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Biomedical subjects

D Ganten

Publications and source records attributed to D Ganten.

At least 307 records · Page 17Linked to original sources
PubMed1988

Renin-dependent water intake in hypovolemia.

The role of the renin-angiotensin system as a mediator of water intake, induced by hypovolemia after polyethylene glycol (PEG) injection, was investigated. Blockade of angiotensin I converting enzyme and of angiotensin receptors was used as a pharmacological tool. A significant reduction of water intake was observed when angiotensin I converting enzyme was inhibited by captopril and enalapril. In PEG-treated rats with blockade of angiotensin I converting enzyme, hypertonic saline injection continued to elicit substantial drinking. Normalization of low blood pressure by vasopressin infusions in PEG and captopril treated rats did not interfere with the antidipsogenic effectiveness of converting enzyme blockade. The angiotensin II receptor antagonist, saralasin, also reduced PEG-induced drinking although less effectively than converting enzyme inhibitors. We conclude that water intake due to isotonic depletion of the extracellular fluid compartment may depend on the activity of the renin-angiotensin system.

Angiotensin II↗
PubMed1988

In situ hybridization demonstrates vasopressin gene transcription in hypothalamic neurons of crossbred hypertensive x diabetes insipidus rats.

In situ hybridization, Northern blotting, and solution hybridization assay were used to examine vasopressin-gene messenger ribonucleic acid (mRNA) transcripts in hypothalamic tissue from five strains of rats: Long-Evans, Wistar-Kyoto, and diabetes insipidus (Brattleboro) rats, spontaneously hypertensive-stroke-prone rats, and cross-bred diabetes insipidus x spontaneously hypertensive-stroke-prone rats. A 290 base-pair, single-stranded RNA probe, with 221 bases complementary to exon C of the vasopressin gene was synthesized by the SP6 transcription vector system. This probe labeled appropriate neurohypophysial hypothalamic neurons, as well as suprachiasmatic nucleus cells, in tissue samples from all five strains of rats. Confirming other recent hybridization results with diabetes insipidus rat brain tissue, diabetic animals were found to transcribe their mutated vasopressin gene. In addition, this investigation found that the cross-bred diabetic-hypertensive rat also synthesizes a vasopressin-gene messenger ribonucleic acid transcript. Quantitative analyses of solution and in situ hybridization results suggested the cross-bred diabetic-hypertensive rat exhibits a level of vasopressin-gene messenger ribonucleic acid similar to diabetes insipidus rats. This observation is consistent with previous data on the cross-bred diabetic-hypertensive rat which suggests they inherit the mutant vasopressin gene from Brattleboro rats.

Animals↗
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

Renal disease and the development of hypertension in salt-sensitive Dahl rats.

To elucidate the role of the kidneys in the development of hypertension in Dahl salt-sensitive (S), as compared to resistant (R) rats of the JR strain, we analyzed functional and morphological changes before and after the administration of an 8% NaCl diet and the onset of hypertension. The diet was begun at six weeks of age and was continued until 12 weeks of age. At six weeks, blood pressure was not different between S and R rats. Hypertension occurred in S rats receiving the 8% NaCl diet at week 8, and in S rats receiving 0.9% NaCl at week 10. Albuminuria and proteinuria were found in S rats prior to the 8% NaCl diet and progressed regardless of diet. Electron microscopy of glomeruli revealed segmental loss of epithelial foot processes in S rats at six weeks prior to the 8% NaCl diet. Mesangial widening, arteriolar myo-intimal cell hyperplasia and interstitial fibrosis occurred in all S rats. Inulin and PAH clearances in S rats decreased with time, the changes being accelerated by the 8% NaCl diet. Micropuncture of S and R rats prior to the 8% NaCl diet revealed no glomerular hypertension in S rats. The number of glomeruli in S and R rats were not different. We conclude that prehypertensive S rats of the JR strain already have albuminuric glomerular disease not associated with reduced number of glomeruli or glomerular hypertension. The renal pathology is accelerated once hypertension develops. A lower NaCl intake delays, but does not prevent renal disease in S rats.

