Involvement of nitric oxide in the blastogenic response deficiency in splenocytes from spontaneously hypertensive rats.

It has been shown that spontaneously hypertensive rats (SHR) exhibit some abnormalities in their immune system. These include a reduced delayed hypersensitivity response, a reduction in the number of rosette-forming cells and a decreased lymphocyte blastogenic response. In this study, we further investigated the blastogenic responses of splenocytes, thymocytes, and T-enriched lymphocytes from SHR. In SHR splenocytes, the blastogenic responses to concanavalin A (Con A), phytohemagglutinin (PHA), interleukin-2 (IL-2), and phorbol 12,13-dibutyrate (PDB) plus ionomycin were significantly reduced compared with those from Wistar-Kyoto rats (WKY). In SHR thymocytes and T-enriched lymphocytes, the blastogenic responses to these activators were the same as in WKY rats. The IL-2 production by SHR splenocytes was similar to that of WKY. To elucidate the possible mechanism responsible for the blastogenic defects in SHR splenocytes, the involvement of the nitric oxide (NO) synthetic pathway was studied. The inhibition of NO synthesis by NG-monomethyl-L-arginine (L-NMMA) corrected the defect in SHR splenocytes. L-NMMA had no effect on the splenocytes, thymocytes, or macrophage-depleted splenocytes from WKY or on thymocytes or macrophage-depleted splenocytes from SHR. The removal of macrophages from SHR splenocytes also corrected the blastogenic defect in these cells. Furthermore, the NO synthesis in Con A stimulated SHR splenocyte culture medium was statistically significantly higher than that in WKY. These results suggested that overproduction of nitric oxide by SHR macrophages may be responsible for the SHR splenocyte blastogenic defect.