IY Lee, CC Lee, CK Chang, CH Chien and MT Lin

Abstract

There is evidence that the induction of inducible nitric oxide synthase (iNOS) and peroxynitrite by ischaemia/reperfusion may lead to renal cell injury. Herein, we investigated whether Sheng mai san (SMS), a Chinese herbal medicine, protects against renal ischaemic injury during heat stroke by reducing iNOS-dependent nitric oxide (NO) and peroxynitrite formation.

Urethane-anaesthetized rats were exposed to heat stress (ambient temperature 43ºC) to induce heat stroke. Control rats were exposed to 24ºC. Mean arterial pressure and renal blood flow after the onset of heat stroke were significantly lower in heat stroke rats than in control rats. However, both colonic temperature and renal damage score were greater in heat stroke rats compared with control rats. Similarly, plasma NO, creatinine and blood urea nitrogen (BUN), as well as the renal immunoreactivity of iNOS and peroxynitrite, were significantly higher in heat stroke rats compared with their normothermic controls.

Pretreatment with SMS (1.2 g/day per rat for 7 consecutive days before the initiation of heat stress) significantly attenuated the heat stroke-induced arterial hypotension, hyperthermia, renal ischaemia and damage, the increased renal immunoreactivity of iNOS and peroxynitrite and the increased plasma levels of NO, creatinine and BUN. Pretreatment with SMS resulted in a prolongation of survival time in heat stroke.

The results of the present study suggest that SMS protects against renal ischaemic damage by reducing iNOS-dependent NO and peroxynitrite production during heat stroke.

Key words: blood urea nitrogen, creatinine, heat stroke, nitric oxide, peroxynitrite, renal ischaemia, Sheng mai san.

1. Introduction
2. Methods
   1. Material: The SMS preparation used in the present study was kindly prepared by Sun Ten Pharmaceutical (Taipei, Taiwan).
   2. Experimental animals
   3. Surgery and physiological parameters monitoring
   4. Renal histology and morphological evaluation
   5. Measurements of NO levels in plasma
   6. Immunohistochemical staining
   7. Statistical analysis
3. Results
   1. Effects of heat exposure on survival time
   2. Effects of heat exposure on physiological and biochemical parameters
   3. Effects of heat exposure on both iNOS and ONOO–expression in renal tissues
   4. Effects of heat exposure on renal pathology
4. Discussion
5. References

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