Albuminuria↗
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

Induction of angiotensinogen mRNA in hepatocytes by angiotensin II and glucocorticoids.

In isolated rat hepatocytes, exposed to angiotensin II and glucocorticoids, angiotensinogen mRNA increased within 30-60 min, and angiotensinogen secretion with a time lag of about 2 hours. After 4 hours, angiotensinogen mRNA, estimated by liquid hybridization with radiolabeled cRNA, was 5.9 +/- 0.4 in control, and 10.8 +/- 0.8, 11.7 +/- 0.4, 16.1 +/- 0.8 and 21.7 +/- 0.2 pg/micrograms of total RNA in cells exposed to angiotensin II (9 nM and 90 nM), hydrocortisone (100 microM) and dexamethasone (10 microM) respectively. The corresponding secretion rates of angiotensinogen were 72 +/- 7, 124 +/- 4, 132 +/- 12, 220 +/- 19 and 217 +/- 18 fmol angiotensinogen/mg wet weight/hour. Thus, angiotensin II stimulates angiotensinogen synthesis and secretion by acting at a pretranslational site.

Angiotensin II↗
PubMed1988

Tissue renin-angiotensin systems aspects of molecular biology and pharmacology.

Advances in molecular biology over the last few years have made it possible to extend studies concerned with the role of renin in blood pressure regulation and fluid balance to the genetic level. Epidemiological data from cross-sectional population studies as well as experimental findings in spontaneously hypertensive rats suggest a greater disposition towards hypertension in males than in females. Testosterone (T) is known to raise blood pressure in female and castrated male SH-rats, while concomitantly increasing tissue renin activities. The availability of recombinant DNA technology and of a 32P labeled mouse submandibular gland renin cRNA as a hybridization probe enabled us to quantitatively assess whether this increase is paralleled by enhanced renin gene expression. In groups of female NMRI mice injected with DHT, we were able to show, that cardiac renin activity was significantly increased after 2 hours (1.6 fold) and 21 days (1.9 fold) of dihydrotestosterone (DHT) treatment compared to controls. DHT had no effect on renin mRNA concentration in the uterus, whereas in the ovary it resulted in a 50% decrease. We conclude that enhanced renin-activity and mRNA levels in peripheral organs and in the central nervous system are due to direct or indirect effects (cis, transacting) of T on renin gene expression. Thus, T may participate in the development of hypertension by stimulating the activity of tissue renin-angiotensin systems.

Animals↗
PubMed1988

Quantification of renin mRNA in various mouse tissues by a novel solution hybridization assay.

A new solution hybridization assay was established for the measurement of renin mRNA. The assay makes use of a radioactively labelled renin complementary RNA as hybridization probe and allows rapid and sensitive detection of renin mRNA in amounts as low as 0.5 pg. With this assay it was possible to quantify renin mRNA in tissues with low-gene expression such as brain and heart as well as in testis, kidney and the submandibular gland (SMG) of mice. The concentrations in these organs were 0.03, 0.07, 1, 5.2 and 164 pg renin mRNA/micrograms RNA, respectively. These results are in agreement with Northern blotting experiments. The general applicability and ease of the solution hybridization assay described here should greatly improve the rapidity of mRNA measurements in future functional studies.

Animals↗
PubMed1988

Angiotensin II controls angiotensinogen secretion at a pretranslational level.

