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K Amann

Publications and source records attributed to K Amann.

At least 91 records · Page 5Linked to original sources
PubMed1996

[Permissive effect of PTH on vascular wall hypertrophy of intramyocardial arteries in experimental renal failure].

BACKGROUND: Abnormalities in cardiovascular structure e.g. LV hypertrophy and thickening of vessels (elastic and peripheral arteries, veins) are hallmarks of renal failure. Among other hormones parathyroid hormone (PTH) has been shown to affect cardiac function and has also been identified at a permissive factor for the activation of the cardiac interstitium leading to myocardial fibrosis. The present study was designed to examine whether PTH was also permissive for intramyocardial arteriolar wall thickening in an experimental model of renal failure. MATERIAL AND METHODS: Sham operated or subtotally nephrectomized rats (SNX) were parathyroidectomized (PTX) and received either saline or rat 1,34 PTH by osmotic minipump. After perfusion fixation, intramyocardial arterioles were assessed using stereological techniques (wall thickness, wall/lumen ratio, minimal lumen diameter, length density). RESULTS: Wall thickness of intramyocardial arterioles was significantly higher in SNX than in sham-op controls. SNX-PTX animals receiving solvent did not differ from sham-op controls while SNX-PTX animals receiving PTH had increased values which were comparable with those of SNX. In addition, PTH treated animals showed signs of marked vascular smooth-muscle cell and endothelial cell activation. CONCLUSIONS: The data suggest that intramyocardial arteriolar wall thickening in experimental renal failure and probable changes of vessel architecture in renal insufficiency in general are dependent upon the permissive effect of PTH.

Animals↗
PubMed1996

Cardiac structure and function in renal disease.

Cardiac death secondary to ischaemia, but not necessarily associated with coronary lesions, is the leading cause of death in uraemic patients. This article reviews recent findings that demonstrate abnormalities of cardiac structure which have a bearing on ischaemia tolerance. These abnormalities comprise the following: (1) left ventricular hypertrophy not fully explained by increased mean arterial pressure, (2) interstitial fibrosis and (3) abnormalities of myocardial microvasculature, i.e. capillary rarefaction and arteriolar-wall thickening.

Endomyocardial Fibrosis↗
PubMed1996

Arteriolar wall thickening, capillary rarefaction and interstitial fibrosis in the heart of rats with renal failure:the effects of ramipril, nifedipine and moxonidine.

In experimental renal failure, increased intramyocardial arteriolar wall thickness, reduced myocardial capillary density, and increased cardiac interstitium are found. The extent to which such alterations can be modified by therapeutic interventions has not been investigated to date. The purpose of this study was to examine the effects of Ramipril, Nifedipine and Moxonidine on these structural changes. Sham-operated and subtotally nephrectomized (SNX) 300-g male Sprague-Dawley rats (N = 7 to 11) were left untreated (N = 9) or treated with Ramipril (0.5 mg/kg body wt per day; N = 7), Nifedipine (30 mg/kg body wt per day; N = 9), or Moxonidine (10 mg/kg body wt per day; N = 8) for 8 wk. After perfusion fixation, heart and aorta were examined by stereological techniques. Aortic wall thickness was significantly higher in SNX than in sham-operated control rats and was similarly lowered by all three interventions. In contrast, the wall thickness of intramyocardial arterioles was significantly higher in SNX; this was prevented by Ramipril and Nifedipine, but not by Moxonidine. Intramyocardial capillary length density (Lv) was significantly lower and interstitial volume density (Vv) significantly higher in untreated SNX. Reduction of capillary length density was completely prevented by Moxonidine and in part by Ramipril. The increase in cardiac interstitial volume density was completely prevented by Ramipril and was partially prevented by Moxonidine or Nifedipine treatment. The following conclusions can be drawn from the results: (1) all agents normalize aortic wall thickness, but only calcium channel blockers and angiotensin-converting enzyme (ACE) inhibitors prevent intramyocardial arteriolar wall thickening: (2) intramyocardial arteriolar wall thickening, capillary rarefaction, and expansion of the cardiac interstitium are seen in SNX even after lowering the blood pressure to subnormal levels; i.e., changes in systemic blood pressure cannot completely explain the altered vascular structure in renal failure; (3) the effects of Ramipril, Nifedipine, and Moxonidine on cardiovascular structures in experimental renal failure are not completely accounted for by their hemodynamic actions.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

Influence of specific and non-specific endothelin receptor antagonists on renal morphology in rats with surgical renal ablation.

