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T Unger

Publications and source records attributed to T Unger.

At least 271 records · Page 15Linked to original sources
PubMed1988

[The renin-angiotensin system: systemic and local function].

The renin-angiotensin system (RAS) has long been known as a hormonal system, which is important for the maintenance of volume homeostasis, and which contributes under certain circumstances to the pathogenesis of hypertension and cardiac failure. More recent findings have demonstrated that the individual components of this system can also be synthesized locally in tissue, e.g. in the brain, the vascular wall, the kidney, the adrenals, and the heart. Although the role of locally generated angiotensin within cardiovascular- and body volume regulation needs to be further investigated, it has already become clear that the mechanism of action of drugs interfering with the RAS is not confined to the circulating RAS, but also includes an interaction with local renin-angiotensin systems. These agents, particularly the converting enzyme inhibitors, have proved to be indispensible tools for elucidating the function of local renin-angiotensin systems, in addition to being therapeutically useful in the treatment of cardiovascular diseases.

Angiotensin II↗
PubMed1988

Measurement and characterization of angiotensin peptides in plasma.

We report a method for the extraction of angiotensin peptides from plasma with a mixture of acetone, 1 mol/L HCl, and water (40/1/5 by vol). The method is highly reproducible for the measurement of angiotensin I and angiotensin II in small sample volumes, with analytical recoveries of about 80% for both peptides. We investigated the influence of sample handling and found a standard procedure for blood collection, plasma preparation, and extraction was essential. The method was used to measure angiotensin I and II in rat and human plasma. In rat plasma, the mean (+/- SEM) concentrations of angiotensin I and angiotensin II were determined to be 67 (+/- 8) and 14 (+/- 1) pmol/L (n = 10), respectively. Neither angiotensin I nor angiotensin II was detectable 24 h after bilateral nephrectomy. Acute oral administration of the converting-enzyme inhibitor ramipril caused a significant increase of angiotensin I from 85 (+/- 6) to 257 (+/- 33) pmol/L (n = 10; P less than 0.001) and a significant decrease of angiotensin II from 12 (+/- 1) to 7 (+/- 0.4) pmol/L in rat plasma (n = 9; P less than 0.001). In human plasma, angiotensin I and angiotensin II values of 21 (+/- 1) and 6.6 (+/- 0.5) pmol/L (n = 10) were found. A single oral dose of the diuretic furosemide increased angiotensin I significantly from 21 (+/- 1) to 32 (+/- 1.7) pmol/L (n = 5); P less than 0.001), whereas angiotensin II remained unchanged, 6.6 (+/- 0.5) vs 6.4 (+/- 0.4) pmol/L (n = 5). Extracted peptides could be identified as [IIe5]-angiotensin I and [IIe5]-angiotensin II by HPLC in combination with specific radioimmunoassays for angiotensin I and angiotensin II.

Adult↗
PubMed1987

Effect of converting enzyme inhibitors on tissue converting enzyme and angiotensin II: therapeutic implications.

Local tissue renin-angiotensin systems have recently been discovered in various organs, and evidence is accumulating that inhibition of these local renin-angiotensin systems may contribute to the actions of converting enzyme (CE) inhibitors. Measurements of CE activity and angiotensin II concentrations revealed that after oral administration of CE inhibitors, CE was inhibited not only in lung vascular endothelium and blood, but also in the heart, kidney, vascular wall, brain and other organs. The functional significance of tissue CE inhibition is suggested first by the antihypertensive effect of brain CE inhibition in spontaneously hypertensive rats, second by the concomitant persistence of blood pressure decrease and CE inhibition in vascular wall and kidney after long-term oral CE inhibitor treatment and third by ex vivo experiments demonstrating marked effects of oral CE inhibitor pretreatment on cardiac function in isolated rat hearts. Local inhibition of tissue renin-angiotensin systems may be an important factor involved in the beneficial effects of CE inhibitors in such cardiovascular diseases as arterial hypertension, congestive heart failure and cardiac arrhythmias.

