The aim of the present study was to ascertain whether the possible occurrence of overproduction of
inducible nitric oxide synthase (iNOS)-dependent
nitric oxide (NO) in the brain and inflammatory
cytokines in the peripheral blood exhibited during
heat stroke can be reduced by prior administration of
Shengmai San, a Chinese herbal medicine.
Aminoguanidine, an iNOS inhibitor, was evaluated at the same time as a reference (positive control).
Urethane-anesthetized rats were exposed to heat stress (ambient temperature of 43 degrees C) to induce
heat stroke. Control rats were exposed to 24 degrees C. Mean arterial pressure and cerebral blood flow after the onset of
heat stroke were all significantly lower than in control rats. However, cerebral iNOS immunoreactivity and NO levels were all greater after the onset of
heat stroke. The serum levels of
interleukin-1beta,
interleukin-6, and
tumor necrosis factor-alpha were all increased after the onset of
heat stroke.
Shengmai San (1.2 g/ml per rat) or
aminoguanidine (30 micromol/ml per rat) was administered orally, daily, and consecutively for 7 days before the initiation of heat stress; and this significantly attenuated the heat stress-induced arterial
hypotension,
cerebral ischemia, and increased levels of brain iNOS-dependent NO production and serum
cytokines formation.
Shengmai San shared with the
aminoguanidine almost the same efficacy in reducing iNOS-dependent NO and
cytokines overproduction during
heat stroke. These results suggest that
Shengmai San or
aminoguanidine protects against
heat stroke-induced arterial
hypotension and
cerebral ischemia by inhibition of iNOS-dependent NO overproduction in the brain and excessive accumulation of several inflammatory
cytokines in the peripheral blood stream.