Microvascular endothelial cell death and rarefaction in the glucocorticoid-induced hypertensive rat.
OBJECTIVE
The objective was to quantify and to describe microvascular endothelial cell death in glucocorticoid-induced hypertension. Microvascular rarefaction, which has been shown in human and animal hypertension, may result from increased endothelial cell apoptosis.


METHODS
Wistar rats were administered the synthetic glucocorticoid dexamethasone (0.5 mg/kg b.w. per day, i.m.) for 5 days and were compared with a group of control rats treated with the vehicle. In vivo microvascular endothelial cell death was quantified by propidium iodide fluorescent labeling in the mesentery. Normal nuclear DNA (labeled with Hoechst 33342) and DNA with apoptotic characteristics in muscle endothelium (labeled with ethidium bromide) were visualized using confocal imaging. Microvessel length density was measured by using a fluorescein isothyocyanate-labeled lectin technique.


RESULTS
The dexamethasone-treated rats exhibit approximately a 10% increase in cell death along the mesenteric arteriolar and venular endothelium compared with controls. Confocal analysis of cremaster muscle in dexamethasone-treated rats demonstrated nuclear fragmentation and decreased nuclear volumes in dying endothelial cells, which are consistent with an apoptotic process. The capillary length density in cremaster muscle was decreased on average by 16% in the hypertensive rats.


CONCLUSIONS
These results suggest capillary structural rarefaction by an increased rate of apoptotic endothelial cell death in glucocorticoid-induced hypertension.
Vogt
C J
CJ
Department of Bioengineering, Whitaker Institute for Biomedical Engineering, University of California, San Diego, La Jolla 92093-0412, USA. gwss@bioeng.ucsd.edu
Schmid-Schönbein
G W
GW
D000818:Animals; D017209:Apoptosis; D001794:Blood Pressure; D002196:Capillaries / Q000473:pathology; D003907:Dexamethasone / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000473:pathology*; D006973:Hypertension / Q000473:pathology*; D018482:Muscle, Skeletal / Q000098:blood supply; D051381:Rats; D017208:Rats, Wistar
D003907:Dexamethasone