A novel adipocytokine, nesfatin-1 modulates peripheral arterial contractility and blood pressure in rats

Nesfatin-1 is a novel adipocytokine which exerts not only anorexigenic but also hypertensive roles through acting on hypothalamus melanocortin-3/4 receptors. Although it is logical to hypothesize that nesfatin-1 could also affect the contractile reactivity of peripheral blood vessels, it still remains to be examined. The present study was performed to test the hypothesis. In both endothelium-intact and -denuded mesenteric artery of rats, acute treatment with nesfatin-1 (10 nM, 30 min pretreatment) had no influence on the noradrenaline- and 5-hydroxytryptamine-induced concentration-dependent contractions. Chronic treatment of mesenteric artery with nesfatin-1 (10 nM, 3 days) using organ-culture method had also no influence on the agonists-induced contractions. In contrast, nesfatin-1 (10 nM, 30 min) significantly inhibited the sodium nitroprusside (SNP)-induced relaxations of smooth muscle in mesenteric artery. A membrane permeable cyclic GMP (cGMP) analog, 8-bromo-cGMP-induced relaxations were not affected by nesfatin-1. Consistently, the SNP-induced cGMP production in smooth muscle was impaired by nesfatin-1. Intravenous application of nesfatin-1 to rats not only increased blood pressure but also impaired the SNP-induced decreases in blood pressure. The present study for the first time reveals that nesfatin-1 affects peripheral arterial blood vessel and inhibits the nitric oxide donor-induced smooth muscle relaxations via impairing the cGMP production. The results are the first to demonstrate that nesfatin-1 modulates blood pressure through directly acting on peripheral arterial resistance.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Nesfatin-1 is a novel adipocytokine with hypertensive effects through acting on central nerves. ► Effects of nesfatin-1 on contractility of peripheral blood vessels remain to be examined. ► Nesfatin-1 inhibited both smooth muscle relaxations and cyclic GMP production induced by sodium nitroprusside. ► Intravenous nesfatin-1 treatment increased blood pressure in rats. ► The results are the first to determine the effects of nesfatin-1 on peripheral blood vessel.