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T Sladek

Publications and source records attributed to T Sladek.

3 recordsLinked to original sources
PubMed1996

The effect of AT1 receptor antagonist on chronic cardiac response to coronary artery ligation in rats.

OBJECTIVE: The aim was to study the effect of the AT1 receptor antagonist losartan on hemodynamic and morphometric changes following experimental infarction. METHODS: Experimental infarction was produced in adult male rats by ligating the coronary artery. Treatment with losartan was compared to untreated controls, in rats with experimental infarction and sham-operated animals. RESULTS: Infarcted hearts were characterized by significant decreases in left ventricular developed pressure, as well as positive and negative (dP/dt)max, whereas left ventricular end-diastolic pressure (LVEDP), relaxation constant tau and right ventricular systolic pressure (RVSP) significantly increased. Treatment with losartan decreased the LVEDP, the relaxation constant tau and RVSP in the infarcted hearts. Right ventricular weight significantly increased in rats with infarction; this was attenuated by losartan. Infarct size was not significantly influenced by losartan treatment. Morphometric data revealed decreased capillary supply in infarcted hearts, especially in regions close to infarction; the decrease was less pronounced after losartan treatment. Capillary density in near infarct region decreased from 2826/mm2 to 1471/mm2 in untreated animals but in the treated animals it decreased from 2982/mm2 to only 2037/mm2. Simultaneous significant decrease in myocyte-to-capillary ratio in treated animals compared to untreated rats (0.87 to 0.67) seems to indicate formation of new capillary channels after losartan treatment. LVEDP was dependent on the size of infarction in untreated but not in treated animals. A close correlation between LVEDP and capillary density was found. CONCLUSIONS: Decreased ventricular contractility, prolonged relaxation and decreased coronary capillary density in rat experimental cardiac infarction confirm and amplify previous reports dealing with this experimental model. Moreover, we have found evidence of improved hemodynamics and coronary angiogenesis after losartan treatment.

Angiotensin I↗
PubMed1993

G protein beta gamma subunit: physical and chemical characterization.

The beta gamma subunits of heterotrimeric G proteins play a central role in regulating the function of the G protein alpha subunits and in modulating the activity of several enzymes and ion channels. We have used the signature tryptic cleavage pattern of native beta gamma from bovine brain as a starting point for our analysis of its physical and chemical properties. Digestion of bovine brain beta gamma with trypsin yields only 2 beta-derived fragments, with relative mobilities on SDS-PAGE of 14 kDa (amino terminal) and 27 kDa (carboxyl terminal), despite the presence of 32 potential tryptic cleavage sites in the beta 1 subunit. Trypsin-cleaved beta gamma remains in a complex that has the same apparent sedimentation coefficient as intact beta gamma, and retains its ability to associate functionally with the alpha o subunit. Comparison of the incorporation of [14C]iodoacetamide into reduced denatured beta and unreduced denatured beta showed that there are no disulfide bonds in the molecule to hold the complex together. The brain beta and gamma subunits can be cross-linked by 1,6-bis(maleimido)hexane to form a 46-kDa product on SDS-PAGE, and trypsin cleavage of cross-linked beta gamma shows that gamma is cross-linked to the 14-kDa amino-terminal fragment of the beta subunit. On the basis of its primary sequence, the beta subunit is predicted to form a repetitive structure encompassing the 27-kDa fragment and part of the 14-kDa fragment. Analysis of the thermal denaturation of trypsin-cleaved beta gamma supports this prediction and confirms that both fragments retain stable tertiary structures following tryptic cleavage.(ABSTRACT TRUNCATED AT 250 WORDS)

Carbon Radioisotopes↗