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Biomedical subjects

D Ganten

Publications and source records attributed to D Ganten.

At least 271 records · Page 15Linked to original sources
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↗
PubMed1991

Local angiotensin formation in hindlimbs of uremic hypertensive and renovascular hypertensive rats.

To examine and characterize the vascular renin--angiotensin system in low-renin models of renal hypertension with and without the presence of overt renal insufficiency, we studied the formation and metabolism of angiotensin in isolated perfused rat hindquarter preparations. Rats with 5/6 nephrectomy (5/6NX) and rats with one-kidney, one clip (1K1C) hypertension were compared to sham operated (sham) animals. Angiotensin peptides in plasma or perfusate were characterized by high-performance liquid chromatography and radioimmunoassay (RIA). Plasma angiotensin II was lower, and blood pressure was higher in both experimental groups, compared to sham animals. Plasma angiotensinogen, measured by both direct and indirect RIA, was increased in both experimental groups. The spontaneous release of angiotensin I and angiotensin II from perfused hindquarters did not differ between the groups. Angiotensin I conversion was not different in 5/6NX or 1K1C groups compared with controls. Furthermore, angiotensin conversion was completely inhibited by captopril (1 mumol/l) in all groups. Renin-induced angiotensin release was significantly increased in 5/6NX as compared with sham rats, whereas there was no difference in renin-induced angiotensin release between 1K1C and sham animals. Angiotensin II degradation was significantly attenuated in 5/6NX rats when compared with sham rats (27.6% versus 53.9%, respectively, P less than 0.05) but was unaltered in 1K1C rats. Thus, in chronic uremic hypertension, renin-induced angiotensin formation was increased in the face of decreased angiotensin II degradation. These data suggest that vascular angiotensin may contribute to the elevated blood pressure observed in chronic renal failure. In 1K1C rats, vascular angiotensin formation and metabolism was unchanged despite suppressed plasma angiotensin II.

Angiotensin II↗
PubMed1991

The cardiac renin-angiotensin system: a synopsis of current experimental and clinical data.

Local tissue-resident renin-angiotensin systems are increasingly being recognized as important neurohumoral mediators which may act in concert with, but also independently of the circulating system. Here we review the evidence supporting the existence, functional integration, and physiopathological role of a cardiac renin-angiotensin system which has recently been defined. The elements of the catalytic cascade of the system, renin, angiotensinogen, and angiotensin-converting enzyme have all been demonstrated in cardiac tissues, both on the protein-level and with regard to local expression of the respective genes. Modulation of gene expression in response to various perturbations has been demonstrated, and may occur independently of the plasma or other tissue renin-angiotensin systems. In isolated hearts, generation of the biologically active peptides, angiotensin I and II, has been documented, establishing the capability of this system to act as an independently regulated, functionally integrated catalytic pathway for the production of angiotensin II. Through specific receptors, present in the heart as in other tissues, angiotensin mediates profound effects on cardiomyocyte function and, as we are beginning to learn, on structure and growth. Furthermore, indirect evidence based on specific, beneficial effects of angiotensin converting enzyme inhibiting drugs which are distinct from those of other vasodilators, points to the potential role which this local system may play for physiological function of the heart as well as in a number of pathological derangements of the cardiovascular system.

Angiotensin II↗
PubMed1990

Autoradiographic localization of mas proto-oncogene mRNA in adult rat brain using in situ hybridization.

The cellular localization and the distribution of the mas proto-oncogene/angiotensin receptor mRNA have been studied in the male rat brain using in situ hybridization with radiolabelled mas cRNA probes. Neuronal cell populations in the forebrain were selectively labelled. A strong specific labelling was demonstrated in the dentate gyrus, the CA3 and CA4 areas of the hippocampus, the olfactory tubercle (medical part), the piriform cortex and the olfactory bulb, while a weak to moderate labelling was present all over the neocortex and especially in the frontal lobe.

Animals↗
PubMed1990

Evidence for the existence of angiotensin II like immunoreactivity in subpopulations of tyrosine hydroxylase immunoreactive neurons in the A1 and C1 area of the ventral medulla of the male rat.

By using double immunolabelling techniques the possible coexistence of tyrosine hydroxylase (TH)- and angiotensin II (ANG II)-like immunoreactivities (IR) has been studied within the noradrenaline A1 and adrenaline C1 areas of the ventral medulla of the rat. In the A1 area 20-30% of the TH IR nerve cell bodies were ANG II IR and in the C1 area 5-40% of the TH IR nerve cell bodies displayed ANG II IR. These results suggest the existence of ANG II/NA and ANG II/A costoring neurons in the A1 and C1 group, respectively, opening new possibilities for ANG II-catecholamine interactions in cardiovascular and neuroendocrine regulation.

