The aim of the present study was to determine whether the possible occurrence of renal
ischemia and damage during
heatstroke can be suppressed by prior administration of L-N6-(1-iminoethyl)
lysine (L-NIL), a selective
inducible nitric oxide synthase (iNOS) inhibitor.
Urethane-anesthetized rats were exposed to heat stress (43 degrees C) to induce
heatstroke. Control rats were exposed to 24 degrees C. Mean arterial pressure and renal blood flow after the onset of
heatstroke both were significantly lower in vehicle-treated
heatstroke rats than in normothermic controls. However, both the body temperature and renal damage scores were greater in vehicle-treated
heatstroke rats compared with normothermic controls. Plasma
nitric oxide (NO),
creatinine, and blood
urea nitrogen (BUN), as well as the renal immunoreactivity of iNOS and
peroxynitrite all were significantly higher in vehicle-treated
heatstroke rats compared with their normothermic controls. Pretreatment with L-NIL (3 mg/kg, administered intravenously and immediately at the onset of heat stress) significantly attenuated
heatstroke-
induced hyperthermia, arterial
hypotension, renal
ischemia and damage, increased renal levels of immunoreactivity of iNOS and
peroxynitrite, and increased plasma levels of NO,
creatinine, and BUN. Accordingly, pretreatment with L-NIL significantly improved survival during
heatstroke. The results suggest that selective inhibition of iNOS-dependent NO and
peroxynitrite formation protects against renal
ischemia and damage during
heatstroke by reducing
hyperthermia and arterial
hypotension.