Selective Inhibition of Inducible Nitric Oxide Synthase Attenuates Renal Ischemia and Damage in Experimental Heatstroke

Abstract

Abstract. 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°C) to induce heatstroke. Control rats were exposed to 24°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.

CEREBROVASCULAR DYSFUNCTION IS AN ATTRACTIVE TARGET FOR THERAPY IN HEAT STROKE¶

“…Our results further showed that pretreatment with aminoguanidine, an inhibitor of inducible nitric oxide synthase (iNOS), significantly reduced the heat stroke‐induced hyperthermia, arterial hypotension, intracranial hypertension, cerebral ischaemia and increased iNOS‐dependent NO formation in the brain 77 . l ‐ N 6‐(1‐Iminoethyl) lysine ( l ‐NIL), a relatively selective iNOS inhibitor, 78,79 has also been shown to protect against renal ischaemia and damage during heat stroke by reducing hyperthermia and arterial hypotension in rats 80 …”

NADPH-diaphorase activity in the central nervous system of the Gray mussel Crenomytilus grayanus (Dunker) under stress conditions: A histochemical study

“…2008.03.001 in adaptive responses of an organism to stress conditions. NO production may be altered by a variety of stressors including restraint (Masood et al, 2004), immobilization (Shirakawa et al, 2004), hypoxia (Manukhina et al, 2000), hypo-and hyperthermia (Han et al, 2002;Lee et al, 2005), pain shock (Aley et al, 1998), and physical training (Green et al, 2004; see also a review by Malyshev and Manukhina, 1998).…”

Death receptors mediate the adverse effects of febrile-range hyperthermia on the outcome of lipopolysaccharide-induced lung injury

“…Although hyperthermia in the range of heat shock (43°C) can directly induce NO synthase and cause systemic hypotension and death in a rat model of heat stroke, our model of fever-range hyperthermia did not independently affect plasma concentration of NO metabolites (23,41). This study does not address whether the increased NO concentration observed in the mice exposed to hyperthermia and LPS was attributable to direct induction of NO synthase or the effect of increased production of inflammatory cytokines in the peripheral blood leukocytes.…”