Nitric oxide mediates immune dysfunction in the spontaneously hypertensive rat

Area of Science:

• Immunology
• Hypertension Research
• Macrophage Biology

Background:

• Spontaneously hypertensive rats exhibit immune system dysfunction.
• Previous studies identified macrophages as mediators of this immunodepression.
• The specific mechanism of depressed splenic mononuclear cell proliferation in SHR requires elucidation.

Purpose of the Study:

• To investigate the mechanism behind the suppressed concanavalin A-induced proliferation of splenic mononuclear cells in spontaneously hypertensive rats.
• To identify macrophage-derived products responsible for inhibiting lymphoid function in this model.

Main Methods:

• Testing various inhibitors of known macrophage suppressive products, including NG-monomethyl L-arginine (a nitric oxide synthetase inhibitor), indomethacin, and catalase.
• Measuring nitric oxide (NO) production by splenic mononuclear cells from spontaneously hypertensive rats and Wistar-Kyoto rats.
• Assessing the effect of L-arginine and antibodies to interferon gamma on cell proliferation and NO levels.

Main Results:

• NG-monomethyl L-arginine dose-dependently restored concanavalin A-induced proliferation, while indomethacin and catalase had minimal effects.
• Splenic mononuclear cells from spontaneously hypertensive rats produced significantly higher levels of nitric oxide compared to controls.
• L-arginine addition diminished cell proliferation and increased nitric oxide production, and antibodies to interferon gamma partially reduced NO accumulation.

Conclusions:

• The immune depression observed in spontaneously hypertensive rats is dependent on nitric oxide production.
• Macrophages in spontaneously hypertensive rats contribute to immune dysfunction through excessive nitric oxide generation.
• Interferon gamma plays a partial role in enhancing nitric oxide production in these stimulated immune cells.