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Presence of transendothelial channels in cerebral endothelium in chronic hypertension
1Department of Pathology (Neuropathology), Queen's University, Kingston, Ontario, Canada.
Insights
Hypertension rapidly reduces calcium pump activity in cerebral vessels, leading to increased permeability. This facilitates plasma protein leakage into the brain, contributing to conditions like cerebral edema.
Area of Science:
- Cardiovascular Science
- Neuroscience
- Cell Biology
Background:
- Hypertension is linked to vascular abnormalities.
- Cerebral vessel permeability is altered in chronic hypertension.
- Ionic calcium plays a role in vascular function.
Purpose of the Study:
- To investigate early changes in cerebral vessels during hypertension.
- To determine the role of Ca2(+)-ATPase in hypertension-induced permeability.
- To elucidate the mechanism of plasma protein transport into the brain.
Main Methods:
- Surgical induction of hypertension in a rat model.
- Measurement of Ca2(+)-ATPase activity in cerebral vessels.
- Assessment of endothelial permeability to plasma proteins.
- Localization of Ca2(+)-ATPase in endothelial vesicles.
Main Results:
- Hypertension developed within 1 week post-surgery.
- Ca2(+)-ATPase activity was reduced in cerebral vessels.
- Cerebral cortical arterioles showed increased permeability to plasma proteins.
- Enhanced pinocytosis was identified as the primary mechanism for increased permeability.
- Ca2(+)-ATPase was localized in endothelial pinocytotic vesicles, suggesting a role in transendothelial transport.
Conclusions:
- Early hypertension involves reduced Ca2(+)-ATPase activity in cerebral vessels.
- Increased endothelial permeability and plasma protein transport into the brain occur via enhanced pinocytosis.
- Transendothelial channels formed by fused vesicles may facilitate protein transport in pathological states like cerebral edema.
Abstract:
In this model hypertension developed as early as 1 wk. post-surgery and was associated with reduction in Ca2(+)-ATPase activity in cerebral vessels indicating that abnormalities in ionic calcium in vessel walls occur early in the evolution of hypertension. This study supports previous observations that cerebral cortical arterioles develop increased permeability to endogenous plasma proteins in chronic hypertension. The principal mechanism resulting in this increased permeability is enhanced pinocytosis. Ca2(+)-ATPase localisation in endothelial pinocytotic vesicles helped to localise transendothelial channels in occasional vessels of hypertensive rats. The latter findings reinforce the concept that in pathologic states associated with cerebral oedema, pinocytotic vesicles fuse to form transendothelial channels which transport plasma proteins into brain.