Gender Differences in Sepsis‐Induced Nitric Oxide and EDHF Signaling Pathways in Rat Aorta

Abstract

Despite recent advances in managing sepsis, it still remains a major health concern in the US. Sepsis is characterized by systemic hypotension, pulmonary hypertension and refractoriness of the vasculature to contractile factors. Nitric Oxide (NO) and Endothelium‐Dependent Hyperpolarizing Factor (EDHF) are crucial in the regulation of vascular tone. The influence of gender on endothelial function in sepsis remains unknown. Therefore, this study was aimed to investigate the influence of gender on sepsis‐induced NO and EDHF signaling pathways in rat aorta. Results indicate that NO and EDHF play a major role in sepsis‐induced endothelial dysfunction in rat aorta in a experimental model of sepsis. Sepsis was induced in rats by cecal ligation and puncture (CLP). 18h after surgery septic rats showed increase in rectal temperature, neutrophilia, pulmonary edema and an increase in plasma nitrate/nitrite levels. However, mean arterial pressure was decreased. Arterial vasoreactivity was measured using an isometric tension protocol. Phenylephrine (PE) was more potent in contracting aortic rings from female than male rats, but the amplitude of contraction was identical in both the sexes. Sepsis significantly decreased the efficacy of PE in aortas from both the sexes. Acetylcholine (ACh) elicited concentration‐dependent relaxation in endothelium intact aortas from male and female rats. Sepsis had no significant effect on the endothelium‐dependent relaxation in the female aorta, but caused significant reduction in the maximal response to ACh in male aortas. There was no evidence of EDHF activity in aortic rings from either sex. Sodium nitroprusside (SNP) was more potent in dilating aortas from male than female rats. Sepsis had no significant effect on the potency or efficacy of SNP‐induced dilation in both genders. Real time PCR was used to measure mRNA expression levels of potassium channels important in the endothelium. In conclusion, the results of present study suggest that sepsis‐induced alteration in the reactivity of aorta to vasoconstrictors or vasodilators is dependent on the gender of the animal.