimmunological measurement of ANF concentration in 18 selected brain areas. Significant changes were found in nine brain areas of 1K1C and in eight brain areas of 2K1C hypertensive rats. Except undirectional changes in the organum vasculosum laminae terminalis and the supraoptic nucleus, ANF concentration was changed in the opposite direction in all other brain areas, with an activation of the central ANF system in 1K1C and an inhibition in 2K1C hypertension. The localization of the alterations (circumventricular organs, anteroventral third ventricle region, hypothalamo hypophyseal system, brain stem) implies major differences in the central regulation of blood pressure and electrolyte and fluid homeostasis between these two models. The activation of the central ANF system in 1K1C hypertension may be a compensatory mechanism to prevent further increments in blood pressure and plasma volume. In contrast, the depression of the central ANF system in 2K1C hypertension may promote the elevation of the blood pressure.

Animals↗

Effects of aldosterone and dexamethasone on atrial natriuretic peptide levels in preoptic and hypothalamic nuclei of adrenalectomized and intact rats.

The effect of aldosterone and dexamethasone on the concentrations of atrial natriuretic peptide (ANP) in preoptic and hypothalamic nuclei was examined in adrenalectomized and intact rats. Five days after adrenalectomy, increased ANP levels in those brain areas which control water intake, i.e. in the subfornical organ, supraoptic nucleus, and in the so-called hypothalamic drinking centers (perifornical nucleus, lateral hypothalamic area) were measured. In contrast to this, adrenalectomy decreased ANP levels markedly in the organum vasculosum laminae terminalis and preoptic periventricular nucleus, which are reportedly involved in the central regulation of salt and water homeostasis. ANP contents of these two preoptic structures were restored almost completely by daily administration of 0.9% sodium chloride or aldosterone but not dexamethasone. The daily administration of aldosterone elevated ANP levels in the supraoptic, paraventricular and perifornical nuclei as well as in the lateral hypothalamus both in control and adrenalectomized rats. Dexamethasone which was without any significant effect on preoptic and hypothalamic nuclei in control rats elevated ANP levels in the supraoptic and perifornical nuclei and in the lateral hypothalamic area of adrenalectomized animals. Since neither adrenalectomy, nor aldosterone or dexamethasone treatment influenced plasma ANP levels, altered ANP contents measured in preoptic and hypothalamic nuclei may represent a direct effect of adrenal corticoids (mainly aldosterone) on brain ANP-containing neurons which may participate in the control of body fluid and electrolyte homeostasis.

Adrenalectomy↗

[Regulation of thirst in end-stage kidney insufficiency].

About 30% of hemodialyzed patients are suffering from chronic fluid overload despite advice to restrict the oral fluid intake. To investigate the cause of the abnormal drinking behaviour a clinical study was performed in 51 non-diabetic patients with endstage renal disease exhibiting lower interdialysis weight gain (less than 3 kg, n = 17) and increased interdialysis weight gain (greater than 3 kg, n = 34). Blood pressure, body weight self-estimated thirst intensity before and after hemodialysis were analyzed. Biochemical and behavioral variables were measured including hormonal factors of water and sodium metabolism. Significant differences of dry weight, creatinine, urea nitrogen and thirst intensity were found between the two groups. Catecholamines, renin, angiotensin II, aldosterone, vasopressin and atrial natriuretic peptide exhibited a similar pattern in both groups. Atrial natriuretic peptide decreased during hemodialysis in both groups, angiotensin II, however, and norepinephrine showed an exaggerated response to ultrafiltration rate in polydipsic patients. These results suggest that changes in serum osmolality during hemodialysis did not contribute to thirst and drinking behaviour. It seems that postdialytic hypovolaemia together with higher plasma-angiotensin II-levels is responsible for increased oral intake of fluid and excessive weight gain.

Angiotensin II↗

Atrial natriuretic peptides in brain nuclei of rats with inherited diabetes insipidus (Brattleboro rats).

