Relationship between changes in response to mechanoreceptor stimulation of endocardial endothelial cells and the development of heart failure

We estimated the effects of mechanical stress such as shear stress and transmural pressure on the production of vasoactive substances from endocardial endothelial cells(EECs)isolated from porcine hearts and from young(5-week-old)and aged(100-week-old)rat hearts。We also demonstrated age-related changes in rat cardiac functions，with the Langendorff and Working heart apparatus.Results and Conclusion1：Shear stress(0.2~6dyne/cm I D12文件D1)and transmural pressure(0~150 mmHg)increased prostacycline(PGI I D22文件D2)production from porcine EECs.Shear stress-induced PGI I D22 ii D2 production was significantly inhibited from cells exposed to8-(Dimetylamino)octyl 3，4，5-trimethoxybenzoate hydrochloride(An Inhibitor Of Intracellular Calcium Mobilization)or cyclopiazonic acid(and endoplasmic reticulum Ca I D12+I D1-ATPase inhibitor)；Moreover，the production decreased from EECs of aged rats rather than from those of young rats.2：Proliferation of rat EECs decreased with aging，in association with the morphological enlargement of the cells.3：Phase-contrast electron microscopy revealed the enlargement of right ventricular EECs isolated from rat hearts with right vicular hypertrophy induced by subcutaneous injection of right ventricular of the cells.In rats mechanotransduction decreased with aging，and，morphologically，the right ventricular EECs enlarged with advancing age and with right ventricular hypertrophy.These results suggest that endocardial dysfunction participates in the development of heart failure.

We estimated the effects of mechanical stress such as shear stress and transmural pressure on the production of vasoactive substances from endocardial endothelial cells (EECs) isolated from porcine hearts and from young (5-week-old) and aged (100-week-old) rat hearts. We also demonstrated age-related changes in rat cardiac functions, with the Langendorff and Working heart apparatus.Results and Conclusion1 : Shear stress (0.2〜6dyne/cmィイD12ィエD1) and transmural pressure (0〜150mmHg) increased prostacycline (PGIィイD22ィエD2) production from porcine EECs. Shear stress-induced PGIィイD22ィエD2 production was significantly inhibited from cells exposed to 8-(dimetylamino) octyl 3, 4, 5-trimethoxybenzoate hydrochloride (an inhibitor of intracellular calcium mobilization) or cyclopiazonic acid ( and endoplasmic reticulum CaィイD12+ィエD1-ATPase inhibitor) ; moreover, the production decreased from EECs of aged rats rather than from those of young rats.2 : Proliferation of rat EECs decreased with aging, in association with the morphological enlargement of the cells.3 : Phase-contrast electron microscopy revealed the enlargement of right ventricular EECs isolated from rat hearts with right ventricular hypertrophy induced by subcutaneous injection of monocrotaline.4 : Cardiac output, aortic flow and heart rates of rats decreased significantly with advancing age.Shear stress enhances PGIィイD22ィエD2 production from EECs, and the mechanotransduction of shear stress depends on calcium mobilization in EECs. in rats mechanotransduction decreased with aging, and, morphologically, the right ventricular EECs enlarged with advancing age and with right ventricular hypertrophy. These results suggest that endocardial dysfunction participates in the development of heart failure.