Animals↗
PubMed1990

Fulminant hypertension in transgenic rats harbouring the mouse Ren-2 gene.

PRIMARY hypertension is a polygenic condition in which blood pressure is enigmatically elevated; it remains a leading cause of cardiovascular disease and death due to cerebral haemorrhage, cardiac failure and kidney disease. The genes for several of the proteins involved in blood pressure homeostasis have been cloned and characterized, including those of the renin-angiotensin system, which plays a central part in blood pressure control. Here we describe the introduction of the mouse Ren-2 renin gene into the genome of the rat and demonstrate that expression of this gene causes severe hypertension. These transgenic animals represent a model for hypertension in which the genetic basis for the disease is known. Further, as the transgenic animals do not overexpress active renin in the kidney and have low levels of active renin in their plasma, they also provide a new model for low-renin hypertension.

Adrenal Glands↗
PubMed1990

Vasopressin mRNA in the neurolobe of the rat pituitary.

Pro-vasopressin-neurophysin mRNA (AVP mRNA) was assayed in the pituitary gland of rats from different strains, using a specific cRNA probe corresponding to exon C of the vasopressin gene. Northern blot analysis revealed the presence of an about 650 base pair (bp) AVP mRNA in the neurolobe of all strains. No signal was found in the anterior or intermediate lobes. Partial nucleotide sequence analysis suggested identity with the genuine AVP mRNA. Osmotic stimulation with 2% saline or water deprivation increased AVP mRNA levels in a fashion that paralleled changes seen in the hypothalamus. The origin of the AVP mRNA in the neurolobe is uncertain but is likely to be the pituicytes. Transport of the mRNA into the nerve endings of hypothalamic supraoptic and paraventricular neurons is an alternative possibility.

Animals↗
PubMed1990

[Pathophysiology of the renin-angiotensin system].

The renin angiotensin system is an important system for the regulation of blood pressure and salt and water homeostasis. As a pathogenetic factor it is involved in the development of several forms of renal hypertension and, furthermore, it participates in the pathogenesis of primary and secondary hypertension. The regulation of the activity of the system is under the control of neuronal and hormonal mechanisms and depends on blood pressure and plasma concentrations of sodium chloride. With the development of converting enzyme inhibitors and their vasodilator, diuretic and sympatholytic actions a new important antihypertensive principle for lowering blood pressure was found. In this context also local renin angiotensin systems which have been described for several tissues have to be discussed as a possible target of action for converting enzyme inhibitors.

Acute-Phase Reaction↗
PubMed1990

Detection of vasopressin mRNA in the neurointermediate lobe of the rat pituitary.

A messenger ribonucleic acid (mRNA) homologous to the transcript that encodes vasopressin (VP) was detected in the neurointermediate lobe (NIL) of the rat pituitary. The abundance of this transcript is approximately 1/100th the amount detected in the hypothalamus. In rats drinking 2% NaCl-water for 0,2,4, or 10 days, or for 10 days and then tap water for 14 days, the levels of VP mRNA in the NIL were altered in a fashion that paralleled changes in the hypothalamus.

Animals↗
PubMed1990

Peptidergic control of cardiovascular function: the angiotensin paradigm.

If we consider the chemical messengers in the central nervous system, there are about ten classic transmitters--the catecholamines, biogenic amines and amino acids--as opposed to over 50 different neuropeptides. These include previously well-established circulating hormones such as angiotensin, atrial natriuretic peptide, vasopressin and oxytocin, calcitonin and calcitonin gene related peptide (CGRP), the opioid family of peptides, gastrointestinal peptides, pituitary peptides and their releasing factors, and miscellaneous peptides such as the kinins, bombesin, gallanin, and others; all occur as neuropeptides in the brain. There is evidence supporting a role in central cardiovascular control for angiotensin, opioid peptides, substance P, neuropeptide Y, vasopressin, atrial natriuretic peptide, kinins, corticotropin releasing factor, bombesin, somatostatin, and some other peptides. They have been localized in brain areas known to be important for blood pressure regulation, and specific high-affinity peptide receptors have also been discovered. Upon central administration, these peptides produce cardiovascular effects, partly by interacting with other blood pressure-controlling neuroregulators, e.g. catecholamines and GABA. Central inhibition of brain peptide synthesis or interaction with competitive antagonists at the receptor site results in marked cardiovascular effects. Altered peptide levels and activity of synthesizing enzymes, as well as supersensitivity to the pressor action of some brain peptides, have been described in experimental models of hypertension. We are using angiotensin as a model peptide to study the peptidergic control of cardiovascular function.

Brain↗
PubMed1990

The role of tissue renin-angiotensin systems in hypertension and effects of chronic converting-enzyme inhibition.

