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Biomedical subjects

U Ganten

Publications and source records attributed to U Ganten.

At least 37 records · Page 2Linked to original sources
PubMed1991

Regulation of calcitonin gene-related peptide mRNA expression in the hearts of spontaneously hypertensive rats by testosterone.

Previous studies have demonstrated the existence of calcitonin gene-related peptide (CGRP)-immunoreactive nerve fibres and nerve cell bodies in the rat heart. Using polymerase chain reaction we have investigated whether CGRP messenger RNA (mRNA) could be detected in heart tissue of spontaneously hypertensive rats, and whether CGRP-mRNA levels are affected by gonadectomy and testosterone substitution. Two weeks after castration CGRP-mRNA levels decreased to 65.2 +/- 6.4% of control values, whereas daily dihydrotestosterone substitution reversed this effect (88.0 +/- 1.2% of control). Our results indicate that steroid hormones control the expression of intracardiac CGRP on a pretranslational level.

Animals↗
PubMed1991

Sexual dimorphism of blood pressure: possible role of the renin-angiotensin system.

The prevalence of hypertension in men is higher than in women and the onset of this disease is earlier in male than in female subjects. In spontaneously hypertensive rats, males also have higher blood pressures than females. Evidence from epidemiological, physiological, molecular biological and morphological studies concerning this sexual dimorphism is reviewed. We demonstrate that the gonadal steroids testosterone and estrogen have important effects on the gene regulation of the renin-angiotensin system. This may in part contribute to the sexual dimorphism in blood pressure control. The direct effect of steroid hormones on genes related to hypertension provides a suitable paradigm to improve our understanding of molecular and cellular mechanisms of cardiovascular control.

Angiotensin II↗
PubMed1991

The influence of cold stress on the myosin heavy chain expression of cardiac and smooth muscle in normotensive and spontaneously hypertensive female rats.

Cold exposure (6 weeks at 4 degrees C) of normotensive (Wistar-Kyoto) and stroke-prone spontaneously hypertensive female rats led to cardiac hypertrophy (in stroke-prone spontaneously hypertensive rats), increased the level of plasma thyroxine, and increased the alpha-myosin heavy chain expression in the left ventricle. In contrast, myosin heavy chain expression of both main mesenteric artery and uterus was not affected by cold stress and chronic hypertension, suggesting different regulation of myosin heavy chain expression in smooth and cardiac muscle in vivo.

Animals↗
PubMed1990

Regulation of myosin heavy chain expression in the hearts of hypertensive rats by testosterone.

Stroke-prone spontaneously hypertensive rats were used for our investigation of the influence of prepubertal gonadectomy and testosterone substitution on blood pressure, cardiac hypertrophy, and the expression of ventricular myosin heavy chain (MHC) isoenzymes at different developmental stages. Blood pressure and the degree of cardiac hypertrophy were decreased by castration and increased by testosterone substitution. We found the same relative distributions of MHC isoforms on the protein level (investigated by pyrophosphate electrophoresis) and on the messenger RNA level (investigated by the polymerase chain reaction). Castration favored the expression of the beta-MHC form, and testosterone substitution enhanced the expression of the alpha-MHC form. These effects were more pronounced in 8-week-old than in 14-16-week-old animals. We conclude that testosterone regulates cardiac MHC expression on a pretranslational level. This regulation is independent of hemodynamic load or cardiac hypertrophy.

Animals↗
PubMed1989

Glucocorticoid receptors and dissociation constant (Kd) are decreased in mononuclear leukocytes of spontaneously hypertensive rats (SHR-SP) as compared to normotensive Wistar-Kyoto rats (WKY).

We were able to show that spontaneously hypertensive stroke-prone rats (SHR-SP) have a lower number of glucocorticoid receptors (P-value is of borderline significance, 0.01 greater than P less than 0.05) with a highly significant lower Kd (P less than 0.0005), i.e higher affinity in their mononuclear leukocytes, compared to normotensive Wistar-Kyoto rats (WKY). The plasma levels of corticosterone, aldosterone and 18-hydroxycorticosterone of the two strains do not differ.