It has been proposed that feedback by angiotensin II, the effector peptide of the renin-angiotensin system stimulates hepatic angiotensinogen synthesis, since long-term infusion of this octapeptide in vivo induced an increase in plasma angiotensinogen concentrations. In the present study, the effects of angiotensin II (9 and 90 nmol/l) on angiotensinogen messenger (m)RNA concentrations and on angiotensinogen secretion of freshly isolated rat hepatocytes were compared with those of glucocorticoids (hydrocortisone, 10(-4) mol/l, and dexamethasone, 10(-5) mol/l). Angiotensin II and the glucocorticoids elevated angiotensinogen mRNA concentrations two- to threefold. Angiotensinogen secretion rates were correspondingly increased with a time lag of about 2 h. Differences in the time-course of changes in mRNA following onset or decay of the hormonal effect suggest that angiotensin II and glucocorticoids express their effects by different intracellular mechanisms. This view is supported by the observation that angiotensin II but not dexamethasone has a stabilizing effect on angiotensinogen mRNA, when further synthesis was blocked by actinomycin D.

Angiotensin II↗
PubMed1988

Receptor autoradiographical evidence of a preferential reduction of binding sites for atrial natriuretic factor in renal papilla of the spontaneously hypertensive rat.

In the spontaneously hypertensive rat (SHR) as well as in the pathophysiological states with volume retention, high levels of atrial natriuretic factor (ANF) do not produce adequate diuresis and natriuresis. We have investigated the question whether the reduced effectiveness of ANF could be due to a reduction of the ANF binding. Evidence is provided by quantitative autoradiography with [125I]ANF than higher ANF plasma levels in SHRSP compared to normotensive WKY rats are associated with a reduced number of binding sites (25%) in the renal papilla as well as in the subfornical organ (69%). This could contribute to the reduced response of ANF in SHRSP.

Animals↗
PubMed1988

Substance P induces a cardiovascular defense reaction in the rat: pharmacological characterization.

In this study in conscious rats, we tested the hypothesis that substance P, a central pressor peptide and a potential transmitter substance of pain pathways, could be involved in the cardiovascular defense reaction that is typically associated with unpleasant sensory stimuli. The hemodynamic responses to centrally administered substance P were pharmacologically characterized. The increases in blood pressure and heart rate after intracerebroventricular injections of substance P were accompanied by mesenteric and renal vasoconstriction and hind limb vasodilation (pulsed-Doppler flow probes). The pressor and vasoconstrictor responses were attenuated by peripheral alpha 1-adrenoceptor blockade with prazosin but were not influenced by blockade of vascular vasopressin receptors with d(CH2)5Tyr(Me) arginine vasopressin (AVP). Cardiac beta 1-adrenoceptor blockade with metoprolol abolished the tachycardic and reduced the pressor responses. Substance P-induced hind limb vasodilation was not sensitive to intravenous atropine but was largely prevented by peripheral beta 2-adrenoceptor blockade with ICI 118,551. Thus, the substance P-induced pressor effects are mediated by alpha 1-adrenergic sympathetic vasoconstriction and beta 1-adrenergic cardiac stimulation, whereas the hind limb vasodilation is mainly due to beta 2-adrenergic stimulation. Substance P dose-dependently (0.01-10 micrograms i.c.v.) released oxytocin but not vasopressin or adrenocorticotropic hormone (ACTH) from the pituitary gland. High doses reduced basal ACTH levels. Together with the hemodynamic responses, a behavioral arousal reaction was observed, which included increased locomotion, grooming, scratching, and skin biting. Our results demonstrate that a neuropeptide can induce classic cardiovascular defense reaction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
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

Measurement of mRNA by solution hybridization with 32P-labelled single stranded cRNA probe ("SP6 test"). Comparison with a 32P-labelled single stranded cDNA as hybridization probe ("S1 test") for measurement of AVP mRNA.

Radioactively labelled cRNA for the rat AVP gene exon C was synthetized from a pSP64-vector and used for solution hybridization measurement of AVP mRNA ("SP6 test"). For comparison hybridization was carried out with a gel-purified radioactively labelled cDNA probe synthetized by primer extension of AVP gene exon C cloned into an M13mp9 phage vector DNA ("S1 test"). Both tests had a comparable sensitivity of up to 0.2 pg AVP mRNA. Under optimal hybridization conditions kinetics were similar in both tests. The fast and easy preparation of large amounts of labelled cRNA probe and simple determination of absolute amounts of mRNA by saturation kinetics without need of a mRNA standard makes the "SP6 test" an attractive alternative to the known "S1 test". The "SP6 test" should be applicable for a wide variety of genes.