BACKGROUND: Studies in experimental models of chronic renal failure suggest an important role for the endothelin system in the development of renal scarring. Endothelin receptor (ETR) anatagonists interfere with progression, but it has not been resolved (i) whether this is true for all models of renal damage, (ii) to what extent the effect is modulated by systemic blood pressure and (iii) whether the effect is similar for ETAR and ETA/ETBR antagonists. STUDY DESIGN: 5/6 subtotal nephrectomy (SNX) by surgical ablation in male Sprague-Dawley rats. Comparison of ACE inhibitor Trandolapril (0.1 mg/kg/day), ETAR antagonist BMS 182874 (30 mg/kg/day) and ETAR/ETBR antagonist Ro 46-2005 (30 mg/kg/day) by gavage. Duration of the experiment eight weeks. METHODS: Systolic blood pressure by tail plethysmography. Perfusion fixation of kidneys and morphometric analysis ET-1 and ETA/ETBR by quantitative PCR. RESULTS: SNX caused a significant (P < 0.01) increase of systolic blood pressure (170 +/- 8.6 mmHg) compared to sham operated controls (131 +/- 5.3 mmHg). Blood pressure was significantly (P < 0.001) lower with Trandolapril (128 +/- 5.3 mmHg), but not with BMS 182874 (153 +/- 5.9 mmHg) or Ro 46-2005 (167 +/- 7.6 mmHg). Compared to sham operated rats (0.03 +/- 0.01) glomerulosclerosis index (GSI) was significantly (P < 0.01) higher in the untreated SNX group (0.9 +/- 0.15). Significantly lower GSI was found in Trandolapril treated (0.29 +/- 0.04), BMS 182874 treated (0.36 +/- 0.05), and Ro 46-2005 treated animals (0.45 +/- 0.11). The effect of BMS 182874 was accompanied by lower tubulointerstitial damage index. Mean glomerular volume was dramatically increased (P < 0.001) in SNX rats as compared to sham operated animals. This glomerular enlargement was partially prevented by Trandolapril (P < 0.05), but not by either ETR antagonist. ET-1 mRNA tended to be higher in SNX irrespective of treatment, while ETAR and ETBR mRNA were significantly lower. CONCLUSION: Both specific (ETAR) and non-specific (ETA/ETBR) endothelin antagonists interfere with development of glomerulosclerosis by mechanisms which are, at least in part, independent of systemic blood pressure.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

Effect of ramipril, nifedipine, and moxonidine on glomerular morphology and podocyte structure in experimental renal failure.

BACKGROUND: Experimental renal failure causes structural alterations of the kidney. It is still unresolved how these changes are modified by antihypertensive treatment. Purpose of the study. To examine the effects of different antihypertensive agents (ramipril, nifedipine, moxonidine) mainly on glomerular geometry, cell number, cell morphology, and capillarization, in a subtotal nephrectomy model of renal failure. MATERIAL AND METHODS: Sham-operated male SD rats and subtotally nephrectomized (SNX) ad libitum-fed rats were examined. Groups of 8-10 SNX rats were left untreated or were treated with ramipril (0.5 mg/kg b.w. per day), nifedipine (20 mg/kg b.w. per day) or moxonidine (10 mg/kg b.w.per day) respectively. After perfusion fixation the kidneys were examined using stereological techniques. RESULTS: Systolic blood pressure (by tail plethysmography) was 110+/-13 mm Hg in sham-op and 119+/-9 in SNX. It was effectively and comparably reduced below normal values by ramipril (89+/-11 mmHg), nifedipine (98+/-23 mmHg) and moxonidine (92+/-11 mmHg). The glomerulosclerosis index (SI) was significantly increased in SNX versus sham-op; it was similarly decreased by ramipril and moxonidine but less so by nifedipine. Vascular damage (preglomerular vessels) was reduced by all treatments whereas tubulointerstitial damage was signficantly reduced only by ramipril and moxonidine. Mean glomerular tuft volume was increased in SNX compared to sham-op. controls and was normalized only by ramipril treatment. Glomerular cells were differentially affected the three antihypertensive agents. After subtotal nephrectomy an increase in podocyte volume and mesangial cell number per glomerulus was noted. Nifedipine, and to a lesser extent ramipril, prevented mesangial cell hyperplasia. In contrast, only the ACE inhibitor ramipril, but not nifedipine or moxonidine prevented podocyte abnormalities, particularly podocyte hypertrophy. CONCLUSIONS: (i) Despite comparable reduction in systolic blood pressure, different classes of antihypertensive agents had diverse effects on renal damage in subtotally nephrectomized rat. This observation is consistent with specific, non-hemodynamic actions of anti-hypertensives. (ii) Glomerular and tubulointerstitial damage are prevented by treatment with ACE inhibitors and antisympathotonic agents, but not with the calcium antagonist nifedipine. In contrast, renal vascular changes were also prevented by nifedipine. (iii) Only ACE inhibitors effectively inhibited podocyte hypertrophy and mesangial cell hyperplasia. Whether the superior effect of ACE inhibitors on glomerulosclerosis is related to inhibition of glomerular growth and podocyte hypertrophy as well as preservation of podocyte structure, or whether these findings are merely a passive reflection of greater efficacy, remains unresolved.