18-Hydroxycorticosterone↗
PubMed1989

Influence of parathyroidectomy on blood pressure and vascular reactivity in spontaneously hypertensive rats.

We investigated the influence of parathyroidectomy (PTX) on blood pressure (BP) and hindlimb vascular reactivity to noradrenaline (NA) and vasopressin (AVP) in male spontaneously hypertensive (SHR) and normotensive Wistar Kyoto rats (WKR). Three groups of SHR and WKR, respectively, were investigated: Sham-operated (SO) rats on a normal calcium intake (0.95%), SO rats on moderately elevated calcium intake (1.6% calcium diet) and PTX rats on the 1.6% calcium diet. At the end of the experiment (3 months), directly or indirectly measured BP was significantly lower in the PTX-SHR group on the 1.6% calcium diet than in SO-SHR on the same diet. In WKR groups, no changes of BP were recorded. Hindlimb perfusion with oxygenated Tyrode's solution for cumulative dose response curves with NA (0.1-1000 x 10(-6) M) and AVP (0.5-500 x 10(-9) M) showed no differences between PTX and SO groups. Maximal pressures and ED50 for agents used were significantly higher in SHR than WKR groups (p less than 0.05). The results support the hypothesis that the parathyroid glands contribute to high blood pressure in SHR. However, the antihypertensive action of PTX was not mediated by a change in hindlimb vascular reactivity.

Animals↗
PubMed1989

Sexual dimorphism of blood pressure in spontaneously hypertensive rats: effects of anti-androgen treatment.

The mechanisms resulting in the greater predisposition of male subjects towards hypertension were investigated in different strains of rats with genetic hypertension [spontaneously hypertensive rats of the stroke-prone strain (SHRSP) and spontaneously hypertensive rats (SHR)] and their respective normotensive controls. Blood pressure was reduced in young (9 weeks of age) hypertensive rats by (1) surgical castration, (2) treatment with the testosterone receptor antagonist cyproterone acetate (CPA), which does not elevate testosterone, or (3) with the testosterone receptor antagonist flutamide, which leads to a feedback elevation of gonadotrophic hormones and plasma testosterone. These treatments had no effect on high blood pressure in old hypertensive rats aged 25 weeks. Both androgen receptor antagonists attenuated high blood pressure development when given for the first 10 days after birth. These data clearly relate the sexual dimorphism of hypertension to testosterone produced during male brain maturation in the early phase of hypertension development. Testosterone appears not to contribute directly to the maintenance of high blood pressure in established hypertension.

Androgen Antagonists↗
PubMed1988

Chronic hypertension changes myosin isoenzyme pattern and decreases myosin phosphorylation in the rat heart.

We investigated systolic blood pressure (BP), ventricular myosin isoenzyme (MI) pattern, and myosin P-light chain phosphorylation (MP) of male and female normotensive (WKY) and spontaneously hypertensive rats (SHRSP). BP increased in SHRSP of both sexes during maturation. Male SHRSP reached a significantly higher BP (262 mmHg at week 64) than female SHRSP (217 mmHg at week 64). WKY remained at approximately 114 mmHg throughout the life-span investigated (5 to 64 weeks). MI pattern (expressed as %V1/%V3) shifted age-dependent to the V3 form: In female SHRSP MI pattern was 41/25 at week 18, 34/35 and 40/38 within week 22 to 32, and shifted to 18/53 until week 64. In male SHRSP MI pattern was 25/44 at week 18 and shifted gradually to 13/60 until week 53. MI patterns of WKY of both sexes were 100% V1 within week 5 to 12, shifted gradually to 51/23 and then remained constant until week 64. MP of the ventricle of female WKY and SHRSP was approximately 41% until week 52. At week 64, however, MP of female SHRSP decreased to 18% whereas female WKY remained at approximately 41%. MP of the ventricle of male WKY and SHRSP was approximately 38% until week 38. At week 44, however, MP of male SHRSP decreased to 22% whereas male WKY remained constant. Isometric tension generation of chemically skinned rat ventricular fibres increased after MP by calcium-calmodulin-dependent myosin light chain kinase. Both the shift to the V3 form and the decreased MP level might contribute to the development of cardiac failure in old SHRSP of both sexes.

