Agmatinin Deneysel Sıçan Septik Şok Modelinde Bozulmuş Vasküler Yanıta Etkisi

Abstract

Sepsis is the inflammatory response of the host to pathogen. Regardless of the severity of inflammation, mortality is observed as a result of impaired hemodynamic homeostasis-mediated organ dysfunction. Therefore, treatment protocols that support the cardiovascular system contribute to the prognosis. The need for protocols that support and also reduce the concentrations of current treatments is necessary as the current protocols lose their efficacy over time and also affect beneficial pathways. Agmatine is an imidazoline receptor agonist, α2-adrenergic receptor modulator and nitric oxide synthase inhibitor. It can increase blood pressure through the central nervous system. It causes vasodilation with its direct effect on peripheral vascular structure. The effect of two different doses of agmatine (3 mg/kg and 10 mg/kg) was examined in a 4 mg/kg intraperitoneal lipopolysaccharide injection model that can produce the hypodynamic profile of septic shock (low blood pressure, persistent vasoconstriction) in rats. After lipopolysaccharide injection, in vivo mean blood pressure measured from femoral artery, norepinephrine responses and blood flow measured from superior mesenteric artery were decreased; dose-dependent phenylephrine, acetylcholine ex vivo response was suppressed in abdominal aorta and thoracic aorta preparations. Serum TNF-α and IL-1β concentrations were increased. In the groups administered lipopolysaccharide followed by agmatine, blood flow were increased; suppressed norepinephrine response or phenylephrine and acetylcholine responses in the abdominal aorta preparation were restored. There was no effect of agmatine on serum TNF-α and IL-1β. Agmatine may provide hemodynamic homeostasis in sepsis by restoring mesenteric blood flow and regulating the response profile of the vascular structure.