Animals↗
PubMed1995

Effects of ibogaine on sensory-motor function, activity, and spatial learning in rats.

Ibogaine, a naturally occurring alkaloid, has been show to reduce naloxone-precipitated withdrawal symptoms from morphine. Given the clinical possibilities, it is important to determine ibogaine's effects on sensory-motor function, activity, learning, and memory. Long-Evans rats injected with doses of 20-60 mg/kg of ibogaine displayed slower response times on sensory and sensory-motor tests and were impaired in performing specific motor reflexes at doses of 40-60 mg/kg. Furthermore, these rats showed a marked reduction in locomotor and nonlocomotor activity, as well as emotionality at doses ranging from 10-40 mg/kg. At the higher doses the rats appeared to be virtually inactive. There were also deficits in learning a spatial location task (a dry-land version of the Morris water-maze). The deficits, however, were probably due to a reduction in locomotor activity and reduction in detection of sensory information. In a final experiment, a single injection of 40 mg/kg of ibogaine had marked deleterious effects on the acquisition of the spatial location task 1 but not 7 days after the injection, even though in this case there were no effects on sensory motor function 1 or 7 days after the injection. Thus, there are severe sensory-motor activity and learning problems while the animal is under the influence of ibogaine (acute effect) as well as long-term consequences on learning without concomitant changes in sensory-motor function.

Animals↗
PubMed1995

Changes of vascular architecture independent of blood pressure in experimental uremia.

Striking alterations of the structure of arterial vessels of different caliber are a well-known feature of renal failure, but it is currently unknown to what extent they are a reflection of hypertension or of uremia per se. To address this issue further we studied subtotally nephrectomized rats, sham-operated and pair-fed with matched controls. After uremia of 14 days' duration, stereologic measurements were carried out on perfusion-fixed tissue. To eliminate a potential influence of hypertension, subgroups of animals received furosemide and hydralazine in the drinking fluid to yield daily doses of 15 mg/kg and 20 mg/kg, respectively. At the end of the experiment, systolic blood pressure (tail plethysmography) was 110 +/- 13.3 (mean +/- SD) mm Hg and 99.4 +/- 8.1 mm Hg in untreated and treated controls, respectively, and 132 +/- 20.7 mm Hg and 103 +/- 13.0 mm Hg in untreated and treated uremic animals, respectively (n = 5 to 10 animals per group). The wall:lumen ratio of intramyocardial small arteries was 0.056 +/- 0.011 and 0.052 +/- 0.006 in untreated and treated controls, respectively. In untreated and treated uremic animals, the corresponding values were 0.077 +/- 0.011 and 0.066 +/- 0.007 (P < .01; control v uremia, ANOVA). A similar increase, unaffected by blood pressure treatment, was found for wall thickness of intramyocardial arteries. Analogous changes were also noted in mesenteric arterioles and veins. Finally, aorta media thickness was significantly (P < .005) higher in uremic animals than in controls (138 +/- 29 micrometers v 103 +/- micrometers).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Cardiocirculatory effects of acutely increased intracranial pressure and subsequent brain death.