The concentration of atrial natriuretic peptides (ANF) was measured radioimmunologically in 18 selected microdissected brain areas of rats with inherited diabetes insipidus (Brattleboro rats) and their control rats (Long-Evans rats). In 7 brain areas known to be involved in the regulation of fluid homeostasis or blood pressure (subfornical organ, organum vasculosum lamina terminalis, periventricular preoptic nucleus, perifornical nucleus, nucleus of the solitary tract, tegmentum pontis, arcuate nucleus) ANF concentration was significantly changed. After restoration of antidiuresis with the V2 receptor agonist 1-desamino-8-D-arginine vasopressin (DDAVP) ANF levels of Brattleboro rats adapted at least partly to those of the control rats in all brain areas except the subfornical organ. Furthermore, ANF was then significantly changed in the supraoptic and paraventricular nuclei of DDAVP-treated diabetes insipidus rats. These data show that the central ANF system is sensitive for changes in electrolyte and fluid homeostasis.

Animals↗

Impaired response to intrarenal administered atrial natriuretic peptide in ischemic acute renal failure of a transplanted patient.

A 30-year-old male patient suffering from membrano-proliferative glomerulonephritis was transplanted a cadaveric kidney 3 years ago. Five days later the transplant was removed because of fresh thrombosis in larger arteries. Three years after first transplantation a second graft was transplanted. Repeated perfusion scintigraphies of persistent anuric patient showed a delayed perfusion of renal parenchyma, no intrarenal bolus was obtained. Urgently, an arterial angiography was performed. It demonstrated that calibers of renal parenchymal vasculature were narrowed. Suggesting ischemic nature of acute renal failure, 50 micrograms human atrial natriuretic peptide (hANP) was injected intrarenally as bolus. Five minutes after hANP injection in a second angiography a significant improvement of renal blood flow was demonstrated but no amelioration of urine production or electrolyte excretion was observed. Histologically an ischemic lesion of transplant was proven. This finding indicates a blunted excretory response of acute renal failure after kidney transplantation despite of significantly ameliorated renal blood flow visualized radiologically.

Acute Kidney Injury↗

Effect of atrial natriuretic peptide on the adenylate cyclase activity in the anterior and neurointermediate pituitary lobes of rats.

The effect of two atrial natriuretic peptides, rat ANP (3-28) and synthetic ANP (Arg101-Tyr126), on pituitary adenylate cyclase activity was measured in rats. Neither one was effective on basal, forskolin- or guanylylimidodiphosphate (GMP-PNP)-stimulated adenylate cyclase levels measured in homogenates of anterior and neurointermediate pituitary lobes. High concentrations (10(-7) and 10(-6) M) of ANPs further stimulate NaF-induced high adenylate cyclase activity - ANP (3-28) in both lobes, ANP (Arg101-Tyr126) only in the anterior lobe-but they were without effect in 10(-8) M or lower concentrations. These data indicate that ANP may not influence adenylate cyclase/cAMP system in the rat pituitary gland.

Adenylyl Cyclases↗

Atrial natriuretic factor in central nervous system regulatory mechanisms: effect of experimental alterations in water and salt homeostasis and blood pressure.

Concentrations of atrial natriuretic factor (ANF) were measured in discrete brain nuclei by radioimmunoassay in rats. Alterations in the salt and fluid homeostasis and aldosterone treatment resulted in marked changes of ANF levels in the preoptic-hypothalamic periventricular structures including the organum vasculosum laminae terminalis, in the subfornical organ and the perifornical nucleus. Furthermore, marked changes were observed in ANF levels of these nuclei in various types of renal hypertensions. Altered ANF levels were found in several brain nuclei (locus coeruleus, dorsal raphe nucleus, tegmentum pontis, nucleus of the solitary tract) of animals with diabetes insipidus or spontaneous hypertension.

Animals↗

Atrial natriuretic factor in central nervous system regulatory mechanisms: effect of experimental alterations in water and salt homeostasis and blood pressure.

Atrial natriuretic factor (ANF) is widely distributed in the preoptic area and the hypothalamus, it is present there both in cell bodies and nerve terminals. Effect of experimental alterations in the salt and water balance was examined on preoptic-hypothalamic ANF levels measured in ten microdissected nuclei. Immunohistochemical analysis was also performed to confirm radioimmunological results. Following interventions were performed in adult male rats: adrenalectomy (5 days), daily 0.9% NaCl, aldosterone (5 micrograms/100 g) and dexamethasone (2 micrograms/ml drinking water) treatments in both intact and adrenalectomized groups, and in rats with diabetes insipidus (Brattleboro rats) and DOC-salt hypertension. Although no appreciable alterations were observed in the intensity of ANF-like immunoreactivity in sections of the preoptic-hypothalamic region, ANF levels altered markedly in the periventricular structures (organum vasculosum laminae terminalis, preoptic and periventricular nuclei). Little or no changes were measured in ANF levels of other hypothalamic nuclei (except the perifornical nucleus). Adrenalectomy depleted ANF levels which were restored by NaCl drinking. Aldosterone elevated ANF concentrations both in intact and adrenalectomized animals while dexamethasone treatment was without any significant effect on ANF levels in the periventricular preoptic nucleus. Diabetes insipidus or DOC-salt hypertension had little or no effect on ANF levels in this brain area. Unchanged ANF concentrations were also measured in the vasopressin-containing supraoptic nucleus following adrenalectomy or in diabetes insipidus rats.

