MODIFICATION OF LEUKOCYTE ADHESION IN SPONTANEOUSLY HYPERTENSIVE RATSBY ADRENAL CORTICOSTEROIDS

Leukocyte adhesion is a key factor in the pathogenesis of organ injury following a variety of stimuli. In this study we have addressed the r ole of leukocyte adhesion in hypertensives as a risk factor for organ injury. In the spontaneously hypertensive rat(SHR), the number of circ ulating leukocytes and their level of activation are significantly inc reased compared with its normotensive control, the Wistar-Kyoto rat (W KY). We have demonstrated that elevated levels of glucocorticoid in SH R suppress P-selectin-mediated leukocyte-endothelial interaction in th e microcirculation. It is possible that the disturbance in leukocyte-e ndothelial interactions may result in an elevated number of leukocytes in the circulation. The aim of the present study was to investigate t he contribution of the adrenal glands to the disturbance in leukocyte behavior in SHR by subjecting the animals to bilateral adrenalectomy a nd investigating the effect of hydrocortisone. In addition, we have st udied by immunohistochemistry the expression of the endothelial adhesi on molecule, P-selectin, in response to histamine in the mesenteric ve nules of normal and adrenalectomized SHR and WKY. The elevated blood p ressure, above-normal leukocyte counts, and elevated number of activat ed neutrophils (nitroblue tetrazolium test) in SHR were blunted after adrenalectomy. The blunted histamine-induced leukocyte-endothelial int eraction in the mesenteric venules of SHR was restored after adrenalec tomy. Treatment with hydrocortisone significantly attenuated the eleva ted leukocyte adhesion in the adrenalectomized SHR as well as in WKY. The suppressed P-selectin expression in SHR mesentery was restored aft er adrenalectomy. In conclusion, the subnormal leukocyte-endothelial i nteraction in response to an inflammatory stimulation in SHR 6 abolish ed after adrenalectomy, suggesting a relationship between the altered leukocyte adhesiveness and the adrenal corticosteroids in hypertensive s.