Hemodynamic instability and functional impairment of the donor heart are currently reported problems in organ transplantation. Actual shortage of potential donor hearts continues to raise controversial discussion about adequate donor management with regard to graft quality. In an experimental open chest model, physiopathologic effects of acutely induced, irreversible intracranial hypertension (AIIHT) were investigated in situ with respect to hemodynamics, cardiac pump and muscle function, and hormonal parameters. Acutely induced irreversible intracranial hypertension was induced by rapid inflation of a subdural balloon catheter in 10 anesthetized dogs, four animals serving as controls. The observation period in both groups was 300 min. Cardiocirculatory stability was maintained by continuous crystalloid volume substitution without the use of inotropic or pressor agents. After AIIHT, three characteristic hemodynamic response phases have been observed: 1) The "acute hyperdynamic phase" lasting up to 15 min with marked increases of heart rate (HR), left ventricular pressure (LVP), cardiac output (CO) and myocardial contractility indices, 2) At the end of the "early restabilization phase", (60 min), these parameters returned close to control levels, except HR (+50%) and systemic vascular resistance (SVR) (-40%), 3) During the "late restabilization phase", filling pressures, LVP and CO remained within control limits at low SVR, contractility indices showed a decreasing tendency. All assessed plasmatic hormones (Catecholamines, triiodothyronine (T3), thyroxine (T4), adrenocorticotropic hormone (ACTH), cortisol and anti-diuretic hormone (ADH) showed a continuous fall to levels significantly below control over the phases of restabilization. Acutely induced irreversible intracranial hypertension leads to multifactorial hemodynamic and hormonal changes. At low SVR, cardiac pump function was preserved exclusively by continuous volume substitution, while myocardial contractility indicated a slight decrease. From this observed hemodynamic and functional state within the donor organism, no reliable prediction on graft functional capacity can be made.

Animals↗
PubMed1995

Preservation of myocardial blood flow by calcium antagonists does not prevent attenuation of regional myocardial function after repetitive brief periods of myocardial ischaemia in the rat heart.

The aim of this study was to assess the effect of two different calcium channel blockers on myocardial blood flow and function in a rat model of myocardial 'stunning' by repeated short episodes of ischaemia ('repetitive ischaemia'). In an open chest rat model, the left anterior descending coronary artery was ligated for 10 min followed by 15 min reperfusion. In total, five periods of ischaemia and reperfusion were performed. Myocardial blood flow was assessed by the hydrogen clearance technique and systolic thickening fraction by pulsed Doppler. After five episodes of ischaemia, myocardial blood flow adn myocardial thickening in the ischaemic area were reduced by 60 +/- 8% and 52 +/- 7% (n=9), respectively, as compared to baseline. Continuous intravenous infusion of the calcium channel blockers nifedipine (n=6) and gallopamil (n=6), started 20 min prior to onset of ischaemia, attenuated the ischaemia-induced decrease of myocardial perfusion. Nifedipine was the most effective with only 5 +/- 2% reduction in blood flow after five ischaemic episodes, whereas reduction of myocardial blood flow was 30 +/- 4% in the presence of gallopamil. However, neither nifedipine nor gallopamil were able to prevent regional ventricular dysfunction induced by repetitive ischaemia. Despite the preservation of myocardial blood flow following repetitive ischaemia, calcium channel blockers do not prevent ischaemia-induced reduction of myocardial function in the ischaemic area.

Animals↗
PubMed1995

Hypertrophy and hyperplasia of smooth muscle cells of small intramyocardial arteries in spontaneously hypertensive rats.

Hearts of stroke-prone spontaneously hypertensive rats (SHR) were investigated by means of stereology and were compared with those of normotensive. Wistar-Kyoto controls. At the age of 9 months, hypertensive rats showed cardiac hypertrophy, marked myocardial fibrosis, activation of nonvascular interstitium, focal myocytial degeneration, reduction of capillarization, and microarteriopathy of small intramyocardial arteries. Stereologically, a significant increase in the total left ventricular arterial wall volume (+180% versus controls) was found in SHR hearts. By using new stereological techniques, the orientator and the nucleator, we investigated whether this significant increase in total left ventricular arterial wall volume was due to hyperplasia of smooth muscle cells in addition to the process of vascular smooth muscle cell hypertrophy that is common in SHR. Additionally, the nuclear size and ratio of cell volume to nuclear volume were determined using another new stereological technique, the selector. The stereological data indicate a significant increase in mean cell and nuclear volumes as well as in the total number of left ventricular arterial smooth muscle cells of SHR. Additionally, the total length of intramyocardial arteries was also significantly increased in hypertensive rats. The volume and number of arterial smooth muscle cells per arterial length were significantly (P < .001 and P < .05, respectively) higher in SHR than in normotensive controls. Thus, we conclude that hypertrophy and hyperplasia of smooth muscle cells are involved in intramyocardial arterial growth processes in hypertensive heart remodeling.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Blood-pressure-independent wall thickening of intramyocardial arterioles in experimental uraemia: evidence for a permissive action of PTH.

