IMPAIRED LEUKOCYTE-ENDOTHELIAL CELL-INTERACTION IN SPONTANEOUSLY HYPERTENSIVE RATS

Hypertension is associated with a progressive organ injury whose etiol ogy remains largely speculative. An increasing database shows that act ivated leukocytes, while affording an important immune protection, may be a contributing factor to several of the pathogenetic features of t he hypertension syndrome. The purpose of this study was to determine t he extent to which the glucocorticoid pathway may be involved in the a typical kinetics of leukocytes in spontaneously hypertensive rats (SHR ) compared with normotensive Wistar-Kyoto (WKY) rats. The typical venu lar leukocyte adhesion induced by histamine application was significan tly lower in SHR, and a comparison of normalized leukocyte rolling vel ocity (V-WBC/V-RBC) showed the values to be significantly higher in SH R relative to WKY controls. This abnormal trend in adherent leukocyte numbers and in V-WBC/V-RBC values could be counteracted when SHR were pretreated with RU 486, a synthetic glucocorticoid inhibitor, and rest ored to the levels observed in WKY rats. Anti-P-selectin monoclonal an tibody (PB1.3) attenuated in SHR and WKY rats the increment of adheren t leukocyte numbers as well as the decrement of V-WBC/ V-RBC value tha t developed under combined histamine and RU 486 superfusion. Furthermo re, an anti-intercellular adhesion molecule-1 monoclonal antibody (1A2 9) served to attenuate the increment of adherent leukocyte number indu ced by a combination of histamine and RU 486 superfusion in WKY rats a nd SHR. The results indicate that the deficient leukocyte-endothelial cell interaction in SHR can be circumvented by a glucocorticoid inhibi tor.