Administration, Oral↗
PubMed1987

Expression of the bcl-2 gene in mouse B lymphocytic cell lines is differentiation stage specific.

cDNA clones of mouse bcl-2 have been isolated and characterized by homology to the human bcl-2 gene, a putative oncogene that is found on the portion of chromosome 18 characteristically involved in the t(14;18) translocation present in nearly all human follicular B cell lymphomas. Our mouse cDNA clone detects 7.9 and 6.3-kb bcl-2 RNAs in mouse B cell lymphomas, but only in tumors consisting of pre-B and follicular center mature B cells, not in pro-B cell or plasma cell tumors. Thus, this gene appears to be a B cell differentiation marker that is expressed only in committed B cells, but is shut off in end stage plasma cells. This pattern of expression is unique among oncogenes, and we suggest that it may be responsible for the high frequency of translocations at this locus in the common malignancy of human mature B cells, follicular lymphomas.

Animals↗
PubMed1987

The renin-angiotensin system in the central control of blood pressure.

The results of biochemical, immunohistochemical and autoradiographic studies led to the description of the endogenous brain angiotensin II system as a highly localized network of angiotensin II-containing cell bodies and fibres as well as characteristic sites with high angiotensin II-receptor density. The specific localization of this system predominantly within limbic, hypothalamic and brain stem structures that are known to be involved in central cardiovascular regulation and the control of volume homeostasis, suggests a possible functional role for brain angiotensin II in the control of these homeostatic functions. A role for brain angiotensin II in the central control of blood pressure is further supported by physiological and pharmacological experiments that demonstrate characteristic central angiotensin-induced cardiovascular responses. However, it should be kept in mind that the mechanisms mediating these responses (e.g. sympathetic activation, vasopressin release), as well as the exact functional role of endogenously synthesized angiotensin II in specific brain areas, are not yet completely understood. Pathophysiologically, there is evidence that an activated brain renin angiotensin system may participate in the development and maintenance of primary hypertension.

Angiotensin II↗
PubMed1987

Release and regulation of atrial natriuretic peptide (ANP).

Mammalian atrial cardiocytes synthesize and secrete a hormone called atrial natriuretic peptide (ANP), which causes natriuresis, diuresis and inhibition of smooth muscle contraction, aldosterone and renin release. Volume loading, vasoconstrictor agents, immersion in water, atrial tachycardia and high salt diets have been reported to increase the release of cardiac ANP, thereby suggesting that the peptide is released in response to an increase in atrial pressure. That stretch is an important stimulus for ANP release is also suggested by clinical studies demonstrating a direct correlation between secretion rate and atrial pressure. The experiments using isolated perfused rat heart provide direct evidence that distension of the right atrium stimulates the release of ANP. Pharmacological studies in the isolated heart point to roles of cytosolic calcium, the phosphoinositide system and the cyclic AMP pathway in the regulation of ANP release. The concentration of calcium in heart muscle cells, in addition to the length of the muscle fibers, depends on many factors such as the action of humoral substances, cardiac nerve activity and heart rate, which may all contribute to the regulation of ANP secretion.

Acetylcholine↗
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

Atrial natriuretic peptide: a new factor in blood pressure control.