Animals↗
PubMed1988

Effect of sodium chloride and sodium bicarbonate on blood pressure in stroke-prone spontaneously hypertensive rats.

1. To test the hypothesis that NaCl increases blood pressure, while NaHCO3 does not, we measured the effect of an NaHCO3-containing mineral water on blood pressure in stroke-prone spontaneously hypertensive (SHR-SP) and Wistar-Kyoto (WKY) rats. We compared mineral water with equimolar amounts of NaCl and demineralized drinking water in six groups of 20 rats each over 24 weeks. 2. NaCl consistently increased blood pressure in both SHR-SP and WKY compared with demineralized water, while mineral water did not. 3. We studied the possible role of sodium-regulating hormones. Sodium, potassium-dependent adenosine triphosphatase activity was decreased by NaCl and by age, but not by mineral water. The concentration of atrial natriuretic peptide was greater in SHR-SP, but was not influenced by the two regimens. Components of the renin-angiotensin-aldosterone system and 18-hydroxydeoxycorticosterone tended to decrease with NaCl, but not with mineral water. 4. Plasma pH values in the six groups of rats were not different; however, SHR-SP had consistently lower PCO2 and HCO3- values and higher anion gap values than WKY rats. These values were not influence by the two regimens. 5. NaCl elevates blood pressure in SHR-SP while NaHCO3 does not. The changes in hormones regulating sodium homoeostasis suggest that NaCl induces volume expansion while NaHCO3 does not. The effect may be related to influences on renal sodium reabsorption by chloride and bicarbonate. The possible role of increased proton excretory activity in SHR-SP remains to be determined.

Animals↗
PubMed1988

Gonadectomy and hormonal replacement changes systolic blood pressure and ventricular myosin isoenzyme pattern of spontaneously hypertensive rats.

We investigated the influence of testosterone on systolic blood pressure, heart weight, body weight, and ventricular myosin isoenzyme pattern of male spontaneously hypertensive stroke-prone rats (SHRSP). In two different study series (study 1, postpubertal; study 2, prepubertal), SHRSP were gonadectomized (HG), gonadectomized and replaced with dihydrotestosterone (HG-T), and sham-operated (H). Blood pressure was significantly higher in HG-T animals in both study series. Only prepubertal gonadectomy (study 2, HG group) led to a significantly decreased blood pressure. Heart weight and body weight were significantly diminished in the HG group when compared to the H group in study 2. Dihydrotestosterone (HG-T group) reversed this effect. In both study series gonadectomy shifted the myosin isoenzyme pattern to the V3 form while testosterone replacement led to a myosin isoenzyme pattern in favor of the V1 form. We conclude that the ventricular myosin isoenzyme pattern is under the dominant control of androgens and dissociates the expression of myosin isoenzyme from both blood pressure and cardiac hypertrophy in spontaneously hypertensive rats.

Animals↗
PubMed1988

Effect of high calcium diet on magnesium, catecholamines, and blood pressure of stroke-prone spontaneously hypertensive rats.

