Biochemical and Biophysical Research Communications
A novel adipocytokine, nesfatin-1 modulates peripheral arterial contractility and blood pressure in rats
Graphical abstract
Highlights
► 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.
Introduction
Nesfatin-1 is a novel hypothalamus nucleobindin 2-derived peptide which is distributed in the regions including arcuate nuclei, paraventricular nuclei, supraoptic nuclei, and lateral hypothalamic areas [1], [2], [3]. Intracerebroventricular injection of nesfatin-1 to rats or intraperitoneal application to mice reduced the food intake [1], [4], [5], suggesting that nesfatin-1 is an anorexigenic hormone. Anorexigenic effect of nesfatin-1 is thought to be mediated primary via activating melanocortin-3/4 receptors in hypothalamus [1]. In addition, nesfatin-1 is suggested to regulate functions of other brain-derived hormones, since nesfatin-1 protein in neurons was found to co-localize with various hormones such as vasopressin, oxytocin, thyrotropin-releasing hormone, corticotropin-releasing hormone, somatostatin, neurotensin, growth-hormone-releasing hormone, and pro-opiomelanocortin [6]. On the other hand, nesfatin-1 was recently identified in the adipocytes of mice and humans, and its expression level correlated positively with the parameter of obesity in humans [7]. Accumulating evidence indicates that adipocytes-derived hormones termed adipocytokines can affect the contractile reactivity of peripheral blood vessels and participate in the control of blood pressure (BP) [2], [3]. For example, our group has recently demonstrated that an adipocytokine, visfatin [8] and omentin [9] caused a nitric oxide-mediated endothelium-dependent relaxation in rat isolated blood vessels. In addition, it was recently demonstrated that intracerebroventricularly injected nesfatin-1 can increase a mean arterial BP in conscious rats via the activation of sympathetic nerves through acting on hypothalamus melanocortin-3/4 receptors [4]. However, it still remains to be examined whether nesfatin-1 could affect the contractile reactivity of peripheral blood vessels. In the present study, we examined effects of nesfatin-1 on contractility of rat isolated mesenteric artery and BP.
Section snippets
Tissue preparation
Male Wistar rats (205–370 g, 7–20-week-old) were anesthetized with urethane (1.5 g/kg, i.p.) and euthanized by exsanguination. The main branch of superior mesenteric artery was isolated [8], [9]. After removal of fat and adventitia in normal physiological salt solution (PSS), the mesenteric artery was cut into rings (2-mm long and 1-mm in diameter) for the measurement of isometric tension. In some experiments, the endothelium was removed by rubbing the intimal surface with a flat face of a pair
Acute effects of nesfatin-1 on agonists-induced contractions in rat isolated mesenteric artery
We first examined effects of acute treatment with nesfatin-1 on smooth muscle contractions induced by contractile agonists, which may be responsible for the BP control. In both endothelium-intact (End (+)) and -denuded (End (−)) mesenteric artery, NA (1 nM to 1 μM) induced contractions in a concentration-dependent manner (Fig. 1A, B, open circle). Pretreatment of End (+) and End (−) mesenteric artery with nesfatin-1 (10 nM, 30 min) had no effect on the NA-induced contractions (Fig. 1A, B, closed
Discussion
In the present study, we examined effects of a novel adipocytokine, nesfatin-1 on contractility of rat isolated mesenteric artery. The major finding of the study is that nesfatin-1 specifically impairs the NO donor, SNP-induced relaxation of smooth muscle via impairing the cGMP production. It was also shown that intravenous application of nesfatin-1 to rats not only increased the BP but also impaired the SNP-induced decreases in BP. The results are the first to determine the effects of
Acknowledgments
This study was supported in part by a Grant for Scientific Research from the Kitasato University, School of Veterinary Medicine and a Kitasato University Research Grant for Young Researchers.
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2020, Biochemical and Biophysical Research CommunicationsCitation Excerpt :The polypeptide consists of 82 amino acids, whose central part, nesfatin-130-59, has been identified as active core able to reduce food intake after intracerebroventricular (icv) injection in mice [8,9] and rats [10]. While the food intake-reducing effect was not consistently observed following peripheral application of nesfatin-1 in rodents [9,11] peripheral nesfatin-1 is likely involved in glucose control [12], inflammation [13], cardiovascular regulation [14] and gastrointestinal motility [15]. An autoradiographic study (the nesgfatin-1 receptor is still unknown) showed widespread binding of nesfatin-1 in the periphery throughout the gastrointestinal tract and different endocrine organs [16]; therefore, additional effects of peripheral nesfatin-1 might be suspected.
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2020, Pharmacological ResearchCitation Excerpt :If administered intravenously, it increases arterial peripheral resistance by acting on arterioles [91]. It is also able to directly inhibit the sodium nitroprusside-induced cGMP production, preventing smooth muscle relaxation [91]. Osaki and Shimizu [92] observed that a peripheral administration of Nesfatin-1 significantly increases mean blood pressure in mice without increasing the heart rate.