Evaluating nesfatin-1 effects on heart rate and vascular response

Objective: Recent studies have shown that perivascular adipose tissue (PVAT) modulated vascular smooth muscle reactivity by releasing several mediators called adipokines. One of the novel adipokines secreted by PVAT is nesfatin-1. Although nesfatin-1 is widely expressed in various peripheral tissues, direct effects of nesfatin-1 on cardiovascular activity in vitro are not known well. The aim of this study was to investigate the effects of nesfatin-1 on cardiovascular reactivity by using an in vitro model of rat right atrium and thoracic aorta. Method: The first set of experiments were conducted on right atria isolated from adult rats. The contractile and chronotropic effects of nesfatin-1 on atrial tissues were assessed in vitro. In another set of experiments, isometric tension studies were performed in isolated rat thoracic aorta in response to potassium chloride (10-80 mM), phenylephrine (10-9–10-5 M), acetylcholine (10-9–10-5 M) and sodium nitroprusside (10-11–10-6 M). High KCl solution (Ca2+-free 80 mM) was used to activate the Ca2+ entry mechanism from the extracellular space. Also, phenylephrine was used to stimulate IP3-stimulated Ca2+ release from the intracellular Ca2+ stores in the absence of extracellular Ca2+ (Ca2+-free Krebs solution). Results: Nesfatin-1 (10-100 ng/ml) produced a concentration-dependent increase in the amplitude of contractions and the beating rate. In endothelium-intact thoracic aort, nesfatin-1 caused a concentration-dependent relaxation. Also, nesfatin-1 incubation (10 ng/ml, 60 min) significantly augmented both acetylcholine- and sodium nitroprusside-induced relaxations in thoracic aorta. On the other hand, incubation of thoracic aorta rings with nesfatin-1 had no influence on the potassium chloride- and phenylephrine-induced contractions. The contractions induced by stepwise addition to Ca2+ were not significantly altered by nesfatin-1 incubation as well as contractions induced by phenylephrine in the absence of extracellular Ca2+. Conclusion: Nesfatin-1 may directly affects peripheral cardiovascular responses through directly acting on peripheral arterial resistance and on cardiac contractility