To test the effect of a high dietary calcium intake on blood pressure, we fed stroke-prone spontaneously hypertensive (SHR-SP) and Wistar-Kyoto rats (WKY) diets containing (a) 0.25% Ca/0.08% Mg, (b) 4.0% Ca/0.02% Mg, and (c) 4.0% Ca/0.08% mg, beginning at 6 weeks of age. SHR-SP and WKY rats receiving 4% Ca with the lower Mg content had lower blood pressures, hypomagnesemia, and hypomagnesuria, and grew poorly. SHR-SP receiving 4% Ca and the higher Mg diet had blood pressures no different from those of rats receiving the 0.25% Ca diet, in spite of having lower body weights. Rubidium flux studies in erythrocytes were not influenced by Ca or Mg in the diets. Plasma phosphate values were moderately reduced in rats receiving 4% Ca diets. Epinephrine and norepinephrine values were higher in SHR-SP than in WKY rats. Norepinephrine increased with stress in both strains, independent of diet. Epinephrine values were lower in SHR-SP receiving the 4% Ca diets and showed less of an increase with stress compared to SHR-SP receiving the 0.25% Ca diet. After 26 weeks of diets, SHR-SP and WKY rats were given 0.9% NaCl in their drinking water. NaCl increased blood pressure in SHR-SP irrespective of Ca content of the diet. These data suggest that a high Ca diet influences Mg homeostasis and adrenal medullary function in SHR-SP. Further, SHR-SP appear resistant to any blood pressure lowering effect of Ca irrespective of NaCl intake.

Animals↗
PubMed1987

Blood pressure, electrolyte and adrenal responses in swim-trained hypertensive rats.

In order to test the effect of aerobic training on blood pressure, and to examine the putative mechanisms involved, stroke-prone spontaneously hypertensive rats (SHR-SP), borderline hypertensive rats (BHR), and Wistar-Kyoto control rats (WKY) were swim-trained for up to 1.5 h twice-daily for 22 weeks. The BHR were F1 back-cross SHR-SP, WKY. A training effect was observed in the trained rats compared to controls, as demonstrated by slower heart rates, heavier hearts and increased cytochrome oxidase activity in their skeletal muscle. Trained SHR-SP and BHR had significantly lower blood pressures at the end of the intervention period (approximately 10 mmHg) compared to controls. Acute increases in blood pressure with swimming were less in trained than in untrained rats. Trained rats had higher extracellular sodium values than untrained rats. Further, trained SHR-SP and BHR had lower intra-erythrocyte sodium values than controls. Increases in corticosterone, epinephrine and norepinephrine with swimming were less in trained rats than in controls. We conclude that exercise conditioning ameliorates hypertension in rats. The mechanism may involve an effect on cation transmembrane transport, as well as decreased, adrenosympathetic tone. Moreover, these effects may be related.

Adaptation, Physiological↗
PubMed1987

Haemodynamic effects of intact digoxin antibody and its Fab fragments in experimental hypertension.

The effects of i.v. injection of intact digoxin antibody (0.3 mg/rat) and of its Fab fragment (40 mg/rat) on blood pressure, cardiac output and total peripheral resistance were measured in conscious spontaneously hypertensive and deoxycorticosterone hypertensive rats. In vitro findings showed that Fab fragment bound radio-labelled digoxin, digitoxin and ouabain more efficiently than did intact antibody. In vivo, Fab fragment prevented the increase of total peripheral resistance induced by i.v. injection digoxin. However, Fab fragment of digoxin antibody did not alter blood pressure, cardiac output or total peripheral resistance in normal and salt-loaded spontaneously hypertensive rats (SHR) in uraemic SHR and in deoxycorticosterone hypertensive rats. We confirmed that intact digoxin antibody--bearing Fc domains with complement activating properties--lowered blood pressure in SHR and in deoxycorticosterone hypertension. This was due to a decrease in total peripheral resistance. Our data suggest that a circulating endogenous digitalis-like factor is unlikely to be important in blood pressure regulation in salt-loaded hypertension in the rat.

Animals↗
PubMed1987

Effects of parathyroidectomy on blood pressure in spontaneously hypertensive rats.