Animals↗

Atrial natriuretic factor content of brain nuclei in deoxycorticosterone acetate-salt hypertension in the rat.

1. The influence of deoxycorticosterone acetate (DOCA)-salt hypertension on brain atrial natriuretic factor (ANF) in rats was investigated to elucidate the role of central ANF in a renin-independent model of experimental hypertension. 2. Sprague-Dawley rats were subjected to uninephrectomy and given either tap water or saline [1% (w/v) NaCl] to drink plus weekly injections of either saline or DOCA (25 mg/kg, subcutaneously). After 32 days, the rats were decapitated and 18 different brain nuclei were removed by a micropunch technique. 3. The systolic blood pressure of the DOCA-salt rats was significantly higher than that of control rats [154 +/- 3 mmHg vs 104 +/- 2 mmHg (20.53 +/- 0.40 kPa vs 13.86 +/- 0.27 kPa), P less than 0.001]. 4. Plasma ANF levels were significantly (P less than 0.01) higher in DOCA-salt hypertensive rats compared with control rats. 5. In DOCA-salt hypertensive rats, the ANF content was increased in the organum vasculosum of the lamina terminalis (31.4 +/- 2.1 vs 22.1 +/- 2.5 pg/mg of protein, P less than 0.05), the subfornical organ (32.5 +/- 5.0 vs 24.2 +/- 2.4 pg/mg of protein, P less than 0.05), the medial amygdaloid nucleus (49.0 +/- 6.4 vs 34.0 +/- 2.0 pg/mg of protein, P less than 0.05) and the locus coeruleus (86.9 +/- 4.1 vs 64.4 +/- 4.2 pg/mg of protein, P less than 0.01) compared with control rats. The ANF content of 14 other brain areas investigated did not alter after treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Amygdala↗

Atrial natriuretic peptide in brain preoptic areas: implications for fluid and salt homeostasis.

The influence of adrenalectomy and mineralocorticoid and glucocorticoid treatment on atrial natriuretic peptide (ANP) concentration of 18 microdissected rat brain nuclei was investigated. Adrenalectomy increased ANP levels highly in those brain areas that control water intake (the subfornical organ and supraoptic nucleus) and in the drinking center (the perifornical nucleus and the lateral hypothalamus). In all of these brain regions, aldosterone elevated ANP levels in intact animals. Adrenalectomy decreased ANP levels markedly in the OVLT and preoptic periventricular nucleus, which constitute the so-called AV3V region. The ANP level of these two brain areas was nearly restored to baseline levels both after administration of sodium chloride and after replacement of aldosterone, whereas dexamethasone treatment failed to have any effect.

Adrenalectomy↗

Does cadmium contribute to the development of renal parenchymal hypertension?

In our study we investigated 36 out-patients with renal disease, 22 of whom were hypertensive. In all patients proteinuria was present (4.30 +/- 5.05 g protein/day) and kidney diseases were verified by renal biopsy. Blood cadmium in non-smokers was significantly (p less than 0.05) lower than in smokers. We found a positive correlation between cadmium-concentration of blood and urine (p less than 0.01, R = 0.44) and between cadmium-concentration of blood and blood uric acid (p less than 0.01, R = 0.44). Proteinuria was weakly correlated with cadmium concentration of urine (p less than 0.05, R = 0.35). Patients with renal hypertension showed a significantly higher (p less than 0.05) urine cadmium excretion per day (1.60 +/- 1.12 micrograms/day) compared to normotensives with a disease of the kidney (1.14 +/- 1.47 micrograms/day). Our results indicate that cadmium may be involved in the development of hypertension in patients with renal disease.

Cadmium↗

Cadmium and renal hypertension.

