An in-vivo analysis of capillary stasis and endothelial apoptosis in a model of hypertension.
OBJECTIVE
Recent evidence suggests endothelial apoptosis may be a mechanism for capillary rarefaction in hypertensives. The objective of this study was to examine the early phase of endothelial apoptosis and capillary blood flow in the spontaneously hypertensive rat (SHR) and the normotensive Wistar-Kyoto (WKY) rat.


METHODS
Since hypertension in SHR is dependent on glucocorticoids, the animals were treated with dexamethasone (DEX), by intraperitoneal injection and then by superfusion on exposed mesentery. Selected capillaries were continuously observed. Annexin V and propidium iodide were used to detect apoptosis.


RESULTS
Without central pressure reduction, permanent capillary stasis was initiated by the entrapment of leukocytes at the location of an endothelial cell that had platelets attached to it. Apoptosis of the endothelial cell was followed by apoptosis in other endothelial cells of the obstructed capillary. The incidence of stasis and total cell death in WKY+DEX were higher than WKY, whereas there were no differences between SHR+DEX and SHR. Blockade of the lectin do main of L-selectin or a platelet membrane adhesion molecule (glycoprotein IIb/IIIa) blocked the development of stasis.


CONCLUSIONS
Glucocorticoid facilitates cell death and microvessel stasis. Immobilized platelets and leukocytes play a central role in capillary stasis, which leads to progression of endothelial apoptosis.
Tran
Edward D
ED
Department of Bioengineering, the Whitaker Institute for Biomedical Engineering Ulniversity of California San Diego, La Jolla 92093-0412, USA. etran@ucsd.edu
Schmid-Schönbein
Geert W
GW
D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001783:Blood Flow Velocity / Q000187:drug effects; D002196:Capillaries / Q000378:metabolism / Q000473:pathology; D003907:Dexamethasone / Q000494:pharmacology*; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D006973:Hypertension / Q000378:metabolism* / Q000473:pathology; D019041:L-Selectin / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism / Q000473:pathology; D008297:Male; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D017304:Annexin A5; D000893:Anti-Inflammatory Agents; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D019041:L-Selectin; D003907:Dexamethasone