The Hyporesponsiveness to Norepinephrine and Inflammation in Rats with Heatstroke: Their Improvement by Hydrocortisone / 解放军医学杂志

ABSTRACT

[Abstract] Objective To monitor the hyporesponsiveness to norepinephrine in heatstroke rats and the improvement of the responsiveness and inflammation by hydrocortisone. Methods Rats were randomized into 4 groups, saline control group, saline heatstroke group, hydrocortisone control group, and hydrocortisone heatstroke group. The carotid blood pressure was monitored in the four groups of rats under anesthesia. The following three parts of experiments were conducted with the sample size 8 in each part of the experiment. (1) The experiment of noradrenaline at two loading doses (1 μg/kg) i.v.. The mean arterial pressure (MAP) and interval time between blood pressure rising and dropping to the baseline were observed in groups of rats after receiving two loading doses of noradrenaline. (2) The experiment of constant low-dose norepinephrine [25 μg/(kg.h)] by continuous pumping injection. The blood pressure level and survival time were observed. (3) The experiment to detect biochemical indicators related to responsiveness. Four groups of rats receiving constant low-dose norepinephrine were sacrificed, and the serum and aortic tissues were collected to measure serum vasodilators (nitric oxide and prostaglandin E2), hormones (cortisol and adrenocorticotropic hormone), pro-inflammatory factors (nuclear factor κB, tumor necrosis factor α, and interleukin 1β) and α1 adrenergic receptor mRNA expression levels in aortic tissues. Results (1) Compared with the saline control group, the mean arterial pressure and interval time between blood pressure rising and dropping to the baseline were significantly decreased in the saline heatstroke group after receiving noradrenaline injection at a loading dose compared with the normal saline control group, especially after the second dose. The hydrocortisone heatstroke group had higher MAP and longer interval time than the saline heatstroke group. The difference was statistically significant (P<0.05). (2) The mean arterial pressure level of the saline heatstroke group was significantly lower than that of the saline control group after receiving a constant low dose of norepinephrine. The mean arterial pressure in the hydrocortisone heatstroke group was increased compared with the saline heatstroke group, and the survival time was prolonged. The difference was statistically significant (P<0.05). (3) The serum nitric oxide, prostaglandin E2, cortisol, and adrenocorticotropic hormone of the saline heatstroke group were not significantly different from those of the saline control group. The levels of pro-inflammatory factors were significantly increased, and the mRNA levels of α1 adrenergic receptors in the aorta were significantly reduced in the saline heatstroke group compared with the saline control group. The decreased pro-inflammatory factors and increased mRNA of α1 adrenergic receptors in the aorta were observed in the hydrocortisone heatstroke group compared with the saline heatstroke group. The difference was statistically significant (P<0.05). Conclusions The hyporesponsiveness to norepinephrine was demonstrated in the heatstroke rats with circulatory failure. Hydrocortisone could increase MAP and survival time, improve the hyporesponsiveness, reduce the inflammatory cytokines and increase the aortic adrenergic receptor expression.