The hypothesis of a natriuretic factor-originally an intriguing possibility and now an experimentally documented reality-has occupied the minds of scientists for more than 30 years. It has attracted not only experts in salt and water metabolism but also those interested in hypertension, because of the well known link between sodium homeostasis and blood pressure regulation. There are at least two distinct types of natriuretic substances: one is an inhibitor of the Na+K+ATPase and has been proposed to contribute to a rise in blood pressure; the other, now isolated from atrial tissue, is vasodilatory, natriuretic, diuretic, and has been demonstrated to decrease blood pressure. Our knowledge of regulation and function of this ANP has increased rapidly since its detection. Its role in blood pressure regulation is now fairly well understood. As depicted in Fig. 1, both synthesis and release of ANP are induced by atrial and ventricular wall stretch. In hypertension, distension of the left atrium and ventricle may be of particular importance for ANP release. The endocrine function of myocardial cells is stimulated in response to wall stretch in the ventricle. ANP is synthesized and stored as a 126 amino acid prohormone. Enzymatic processing of this prohormone to the circulating forms ANP 1-98 and ANP 99-126 takes place within the myoendocrine cells. The biological effects of ANP 1-98 are as yet unknown. ANP 99-126 acts at multiple sites to reduce blood pressure. One may distinguish between acute and more chronic effects. The acute effects include shift of fluid to the extravascular compartment and vasorelaxation. This shift is indicated by the rapidly developing rise in haematocrit, which is observed in intact as well as in nephrectomized rats and therefore not due to diuresis alone. The reduction of blood volume in addition to an increase in venous capacitance may be responsible for the reduced cardiac output. The latter may cause a reflex activation of the sympathetic nervous system and an increase in peripheral resistance, thereby overriding the vasodilator effects of the peptide. ANP appears to have a 'de-pressor' effect rather than a direct vasodilator effect. A lowering of peripheral resistance in response to ANP is not observed in normotensives, but is readily seen in at least certain forms of hypertension associated with an increased vascular tone. This most likely explains the discrepancy in the haemodynamic responses to ANP in normotensives and hypertensives.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1987

Tissue renin-angiotensin systems: focus on the heart.

Recent findings support the existence of independently functioning, local renin-angiotensin systems in a number of tissues. The clinical importance that inhibitors of the renin-angiotensin system have gained in the treatment of hypertension and cardiac failure, as well as molecular biology data, suggest that a functional, tissue renin-angiotensin system is present in the heart. Using several experimental approaches we present evidence to support the existence and the possible physiopathological relevance of such a cardiac renin-angiotensin system. Tissue angiotensins were documented and quantified in different regions of the heart by high performance liquid chromatography combined with specific radio-immunoassay. Reduction of cardiac angiotensin after administration of converting enzyme inhibitors in nephrectomized animals indicates that these peptides are generated locally. Effects of converting enzyme inhibitors on angiotensin II-dependent facilitation of cardiac sympathetic tone further support this concept and emphasize the potential physiological role of a cardiac renin-angiotensin system. Further, direct evidence for local generation of angiotensin II in the myocardium is provided by assessment of the intracardiac conversion of angiotensin I to angiotensin II and by measurement of the activity of angiotensin converting enzyme in the heart.

Angiotensin II↗
PubMed1987

Interference with the autonomic nervous system by the converting enzyme inhibitor ramipril in conscious spontaneously hypertensive rats.

The interaction of the converting enzyme inhibitor (CEI) ramipril with sympathetic neurotransmission and the baroreceptor reflex (BRR) was investigated in conscious stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto (WKY) controls. Intravenous (i.v.) injection of ramipril (100 micrograms) attenuated the pressor responses to i.v. noradrenaline (NA) in SHRSP and WKY rats. Ganglionic blockade was performed with pentolinium (10 mg/kg i.v.), and blood pressure (BP) was subsequently supported with i.v. NA (1 microgram/min), angiotensin II (ANG II, 500 ng/min), or NA plus a subpressor dose (0.1 ng/min) of ANG II. Intravenous injection of ramiprilat (100 micrograms) significantly decreased NA-supported BP in SHRSP and WKY rats for more than 30 min, but did not lower BP in rats supported with ANG II or with NA plus a subpressor dose of ANG II. In SHRSP and WKY rats pretreated intracerebroventricularly (i.c.v.) with ramiprilat (0.5 microgram/min for 30 min), the slope of the BRR curve between increases in systolic BP and prolongation in pulse interval following bolus i.v. injections of methoxamine (10-100 micrograms/kg) was steeper than in vehicle-pretreated controls. In contrast, i.v. pretreatment with the same dose of the CEI did not increase BRR sensitivity. Our data in conscious animals demonstrate that CEI can interfere acutely with the autonomic nervous system through postsynaptic inhibition of neurotransmission and sensitization of the baroreceptor reflex. The relevance of this mechanisms for the chronic antihypertensive actions of CEI remains to be established.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1987

Central cardiovascular actions of vasopressin in the rat.

