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

Biochem Biophys Res Commun. 2012 Feb 24;418(4):676-81. doi: 10.1016/j.bbrc.2012.01.076. Epub 2012 Jan 24.

Abstract

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 (10nM, 30min pretreatment) had no influence on the noradrenaline- and 5-hydroxytryptamine-induced concentration-dependent contractions. Chronic treatment of mesenteric artery with nesfatin-1 (10nM, 3days) using organ-culture method had also no influence on the agonists-induced contractions. In contrast, nesfatin-1 (10nM, 30min) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipokines / pharmacology
  • Adipokines / physiology*
  • Animals
  • Antihypertensive Agents / pharmacology
  • Blood Pressure / drug effects
  • Blood Pressure / physiology*
  • Calcium-Binding Proteins / pharmacology
  • Calcium-Binding Proteins / physiology*
  • Cyclic GMP / metabolism
  • DNA-Binding Proteins / pharmacology
  • DNA-Binding Proteins / physiology*
  • Hypothalamus / physiology
  • Male
  • Mesenteric Arteries / drug effects
  • Mesenteric Arteries / physiology
  • Muscle Contraction / drug effects
  • Muscle Contraction / physiology*
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / physiology
  • Nerve Tissue Proteins / pharmacology
  • Nerve Tissue Proteins / physiology*
  • Nitroprusside / pharmacology
  • Nucleobindins
  • Organ Culture Techniques
  • Rats
  • Rats, Wistar
  • Vascular Resistance / drug effects
  • Vascular Resistance / physiology*
  • Vasoconstriction / drug effects
  • Vasoconstriction / physiology*
  • Vasodilation / drug effects
  • Vasodilation / physiology*
  • Vasodilator Agents / pharmacology

Substances

  • Adipokines
  • Antihypertensive Agents
  • Calcium-Binding Proteins
  • DNA-Binding Proteins
  • Nerve Tissue Proteins
  • Nucb1 protein, rat
  • Nucleobindins
  • Vasodilator Agents
  • Nitroprusside
  • Cyclic GMP