When inhibitors of the renin-angiotensin system (RAS) were initially developed, they were believed to act as antihypertensive agents mainly under pathophysiological conditions, in which an elevated plasma RAS contributed to the elevation and maintenance of high blood pressure (BP). However, evidence has accumulated from studies in hypertensive patients, as well as in animals, indicating that BP could be lowered by converting-enzyme inhibitors (CEIs) independently of whether or not the plasma RAS was stimulated. Several other effects had to be considered. It was thus discovered that converting enzyme (CE) is identical with the bradykinin-degrading enzyme, kininase II, and CEIs can therefore potentiate the vasodepressor effects of bradykinin and thereby interact with the prostaglandin system. Actions of CEIs possibly unrelated to inhibition of angiotensin and kininase also need to be considered. The actions of CEIs at the tissue level (brain, heart, blood vessels, kidney, adrenal gland) and their interference with the autonomic nervous system through central and peripheral actions may under certain conditions be more important than their inhibition of the circulating hormonal plasma angiotensin II. Recent clinical and experimental studies and new insights in the molecular biology of the RAS, especially gene expression of renin and angiotensinogen in tissues of the cardiovascular system, support this view. We have found that chronic CE inhibition with substances such as captopril, quinapril and lisinopril specifically affects angiotensinogen mRNA levels in cardiovascular tissues, and has marked effects on left ventricular hypertrophy, possibly through an action on cardiac angiotensin. These findings have consequences not only for the understanding of pharmacokinetics and pharmacodynamics of CEIs but also for their practical therapeutic use.

Adrenal Glands↗
PubMed1990

Androgen dependence and tissue specificity of renin messenger RNA expression in mice.

Testosterone, a steroid hormone which increases blood pressure by hitherto unknown mechanisms, is known to induce renin synthesis in the submandibular gland (SMG) of mice. Since renin as well as all other components of the renin-angiotensin system are present in organs important for cardiovascular control, e.g. the kidney, heart, adrenal gland and brain, it is of interest to study the effect of testosterone on renin gene expression in these organs. Renin messenger (m) RNA concentrations were measured by a solution hybridization assay using a 32P-labeled mouse SMG renin complementary (c) RNA as a radioactive probe (detection limit: 1 pg renin mRNA). Measurements were performed after 2 h and after 2, 7, 14 and 21 days of dihydrotestosterone (DHT) treatment in female NMRI mice. Renin mRNA concentration (values are expressed as pg renin mRNA/ micrograms total RNA) in the SMG was significantly increased after 7 days (108 +/- 22 in controls versus 630 +/- 101 in DHT-treated mice), after 14 days (83 +/- 15 in controls versus 743 +/- 83 in DHT-treated mice) and after 21 days (107 +/- 30 in controls versus 579 +/- 76 in DHT-treated mice), but did not reach levels found in untreated male NMRI mice (1021 +/- 84). In the kidney, a decrease was observed within 21 days, from 43 +/- 4 and 40 +/- 4 to 29 +/- 2 and 22 +/- 1.7 pg/micrograms in controls and DHT-treated groups, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗
PubMed1990

Structural alterations of the renin gene in stroke-prone spontaneously hypertensive rats: examination of genotype-phenotype correlations.

Primary hypertension is considered a polygenic, inherited disorder; to date, the nature of the genes involved remains unknown. In this study we present evidence for a structural difference in the gene coding for renin between the stroke-prone, spontaneously hypertensive rat (SHRSP) and its normotensive control, the Wistar-Kyoto rat (WKY). Restriction fragment analysis using hybridization against probes complementary to defined regions of the renin gene identified a deletion, approximately 700 base pair in size, within the first intron in SHRSP compared with WKY. This restriction fragment length polymorphism (RFLP) affects a part of the gene that is characterized by the presence of a multimeric tandem repeat element, where the occurrence of insertional/deletional events might be expected and have recently been shown in other rat strains. In order to test for a possible phenotypical representation of this RFLP, we studied a population (n = 115) of F2 hybrid rats derived from cross-breeding SHRSP with WKY. Using direct blood pressure measurements in conscious animals, we ruled out a cosegregation of systolic or diastolic blood pressure with renin genotype. Several other phenotypical parameters examined (heart rate, absolute and relative magnitude of changes in blood pressure induced by stress or dietary sodium loading, plasma renin activity, ventricular hypertrophy and tissue water content) also showed no cosegregation with genotype. Our findings are in contrast to a recently published study examining an RFLP of the renin gene distinguishing salt-sensitive and salt-resistant Dahl rats. Thus, cosegregation of genotype and phenotype are not consistent, although in both cases, structural differences in the same region of the renin gene separate the hypertensive strain from its normotensive controls. These data may suggest differential roles of the renin-angiotensin system in these two models of genetically predetermined hypertension.

Animals↗