In our study we investigated 36 patients with renal disease, 22 of whom were hypertensive. In all proteinuria was present (4.30 +/- 5.05 g protein/day) and renal lesions were proved by renal biopsy. Blood cadmium in non-smokers was significantly (P less than 0.05) lower than in smokers. We found a positive correlation between cadmium concentrations in blood and urine (P less than 0.01, r = 0.44) and between cadmium concentration in blood and serum uric acid levels (P less than 0.01, r = 0.44). Proteinuria was weakly correlated with cadmium concentration in urine (P less than 0.05, r = 0.35). Patients with hypertension showed a significantly higher (P less than 0.05) urine cadmium excretion per day (1.60 +/- 1.12 micrograms/day compared with normotensives with disease of the kidney (1.14 +/- 1.47 micrograms/day). Our results indicate that cadmium may be involved in the development of hypertension in patients with renal disease.

Cadmium↗

Role of cadmium in hypertensive patients with renal parenchymal disease.

In our study we investigated 36 out-patients with renal disease; 22 of them were hypertensive. In all patients proteinuria was present (4.30 +/- 0.82 g protein/d) and renal involvement has been proved by renal biopsy. Blood cadmium in nonsmokers was significantly (P less than .05) lower than in smokers. Patients with renal hypertension showed a significantly higher (P less than .05) urine cadmium excretion/d (1.60 +/- 0.23 micrograms/d) compared to normotensives with a disease of the kidney (1.14 +/- 0.38 micrograms/d). Our results indicate that cadmium may be involved in the development of hypertension in patients with renal disease.

Cadmium↗

Improved sexual function in hemodialysis patients on recombinant erythropoietin: a possible role for prolactin.

As it was reported that correction of anemia in long-term hemodialysis patients by recombinant human erythropoietin (r-HuEPO) is associated with improved sexual function, we conducted the present study to further delineate the mechanism(s) by which this is brought about. Serum prolactin, testosterone, and parathyroid hormone (PTH) levels were followed during 4 months of r-HuEPO therapy. Within 4 months of treatment with r-HuEPO, hematocrit values rose from 23.7 +/- 1.2 to 35.7 +/- 0.2% and hemoglobin increased from 7.3 +/- 0.3 to 11.3 +/- 0.4 g/100 ml. In parallel, serum prolactin values decreased significantly from 66.9 +/- 9.3 to 9.6 +/- 2.6 ng/ml in females and from 39.5 +/- 10.5 to 10.3 +/- 1.0 ng/ml in male dialysis patients. Testosterone concentrations were low in male patients and remained unchanged during r-HuEPO therapy. Baseline PTH values were elevated (1,880 +/- 220 pg/ml) in patients of both sexes and declined to 1,410 +/- 180 pg/ml during treatment with r-HuEPO. However, this difference did not reach statistical significance. Sexual function improved in 4 out of 7 males and 5 out of 9 female patients began to menstruate regularly again. It appears that treatment of anemia in end-stage renal disease by r-HuEPO improves sexual function via normalization of elevated serum prolactin concentrations.

Adult↗

Glandular adenylate cyclase system in genetic hypertension: age-dependent response to catecholamines.

The parotid excretion of cAMP was measured in normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) in this study. In addition, adenylate cyclase activity in parotid gland tissue was determined. The cAMP excretion rate was increased immediately after isoproterenol infusion. This elevation was more pronounced in young (6-8 weeks) than in older (16-18 weeks) animals, both in WKY and in SHR. These data demonstrate a diminished cAMP response to isoproterenol application with respect to the age of the animals. This could indicate that there is an age-dependent functional alteration of the beta-adrenoceptor-adenylate cyclase complex. In agreement with the results of these in vivo studies, the stimulation of adenylate cyclase activity of the parotid gland by isoproterenol or fluoride was enhanced in young SHR and lowered in old SHR when compared to their normotensive controls of the same age. One may conclude that the sympathetic activity is enhanced in young SHR, and that the beta-adrenoceptor system is hypersensitive to adrenoceptor agonists. This might contribute to the development of hypertension in SHR. Sixteen to eighteen weeks old SHR showed a diminished cAMP output following isoproterenol application when compared to normotensive control rats of the same age. The reduction of the response to isoproterenol stimulation in old SHR seems to be related to a reduced sensitivity to catecholamine stimulation.

Adenylyl Cyclases↗