Aminoguanidine Protects Against Intracranial Hypertension and Cerebral Ischemic Injury in Experimental Heatstroke

Abstract

Abstract. The aim of the present study was to ascertain whether aminoguanidine attenuated intracranial hypertension and cerebral ischemic injury in experimental heatstroke. Urethaneanesthetized rats were exposed to heat stress (ambient temperature of 43°C) to induce heatstroke. Control rats were exposed to 24°C. Mean arterial pressure, cerebral perfusion pressure, and cerebral blood flow after the onset of heatstroke were all significantly lower than in control rats. However, colonic temperature, intracranial pressure, heart rate, cerebral inducible nitric oxide synthase (iNOS)-dependent NO, and neuronal damage score were greater after the onset of heatstroke. Aminoguanidine (30 mmol / kg, i.v.; 30 min before the start of heat exposure) pretreatment significantly attenuated the heatstroke-induced hyperthermia, arterial hypotension, intracranial hypertension, cerebral ischemia and neuronal damage, and increased iNOS-dependent NO formation in the brain. The extracellular concentrations of ischemic (e.g., glutamate and lactate / pyruvate ratio) and damage (e.g., glycerol) markers in the hypothalamus were also increased after the onset of heatstroke. Aminoguanidine pretreatment significantly attenuated the increase in hypothalamic ischemia and damage markers associated with heatstroke. Delaying onset of aminoguanidine administration (i.e., 0 or 30 min after the start of heat exposure) reduced the preventive efficiency on heatstroke-induced hyperthermia, arterial hypotension, intracranial hypertension, cerebral ischemia, and increased iNOS-dependent NO formation in brain. These results suggest that aminoguanidine protects against heatstroke-induced intracranial hypertension and cerebral ischemic injury by inhibition of cerebral iNOS-dependent NO production.

Chinese Herbal Medicine, Shengmai San, Is Effective for Improving Circulatory Shock and Oxidative Damage in the Brain During Heatstroke

“…Indeed, both present and previous (26,27) results have shown that both cerebral ischemia and injury that occurred during heatstroke are associated with an increased production of glycerol, lactate / pyruvate ratio, and glutamate in the brain. Our results further demonstrated that PO 2 in the rat brain was greatly reduced after the onset of heatstroke.…”

Human Umbilical Cord Blood–Derived CD34+ Cells Can Be Used as a Prophylactic Agent for Experimental Heatstroke

“…Indeed, the NO overproduction could be observed (ref. 5 and the present results) and iNOS inhibitors (30) …”

“…Indeed, plasma or cerebral levels of NO are elevated in heatstroke rats (27,28; present results). Aminoguanidine, an inducible nitric oxide synthase (iNOS) inhibitor, improves heat tolerance in the rat by preserving the splanchnic blood flow (29) and reducing intracranial hypertension and cerebral ischemia and damage (30). An early exposure to HUCBC (5), in addition to ameliorating iNOS-dependent NO overproduction in brain, causes attenuation of cerebrovascular dysfunction or injury that occurred during heatstroke in the rat.…”

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

“…Both pyrogenic cytokines can interfere with normal thermoregulation, thereby precipitating arterial hypotension, hyperthermia, and heatstroke (1). Recent reports have also shown that aminoguanide, an iNOS inhibitor, slows the rate of NO production, preserves the splanchnic (8) and cerebral blood flow (10), and improves heat tolerance in rats. However, relative little evidence is available about the effects of iNOS inhibition on the renal ischemia and damage during heatstroke.…”

“…This alteration allows leakage of endotoxins and increases production of inflammatory cytokines that induce release of NO and endothelins (10,11). Both pyrogenic cytokines can interfere with normal thermoregulation, thereby precipitating arterial hypotension, hyperthermia, and heatstroke (1).…”