BACKGROUND: Abnormalities in cardiovascular structures, e.g. LV hypertrophy and thickening of vessels (arteries, arterioles, veins) are hallmarks of renal failure. They are in part independent of elevated blood pressure. Parathyroid hormone (PTH) has been shown to affect cardiac function and has also been identified as a permissive factor in the genesis of cardiac fibrosis. PURPOSE OF THE STUDY: The present study in rats with experimental renal failure was designed to examine whether PTH was permissive for wall thickening of intramyocardial arterioles as well. METHODS: Male SD rats were sham operated or subtotally nephrectomized and maintained for 2 weeks. Subgroups of subtotally nephrectomized (SNX) rats were parathyroidectomized (PTX). Saline or rat 1, 34 PTH was administered by osmotic minipump. Eucalcaemia was maintained in PTX animals by a high-calcium diet (3%). Serum calcium was not statistically different between the groups. After perfusion fixation, intramyocardial arterioles were assessed using stereological techniques (wall thickness; wall/lumen ratio; minimal lumen diameter; length density). RESULTS: In random samples of the left ventricle, wall thickness of arterioles was 2.2 +/- 0.25 microns in sham-op controls and 2.76 +/- 0.41 in SNX (n = at least 8 animals per group). SNX-PTX animals+solvent did not differ significantly from sham-op controls (2.08 +/- 0.42 microns), while SNX-PTX animals+PTH had values not significantly different from SNX (2.59 +/- 0.54 microns). Differences in wall thickness were not paralleled by differences in systolic blood pressure (sham-op 110 +/- 13.3 mmHg; SNX 138 +/- 8.4 mmHg, SNX-PTX+solvent 142 +/- 5.2 mmHg; SNX-PTX+PTH 148 +/- 5.7 mmHg). PTH treated animals showed signs of marked vascular smooth-muscle cell and endothelial-cell activation. CONCLUSIONS: The data suggest that wall thickening of intramyocardial arterioles in short-term experimental uraemia is dependent upon the presence of PTH (permissive effect).

Animals↗
PubMed1994

A role of parathyroid hormone for the activation of cardiac fibroblasts in uremia.

Intermyocardiocytic fibrosis, i.e., nonreparative interstitial fibrosis with collagen fiber deposition, is commonly found in uremic patients and animals. The volume density of interstitial tissue in the left papillary muscle of uremic animals was found to be increased (from 1.9 +/- 0.7 to 4.2 +/- 1.1%; P < 0.001). The nuclei of interstitial cells, but not of endothelial cells, were enlarged, pointing to an activating signal that specifically acts on interstitial cells. Because of the known action of parathyroid hormone (PTH) on the heart, a potential role of PTH in the genesis of fibrosis was explored by comparing subtotally nephrectomized (NX) parathyroidectomized (PTX) rats receiving by osmotic minipump either saline or rat 1,34 PTH (100 ng/kg per hour dissolved in NaCl). Animals were on a standard 0.95% Ca diet. After PTX, they were switched to a high-calcium (3%) diet. At the end of the 14-day experiments, NX-PTX-PTH animals and NX-PTX-solvent animals were comparable with respect to mean body weight (335 versus 338 g), serum creatinine (1.2 versus 1.2 mg/dL), and serum-Ca (2.66 versus 2.63 mmol/L). The volume densities of cardiac interstitium were 4.71 +/- 0.87 versus 1.49 +/- 0.49, and those of capillaries were 8.07 +/- 1.54 versus 7.94 +/- 2.62, respectively (P < 0.001 by analysis of variance). Thus, PTX abolished and PTH restored intermyocardiocytic changes of experimental uremia. These observations argue for a permissive role of PTH for fibroblast activation and the genesis of the cardiac fibrosis of uremia.

Animals↗