Prior Antagonism of Endothelin-1A Receptors Alleviates Circulatory Shock and Cerebral Ischemia During Rat Heatstroke

Liu, Chia-Chyuan; Chen, Zhih‐Cherng; Cheng, Bingqing; Lin, Mao‐Tsun

doi:10.1254/jphs.fp0040203

Cited by 16 publications

(17 citation statements)

References 46 publications

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“…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.…”

Section: Discussionmentioning

confidence: 49%

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

et al. 2005

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Abstract. The aim of this study was to investigate the effect of Shengmai San (SMS), a traditional Chinese herbal medicine, on heatstroke-induced circulatory shock and oxidative damage in the brain in rats. Anesthetized rats were exposed to a high ambient temperature (43°C) to induce heatstroke. After the onset of heatstroke, the values of mean arterial pressure, cerebral perfusion pressure, cerebral blood flow, and brain partial pressure of O 2 were all significantly lower than those in normothermic controls. However, the values of intracranial pressure, brain and colonic temperatures, and brain levels of free radicals, lipid peroxidation, and cellular ischemia and damage markers were all greater in heatstroke rats compared with those of normothermic controls. Pretreatment or post-treatment with SMS significantly reduced the hypotension, intracranial hypertension, cerebral hypoperfusion and hypoxia and increased levels of ischemia and damage markers in the brain during heatstroke. The protective effects exerted by SMS pretreatment is superior to those of SMS post-treatment. The results demonstrate that SMS is effective for prevention and repair of circulatory shock and ischemic and oxidative damage in the brain during heatstroke.

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Section: Discussionmentioning

confidence: 49%

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

et al. 2005

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“…Animals, under urethane anesthesia, were positioned in a stereotoxic apparatus (model 1460; David Kopf Instruments, Tujunga, CA, USA) to insert a probe for measurement of local CBF in the striatum (5). A 100-µm-diameter thermocouple and two 230-µm fibers were attached to the oxygen probe.…”

Section: Cbf Monitoringmentioning

confidence: 99%

“…Intestinal mucosal permeability to endotoxin increases in heat stressed rats (4) and lead to production of inflammatory cytokines that induce release of nitric oxide (NO) (3) and endothelins (5). Both pyrogenic cytokines and endothelin-derived factors can precipitate arterial hypotension, hyperthermia, and cerebral ischemia during heatstroke (5 -7).…”

Section: Introductionmentioning

confidence: 99%

Shengmai San, a Chinese Herbal Medicine Protects Against Rat Heat Stroke by Reducing Inflammatory Cytokines and Nitric Oxide Formation

Wang¹,

Chang²,

Liou³

et al. 2005

J Pharmacol Sci

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Abstract. 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). Urethaneanesthetized rats were exposed to heat stress (ambient temperature of 43°C) to induce heat stroke. Control rats were exposed to 24°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-1β, interleukin-6, and tumor necrosis factor-α were all increased after the onset of heat stroke. Shengmai San (1.2 g / ml per rat) or aminoguanidine (30 µmol / 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 iNOSdependent 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.

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“…Overproduction of NO may contribute to the splanchnic vasodilation that precedes vascular collapses with heatstroke. Our previous results have further shown that in addition to overproduction of NOx in brain, decreased cardiac output (due to decreased total peripheral vascular resistance and stroke volume), intracranial hypertension, and cerebral ischemia and hypoxia, and hyperthermia occur during heatstroke in the rat (10,11,21). Our previous findings have also shown that accumulation of large amounts of reactive oxygen species in various organs including the kidney and the brain is associated with hyperthermia, arterial hypotension, and cerebral ischemia and injury during heatstroke (22,23).…”

Section: Discussionmentioning

confidence: 70%

“…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).…”

Section: Introductionmentioning

confidence: 99%

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

Lee¹,

Lee²,

Chang³

et al. 2005

J Pharmacol Sci

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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.

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Prior Antagonism of Endothelin-1A Receptors Alleviates Circulatory Shock and Cerebral Ischemia During Rat Heatstroke

Cited by 16 publications

References 46 publications

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

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

Shengmai San, a Chinese Herbal Medicine Protects Against Rat Heat Stroke by Reducing Inflammatory Cytokines and Nitric Oxide Formation

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

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