Stress Preconditioning Effects on Heart Rate and Blood Pressure under Circumstances of Gastric and Small Intestine Injury Induced by Indomethacin in Conscious Rats

Abstract

Nonsteroidal anti‐inflammatory drugs (NSAIDs) are commonly used medications. However NSAIDs exert side effects not only in the stomach and the small intestine but also in cardiovascular system. A disorder of the circadian heart rate (HR) under circumstances of indomethacin (IM)‐induced gastric and small intestinal injury is potentially lethal factor and our previous experimental findings confirmed this fact. Preconditioning is one of perspective approaches to protect the heart and other organs against adverse influences. We demonstrated previously that glucocorticoids released during mild stress contribute to protection of the gastric mucosa against severe stress through maintaining various links of the general body homeostasis, including blood pressure (BP). Here we studied the effects of stress preconditioning on HR and BP under circumstances of gastric and small intestine injury induced by IM in conscious rats. Preliminary fasting (24 h) rats were subjected IM (35 mg/kg, sc) administration with preconditioning stress (cold‐restraint, 10 °C, 30 min and keeping at room temperature 1 h before IM administration) or without it. HR and BP were measured by non‐invasive tail cuff method before IM injection and 4, 24 and 48 h after IM administration in stressed and non‐stressed animals. The gastric and the small intestinal mucosa were examined for injury 4 h (formation of the gastric erosions) and 24 and 48 h (formation of the small intestinal injury) after IM administration. Plasma corticosterone levels were also measured. IM administration induced formation of gastric erosions (4 h after its injection) and their healing for 48 h was followed by a development of the small intestinal injury. Formation of gastric erosions caused an elevation of corticosterone levels 4 h after IM; their following healing resulted in a decrease of IM‐induced corticosterone levels 24 and 48 h after IM injection till baseline level. IM‐induced gastrointestinal injury was accompanied by a gradual decrease of systolic BP and increase of the HR for 48 h after IM. Preconditioning stress reduced IM‐induced gastric erosions as well as small intestinal injury 4 and 24 h after its injection, respectively, and recovered HR and systolic BP 48 h after IM. Thus, the data suggest that preconditioning stress may reduce the vulnerability of the gastric and the small intestinal mucosa to ulcerogenic action of IM and stabilizes the hemodynamic parameters.Support or Funding InformationThe study was supported by grant of Russian Science Foundation (RSF) N 19‐15‐00430.