Impaired leukocyte-endothelial cell interaction in spontaneously hypertensive rats.
Hypertension is associated with a progressive organ injury whose etiology remains largely speculative. An increasing database shows that activated leukocytes, while affording an important immune protection, may be a contributing factor to several of the pathogenetic features of the hypertension syndrome. The purpose of this study was to determine the extent to which the glucocorticoid pathway may be involved in the atypical kinetics of leukocytes in spontaneously hypertensive rats (SHR) compared with normotensive Wistar-Kyoto (WKY) rats. The typical venular leukocyte adhesion induced by histamine application was significantly lower in SHR, and a comparison of normalized leukocyte rolling velocity (VWBC/VRBC) showed the values to be significantly higher in SHR relative to WKY controls. This abnormal trend in adherent leukocyte numbers and in VWBC/VRBC values could be counteracted when SHR were pretreated with RU 486, a synthetic glucocorticoid inhibitor, and restored to the levels observed in WKY rats. Anti-P-selectin monoclonal antibody (PB1.3) attenuated in SHR and WKY rats the increment of adherent leukocyte numbers as well as the decrement of VWBC/VRBC value that developed under combined histamine and RU 486 superfusion. Furthermore, an anti-intercellular adhesion molecule-1 monoclonal antibody (1A29) served to attenuate the increment of adherent leukocyte number induced by a combination of histamine and RU 486 superfusion in WKY rats and SHR. The results indicate that the deficient leukocyte-endothelial cell interaction in SHR can be circumvented by a glucocorticoid inhibitor.
Suzuki
H
H
Institute for Biomedical Engineering, University of California, San Diego, La Jolla 92093-0412.
Schmid-Schönbein
G W
GW
Suematsu
M
M
DeLano
F A
FA
Forrest
M J
MJ
Miyasaka
M
M
Zweifach
B W
BW
D000818:Animals; D002450:Cell Communication; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D006854:Hydrocortisone / Q000494:pharmacology; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology*; D015735:Mifepristone / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013314:Stress, Mechanical; D014699:Venules / Q000502:physiology
D015735:Mifepristone; D006854:Hydrocortisone