The long-term effects of parathyroidectomy (PTX) on blood pressure, intravascular volume, pressor hormones, and on acute vascular effects of intravenous parathyroid hormone (PTH) were evaluated in spontaneously hypertensive (SH) and normotensive Wistar-Kyoto (WK) rats. PTX or sham operation (CO) were done at 4-5 weeks of age, and a high calcium diet was offered to PTX rats to study them at eucalcemic calcium levels. The cardiovascular effects of PTX, determined after 11-13 weeks, were qualitatively similar in SH and WK rats: mean arterial blood pressure (conscious unrestrained rats) was lower, intravascular volume was higher, total body sodium was slightly higher, and plasma angiotensin II or norepinephrine levels were not different from CO groups. The acute hypotensive and chronotrophic effect of intravenous PTH was unchanged in PTX groups. When parathyroid intact SH rats and PTX SH rats were both examined on an 1.6% Ca diet, blood pressure was significantly lower in PTX than in parathyroid-intact SH rats. The results are compatible with the hypothesis that PTH has a permissive action on blood pressure maintenance in eucalcemic SH and WK rats by mechanisms unrelated to volume status or circulating pressor hormone concentrations.

Animals↗
PubMed1986

Myosin isoenzymes of vascular smooth and cardiac muscle in the spontaneously hypertensive and normotensive male and female rat: a comparative study.

Cardiac hypertrophy in hypertensive subjects, its biochemical markers, and functional consequences are of great clinical importance but still unclear. We observed a shift of the ventricular isomyosin of adult spontaneously hypertensive (H) rats of both sexes to the V3 form and a decreased myofibrillar ATPase activity in the H animals when compared to normotensive (N) controls. Compared to the male H rats, age-matched female H animals revealed a lower blood pressure, the same or even an elevated magnitude of cardiac hypertrophy, a different ventricular isomyosin pattern, and a higher myofibrillar ATPase activity. In female H rats the V1 and V3 isomyosins were equally distributed (35% V1 and 35% V3), but in male H animals the V3 was predominant (24% V1 and 45% V3). The Ca2+-regulated Mg2+-dependent myofibrillar ATPase of the rat ventricle correlated positively with the amount of V1 when measured at pCa 5 (maximum activation). At submaximum Ca2+-concentrations (pCa 6.9-5.9) the myofibrillar ATPase activities were not changed with the proportion of V1. The cooperativity of the Ca2+-activation of the myofibrillar ATPase increased with increasing amount of V1 (Hill-coefficient 3.7 with 100% V1) and decreased with increased proportion of V3 (Hill-coefficient 1.3 at 45% V3). Two myosin isoenzymes were detected in the aorta of rats, a slow migrating (S2) and a fast migrating (S1) form having both a higher mobility than the ventricular isomyosins. Only one band was observed in the portal vein, which revealed the same mobility as S2. Hypertension did not change the appearance of these vascular smooth muscle isomyosins neither in male nor in female animals.

Animals↗
PubMed1985

Antibiotics attenuate experimental hypertension in rats.

Hypertension was produced in Sprague-Dawley rats by intramuscular injections of either corticosterone or ACTH. Lower increases in blood pressure to these challenges were observed in Sprague-Dawley rats pretreated with neomycin or vancomycin which alone had no effect on blood pressure or growth. The development of high blood pressure in spontaneously hypertensive rats of a stroke-prone substrain was also attenuated by oral administration of neomycin. These results suggest that experimental hypertension can be modulated by the administration of antibiotics.

Adrenocorticotropic Hormone↗
PubMed1984

Pathogenesis of hypertension in spontaneously hypertensive rats: definite evidence against a pressor role of vasopressin.

A number of experiments were performed in order to investigate the possible importance of vasopressin (AVP) in the pathogenesis of high blood pressure in spontaneously hypertensive rats of the stroke prone strain (SHRSP). Radioimmunological studies revealed reduced concentrations of AVP in the plasma and brain of SHRSP as compared to normotensive controls. Intravenous administration of an AVP pressor antagonist had no significant influence on mean arterial blood pressure, cardiac output and total peripheral resistance in SHRSP. Crossbreeding of SHRSP with rats homozygous for hypothalamic diabetes insipidus resulted in the development of a new strain of rats which show high blood pressure despite of a complete lack in AVP. These results argue strongly against a pressor role of AVP in the development or maintenance of hypertension in SHRSP.

Animals↗