Cellular and receptor mechanisms of impairment of myocardium and aorta contractilityat Alzheimers disease model

Abstract

Introduction. Recent studies certify the existence of linkbetween Alzheimers disease and cardiovascular pathology,however the mechanisms of this phenomenon is unclear. Herewe studied the influence of Alzheimers β-amyloid peptide(βAP) on the contractility of rat myocardium and aorta.Material and methods. Contractility of myocardium ventriclestrips and transverse fragments of abdominal aorta wasmeasured at Power Lab setup using conventional myographictechnique. Contractile responses of aorta strips were evokedby application of receptor agonists, contractile responses ofmyocardium - by electrical stimulation. Contractile responsesof aorta strips after application of carbachol (10-6-10-4 М),histamine (10-6-10-4 М), norepinephrine (10-5-10-3 М) andATP (10-6-10-4 М) were measured.Results and discussion. We found the impairment ofcarbachol- and histamine-induced contractility of aorta,appearing as perverse contractile reactions (relaxation insteadof contraction) under the action of βAP (10-6 М). Next, wefound βAP-induced impairments of ventricle myocardiumcontractility, appearing as decrease of relaxation phaseduration and increase of relaxation speed (positive lusitropiceffect). Also, own positive lusitropic effect of norepinephrinewas absent in presence of βAP (10-6М).Thus, βAP(25-35) significantly impairs the contractilityof rat myocardium and aorta, as well as processes of itsregulation. Obtained data significantly broad our understandingof mechanisms of Alzheimers disease pathogenesis andpathophysiology of cardiovascular system.

Keywords

β-amyloid peptide / Alzheimer's disease / myocardium / aorta / contractility / lusitropic effect

References

[1] de Toledo Ferraz Alves T.C., Ferreira L.K., Wajngarten M. et al. Cardiac disorders as risk factors for Alzheimer's disease. J. Alzheimers. Dis. 2010; 20: 749-63.

[2] Dolan H., Crain B., Troncoso J. et al. Atherosclerosis, dementia, and Alzheimer disease in the Baltimore. Longitudinal study of aging cohort. Ann. Neurol. 2010; 68: 231-40.

[3] Skoog I., Lernfelt B., Landahl S. et al. 15-year longitudinal study of blood pressure and dementia. Lancet 1996; 347: 1141-5.

[4] Love S., Miners S., Palmer J. et al. Insights into the pathogenesis and pathogenicity of cerebral amyloid angiopathy. Frontiers in Bioscience 2009; 14: 4778-92.

[5] Walsh D.M., Selkoe D.J. A beta oligomers - a decade of discovery. J. Neurochem. 2007; 101: 1172-84.

RIGHTS & PERMISSIONS

Eco-Vector