Arginine vasopressin (AVP) containing neurones and pathways have been localized in various cardiovascular control centers of the central nervous system in rats. AVP influences cardiovascular regulation when injected into various areas of the central nervous system. The blood pressure increases in response to central AVP injections were shown to be initiated by stimulation of central V1-AVP receptors and mediated by stimulation of sympathetic outflow to the periphery. On the other hand, AVP has also been shown to attenuate the pressor responses to electrical stimulation of the mesencephalic reticular formation when injected into the brain ventricular system. In addition, AVP can participate in cardiovascular regulation by modulating baroreceptor reflex sensitivity. We have shown that in rats peripheral (hormonal) AVP can sensitize the heart rate component of the baroreceptor reflex by acting on V2-AVP receptors accessible from the blood, while at the same time central (neuronal) AVP can attenuate the baroreceptor reflex through brain V1-AVP receptors that cannot be reached from the blood. Binding and functional studies favour the existence of V1-AVP receptors in the central nervous system, whereas evidence for central V2-AVP receptors is still scarce. The role of AVP in hypertension remains controversial, but recent evidence suggests that a discordance between the various central and peripheral cardiovascular actions of AVP, rather than its hormonal vasopressor effects, may contribute to the pathogenesis of hypertension.

Animals↗
PubMed1987

Tissue converting enzyme inhibition and cardiovascular effects of converting enzyme inhibitors.

Local renin-angiotensin systems have been described in organ controlling cardiovascular function. Following oral administration of converting enzyme (CE) inhibitors the enzyme was inhibited not only in lung vascular endothelium and blood, but also in the heart, kidney, vascular wall, brain and other organs. Evidence for a contribution of tissue CE inhibition to the cardiovascular actions of CE inhibitors is provided by the antihypertensive effect of brain CE inhibition in spontaneously hypertensive rats, by the concomitant persistence of blood pressure decrease and CE inhibition in vascular wall and kidney after chronic oral CE inhibitor treatment, and by the marked effects of oral CE inhibitor pretreatment on cardiac function in isolated rat hearts. Local inhibition of tissue renin-angiotensin systems may therefore be an important factor involved in the beneficial effects of CE inhibitors in cardiovascular diseases such as arterial hypertension, congestive heart failure, and cardiac arrhythmias.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1987

Dissociation between heart rate and sympathetic nerve responses to baroreceptor activation in spontaneously hypertensive rats.

We tested the baroreflex in conscious, stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto controls (WKY) with incremental bolus injections of nitroprusside and methoxamine. The change in heart rate (HR) per change in mean blood pressure (MAP) was greater in WKY than in SHRSP. In contrast, the change in splanchnic nerve activity (SpNA) per change in MAP was greater in SHRSP than in WKY. The sympathetic outflow in SHRSP seems more reactive to blood pressure changes than in WKY. The discordance in HR and SpNA changes suggests that the integration of autonomic function in SHRSP is impaired.

Animals↗
PubMed1987

Brain angiotensin II: localization and possible functions.

The results of biochemical, immunohistochemical and autoradiographic studies have led to the description of the endogenous brain angiotensin II system as a highly localized network of angiotensin II-containing cell bodies and fibers as well as characteristic sites with high angiotensin II receptor density. The specific localization of this system predominantly within limbic, hypothalamic and brain stem structures that are known to be involved in central cardiovascular regulation and the control of volume homeostasis suggests a possible functional role of brain angiotensin II in the control of these homeostatic functions. In particular, brain angiotensin II may function to help maintaining adequate tissue perfusion to vital parts of the body at times, when body fluid and cardiovascular homeostasis are jeopardized. In addition, there is evidence that brain angiotensin II may participate in the control of hormone release from the anterior and posterior pituitary gland, regulation of body temperature and the processing of learning contents. Future research may profitably be directed towards an exact functional characterization of central angiotensinergic pathways as well as an detailed analysis of the mechanisms that underly central angiotensin II-induced responses.

Angiotensin II↗
PubMed1986

[Hypertension].

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Combined Modality Therapy↗