H. Suzuki et al., MODIFICATION OF LEUKOCYTE ADHESION IN SPONTANEOUSLY HYPERTENSIVE RATSBY ADRENAL CORTICOSTEROIDS, Journal of leukocyte biology, 57(1), 1995, pp. 20-26
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.