Biomedical subjects

C Kolbeck-Rühmkorff

Publications and source records attributed to C Kolbeck-Rühmkorff.

4 recordsLinked to original sources

PubMed1997

Correlation between function and proto-oncogene expression in isolated working rat hearts under various overload conditions.

In isolated perfused working rat hearts we have studied the effects of norepinephrine (NE) and of pressure as well as volume overload alone, and in combination on heart function and expression of the proto-oncogenes c-fos and c-myc. This preparation was functionally stable over the observation period of 120 min. NE (3x10(-8) M) induced an immediate and sustained increase in aortic and coronary flow as well as in cardiac output. Volume overload was established by increasing left atrial filling pressure (preload) from 8-16 cm H2O and resulted in a marked increase in aortic flow and cardiac output which subsided somewhat over time. Pressure overload was created by elevation of afterload from 80-100 cm H2O and induced a decrease in aortic flow and a slight increase in coronary flow. Using specific cDNA clones, the mRNAs of c-fos and c-myc were measured by Northern blots and quantified with densitometry. In all three conditions, c-fos mRNA was increased first, after 30 min. It was more pronounced and of longer duration in the NE-stimulated hearts. The increase in c-myc-mRNA occurred after 60 or 90 min. After 120 min, all signals were normal, although heart function was still altered in a manner specific for the respective intervention. Combination of NE with preload and afterload elevation as well as combination of preload and afterload elevation led first to an increase in cardiac output which was followed by a decline to various degrees. In all these combinations, the c-fos mRNA signal appeared earlier, after 15 min, and persisted for a longer period of time compared with the effect of a single stimulus. The c-myc mRNA was increased later, after 30 or 60 min. This increase persisted throughout the entire observation period, showing a further progressive rise. These results show that stimuli which cause cardiac hypertrophy in vivo induce a transient and sequential increase in proto-oncogene expression in the isolated working rat heart. Combination of two hypertrophy-inducing stimuli elicit an earlier, more pronounced and longer-lasting expression of the proto-oncogenes c-fos and c-myc, while functional parameters deteriorate.

Analysis of Variance↗

PubMed1995

Proto-oncogene expression in the isolated working rat heart: combination of pressure and volume overload with norepinephrine.

We have studied the effects of pressure and volume overload as well as of norepinephrine (NE) alone and in combination on the expression of the proto-oncogenes c-fos and c-myc in isolated perfused working rat hearts. Using specific cDNA clones, the mRNAs of c-fos and c-myc were measured by Northern blots and quantified with densitometry. Total RNA was isolated from hearts after stimulation with NE (3 x 10(-8) M), after increasing left atrial filling pressure (preload) from 8 to 16 cmH2O, and after elevation of afterload from 80 to 100 cmH2O for 15, 30, 60, 90, and 120 min. NE increased the expression of c-fos and c-myc after 30 and 60 min, respectively. This enhancement occurred at about the same time as that induced by elevation of pre- and afterload, but was more pronounced. Combination of NE with pre- and afterload elevation induced the c-fos mRNA signal to appear earlier and to persist for a longer period of time. Similar results were obtained in regard to the c-myc mRNA, however, the signal was more pronounced in intensity. Simultaneous pre- and afterload increase also led to an earlier expression of the proto-oncogenes and to a longer duration of the signals. These results indicate that the combination of two hypertrophy-inducing stimuli, which may cause a higher degree of cardiac hypertrophy in vivo, induce an earlier, more pronounced and longer-lasting expression of the protooncogenes c-fos and c-myc.

Animals↗

PubMed1993

Effect of pressure and volume overload on proto-oncogene expression in the isolated working rat heart.

OBJECTIVE: The aim was to study the effect of pressure and volume overload on the expression of the proto-oncogenes, c-fos and c-myc, in isolated perfused working rat hearts and to compare these results with the known effects of noradrenaline. METHODS: Working rat hearts were obtained by converting the Langendorff preparation into the working mode by perfusion through the left atrium. Using specific cDNA clones, the mRNAs of c-fos and c-myc were measured by northern blots and quantified with densitometry. Total RNA was isolated from hearts after stimulation with noradrenaline (3 x 10(-8) M), after increasing afterload from 80 to 100 cm H2O, and left atrial filling pressure (preload) from 8 to 16 cm H2O for 15, 30, 60, 90, and 120 min, respectively. RESULTS: The mRNAs of c-fos and c-myc were not detectable in freshly excised rat hearts. When the hearts were perfused in the working mode for 15, 30, 60, 90, and 120 min, c-fos and c-myc mRNAs were measurable, and these mRNA levels served as control baseline values that were set at 100%. When noradrenaline was infused, c-fos mRNA was increased fivefold after 30, threefold after 60, and 3.8-fold after 90 min. The mRNA of c-myc was increased 1.8-fold after 60 min and 3.8-fold after 90 min. The increase in afterload induced a threefold increase of c-fos mRNA after 30 min and a threefold increase of c-myc mRNA after 90 min. When preload was increased, c-fos mRNA rose 1.8-fold after 30 min, and c-myc mRNA twofold after 60 min and 2.8-fold after 90 min compared to the controls. CONCLUSIONS: Pressure and volume overload have effects on the expression of c-fos and c-myc mRNA that are similar to those obtained with noradrenaline stimulation which induced the most pronounced signals. Our time course studies showed that c-fos mRNA always rose before c-myc mRNA. This common sequential induction pattern may have important signal function in the processes that trigger the development of cardiac hypertrophy.

Animals↗

PubMed1992

Effects of norepinephrine on the oxidative pentose phosphate pathway in the rat heart.

To examine whether stimulation of alpha-adrenergic receptors may affect the oxidative pentose phosphate pathway (PPP) in the rat heart, norepinephrine (NE) and the alpha-adrenergic agonist norfenephrine were used. NE was administered as a continuous intravenous infusion in awake rats for 3 days. It stimulated the activity of cardiac glucose-6-phosphate dehydrogenase (G-6-PD), the first and regulating enzyme of the oxidative PPP, in a dose-dependent manner. With the highest dose (0.2 mg.kg-1.hr-1), there was also a time-dependent enhancement. The increase observed after 48 hours was attenuated partially by the beta-receptor blocker metoprolol and the alpha-receptor blocker prazosin. It was entirely abolished when both drugs were administered. Carvedilol, a beta-adrenergic blocker and vasodilator with alpha 1-blocking activity (0.5 mg.kg-1.hr-1), prevented the NE-induced increase in cardiac G-6-PD activity, in functional parameters (heart rate, left ventricular systolic pressure, and left ventricular dP/dtmax), and in the heart weight/body weight ratio. The alpha-adrenergic stimulator norfenephrine increased myocardial G-6-PD activity; prazosin prevented this stimulation. NE and norfenephrine also elevated the available pool of cardiac 5-phosphoribosyl-1-pyrophosphate. G-6-PD activity was enhanced in cardiac myocytes freshly isolated from the left ventricle of rats that had received NE infusion for 3 days (12.3 +/- 1.4 units/g protein) compared with control rats (1.5 +/- 0.4 units/g protein). The activity of 6-phosphogluconate dehydrogenase, one of the enzymes in the oxidative PPP, was elevated only moderately from 12.7 +/- 0.7 to 19.1 +/- 1.4 units/g protein. Combined alpha- and beta-receptor blockade with carvedilol attenuated these effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