PERITONEAL LEUKOCYTES FROM SPONTANEOUSLY HYPERTENSIVE RATS HAVE REDUCED CHEMILUMINESCENCE RESPONSE AND LOWERED SENSITIVITY TO DEXAMETHASONEIN-VIVO

The genetically altered hypothalamo-pituitary-adrenocortical axis in t he spontaneously hypertensive rat (SHR) suggests altered phagocyte fun ction in this strain. We therefore compared luminol-amplified chemilum inescence in peritoneal leucocytes from 10- to 12-week-old SHRs and ag e-matched Wistar-Kyoto rats (WKYs) activated by serum-opsonized zymosa n particles (SOZ). N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP ) or phorbol 12-myristate 13-acetate (PMA). While the number of perito neal monocytes/macrophages was increased by 49% in SHRs relative to WK Ys, activator-induced chemiluminescence per cell in SHRs was only 14-4 2% of that in WKYs. FMLP responses were especially low in SHRs. Treatm ent of rats with dexamethasone in the drinking water for 48 h prior to ex vivo experiments reduced chemiluminescence dose-dependently in WKY s as well as in SHRs. ED,, of dexamethasone in SHRs was. however, incr eased compared to WKYs. indicating lowered sensitivity to dexamethason e in SHRs. No evidence was found of strain differences in differential distribution of peritoneal cells or in pharmacokinetics of dexamethas one. Plasma ACTH levels were significantly higher in SHRs than in WKYs , while basal plasma corticosterone concentrations in SHRs and WKYs we re not significantly different. The results suggest that production of reactive oxygen compounds by peritoneal mononuclear phagocytes is red uced in SHRs compared with WKYs, and that the phagocyte respiratory bu rst is modulated differently by endogenous glucocorticoids in the two strains. We propose that reduced activity of the phagocyte NADPH oxida se-myeloperoxidase system is a major contributory cause of the altered chemiluminescence responses in SH Rs. The data indicate that species differences may also be present at earlier steps in the signal transdu ction pathways activated by SOZ, fMLP and PMA.