Decrease in heart adrenoceptor gene expression and receptor number as compensatory tool for preserved heart function and biological rhythm in M(2) KO animals
Jazyk angličtina Země Německo Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
- MeSH
- atropin farmakologie MeSH
- beta-1-adrenergní receptory metabolismus MeSH
- beta-2-adrenergní receptory metabolismus MeSH
- bradykardie patofyziologie MeSH
- funkce levé komory srdeční fyziologie MeSH
- isoprenalin farmakologie MeSH
- karbachol farmakologie MeSH
- myši knockoutované MeSH
- myši MeSH
- propranolol farmakologie MeSH
- receptor muskarinový M2 genetika MeSH
- regulace genové exprese * MeSH
- srdeční frekvence fyziologie MeSH
- srdeční komory metabolismus MeSH
- vazba proteinů MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- atropin MeSH
- beta-1-adrenergní receptory MeSH
- beta-2-adrenergní receptory MeSH
- isoprenalin MeSH
- karbachol MeSH
- propranolol MeSH
- receptor muskarinový M2 MeSH
Muscarinic receptors (MR) are main cardioinhibitory receptors. We investigated the changes in gene expression, receptor number, echocardiography, muscarinic/adrenergic agonist/antagonist changes in heart rate (HR) and HR biorhythm in M(2) KO mice (mice lacking the main cardioinhibitory receptors) in the left ventricle (LV) and right ventricle (RV). We hypothesize that the disruption of M(2) MR, key players in parasympathetic bradycardia, would change the number of receptors with antagonistic effects on the heart (β(1)- and β(2)-adrenoceptors, BAR), while the function of the heart would be changed only marginally. We have found changes in LV, but not in RV: decrease in M(3) MR, β(1)- and β(2)-adrenoceptor gene expressions that were accompanied by a decrease in MR and BAR receptor binding. No changes were found both in LV systolic and diastolic function as assessed by echocardiography (e.g., similar LV end-systolic and end-diastolic diameter, fractional shortening, mitral flow characteristics, and maximal velocity in LV outflow tract). We have found only marginal changes in specific HR biorhythm parameters. The effects of isoprenaline and propranolol on HR were similar in WT and KO (but with lesser extent). Atropine was not able to increase HR in KO animals. Carbachol decreased the HR in WT but increased HR in KO, suggesting the presence of cardiostimulatory MR. Therefore, we can conclude that although the main cardioinhibitory receptors are not present in the heart, the function is not much affected. As possible mechanisms of almost normal cardiac function, the decreases of both β(1)- and β(2)-adrenoceptor gene expression and receptor binding should be considered.
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