Animals↗
PubMed1988

Vasopressin gene expression in hypertensive, normotensive, and diabetes insipidus rats.

This investigation examined the presence and abundance of vasopressin-gene messenger ribonucleic acid (mRNA) transcripts in hypothalamic tissue from five strains of rats: Long Evans, Wistar-Kyoto, and diabetes insipidus (Brattleboro) rats, stroke-prone spontaneously hypertensive rats, and cross-bred diabetes insipidus x stroke-prone spontaneously hypertensive rats. A single-stranded RNA probe complementary to exon C of the vasopressin gene was utilized for in situ hybridization and identified hypothalamic 'vasopressinergic' neurons in tissue from all five strains of rats. The results obtained by solution and in situ hybridization suggested the cross-bred diabetic-hypertensive rat exhibits a level of vasopressin-gene messenger ribonucleic acid similar to diabetes insipidus rats. This observation is consistent with previous physiological data which suggests cross-bred diabetic-hypertensive rats inherit the mutated vasopressin gene of the Brattleboro rat.

Animals↗
PubMed1988

Pre- and postsynaptic features of the central angiotensin systems. Indications for a role of angiotensin peptides in volume transmission and for interactions with central monoamine neurons.

The transmitter receptor matches and mismatches in the angiotensin (ANG) immunoreactive (IR) neuronal systems of the rat CNS have been characterized in various regions by means of ANG II immunocytochemistry and 125I-angiotensin II receptor autoradiography. By means of in situ hybridization the distribution of angiotensinogen mRNA has been mapped out and related to the distribution of ANG IR. In some areas, high densities of ANG IR nerve terminals and ANG II receptors (e.g. paraventricular hypothalamic nucleus, locus coeruleus and nucleus tractus solitarius) or high densities of ANG II receptors alone (e.g. medial geniculate body, subthalamic nucleus and superficial layer of the superior collicle) were often associated with high levels of angiotensinogen mRNA, suggesting the existence of an extracellular formation of ANG II, mediating biological responses. These results underline a role of ANG peptides in volume transmission in addition to transmitter function. Other areas, such as nuc. n. hypoglossi, practically lacking ANG IR terminals, pericarya and receptors, also contained high levels of angiotensinogen mRNA, suggesting a different role of angiotensinogen in these areas. Evidence for presynaptic (turnover changes) and post-synaptic (receptor-receptor crosstalk) interactions with CA neuronal systems has been obtained especially in cardiovascular centers. Thus, ANG II reduces in a concentration related way the affinity of 3H-paraminoclonidine binding sites in the dorsomedial medulla without influencing the Bmax value. These results indicate the existence of intramembrane interactions between ANG II and alpha 2 adrenergic receptors. Finally paraventricular but not perifornical ANG immunoreactive nerve cells costore nuclear glucocorticoid receptor IR, suggesting that some ANG neurons may be directly regulated by glucocorticoids.

Angiotensin II↗
PubMed1988

Renin gene expression in rat tissues: a new quantitative assay method for rat renin mRNA using synthetic cRNA.

A genomic renin exon 9 fragment was subcloned into vector pSPT18 and used for in vitro transcription to obtain 32P-labeled rat renin cRNA. Using this cRNA, we established quantitative solution hybridization and specific Northern blotting assays for renin mRNA. We were able to detect renin mRNA in the kidney, heart ventricle and atrium, brain, testis, and adrenal gland of male rats in the concentrations of 430 +/- 8.1, 110 +/- 1.9, 43 +/- 0.9, 64 +/- 1.1, 47 +/- 0.9 and 11 +/- 0.2 pg mRNA/mg of total RNA, respectively.

Animals↗