Front Pharmacol. 2018 May 22;9:528. doi: 10.3389/fphar.2018.00528. eCollection 2018.
Activation of eNOS by D-pinitol Induces an Endothelium-Dependent Vasodilatation in Mouse Mesenteric Artery.
Frontiers in pharmacology
Luciana N Moreira, Josiane F Silva, Grazielle C Silva, Virgínia S Lemos, Steyner F Cortes
Affiliations
Affiliations
- Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
- Department of Physiology and Biophysics, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
PMID: 29872397
PMCID: PMC5972298 DOI: 10.3389/fphar.2018.00528
Abstract
D-pinitol is a cyclitol present in several edible plant species and extensively investigated for the treatment of metabolic diseases in humans, as food supplement, and demonstrated protective effects in the cardiovascular system. For these reasons, the present work aimed at investigating the mechanisms involved in the vascular effects of D-pinitol in mouse mesenteric artery. Mesenteric arteries from male C57BL/6 mice were mounted in a wire myograph. Nitrite was measured by the 2,3-diaminonaphthalene (DAN) method. Protein expression and phosphorylation were measured by Western blot. The systolic blood pressure (SBP) was measured by tail-cuff plethysmography. D-pinitol induced a concentration-dependent vasodilatation in endothelium-intact, but not in endothelium-denuded arteries. Nω-Nitro-L-arginine methyl ester (300 μM) abolished the effect of D-pinitol, while 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 10 μM) shifted the concentration-response curve to the right. KN-93 (1 μM) blunted the vasodilator effect of D-pinitol, but H-89 (0.1 μM) did not change it. 1-[2-(Trifluoromethyl) phenyl]imidazole (300 μM), indomethacin (10 μM), celecoxib (5 μM), wortmannin (1 μM), ruthenium red (10 μM), tiron (10 μM), MnTMPyP (30 μM), MPP (0.1 μM), PHTPP (0.1 μM), and atropine (1 μM) did not change the effect of D-pinitol. D-pinitol increased the concentration of nitrite, which was inhibited by L-NAME and calmidazolium (10 μM). D-pinitol increased the phosphorylation level of eNOS activation site at Ser
Keywords: D-pinitol; calcium-calmodulin complex; endothelium; mesenteric artery; nitric oxide synthase
References
- J Physiol. 1988 Apr;398:277-89 - PubMed
- Am J Physiol Heart Circ Physiol. 2003 Jun;284(6):H2311-9 - PubMed
- Clin Sci (Lond). 2016 Jun 1;130(11):895-906 - PubMed
- Angew Chem Int Ed Engl. 2016 Jan 26;55(5):1614-50 - PubMed
- Proc Natl Acad Sci U S A. 2006 Jan 3;103(1):218-23 - PubMed
- Am J Physiol Heart Circ Physiol. 2008 Dec;295(6):H2503-11 - PubMed
- Diabetes Care. 2000 Jul;23(7):1000-5 - PubMed
- Hypertension. 2003 Apr;41(4):879-81 - PubMed
- Eur J Obstet Gynecol Reprod Biol. 2015 Dec;195:72-6 - PubMed
- Eur J Clin Nutr. 2005 Mar;59(3):456-8 - PubMed
- Biochem Biophys Res Commun. 2002 Jan 25;290(3):909-13 - PubMed
- Biochemistry. 1996 Nov 19;35(46):14651-8 - PubMed
- Nature. 1999 Jun 10;399(6736):597-601 - PubMed
- FEBS Lett. 1990 Jun 4;265(1-2):133-6 - PubMed
- J Cardiovasc Pharmacol. 2005 Sep;46(3):274-9 - PubMed
- Biochem J. 1993 Dec 1;296 ( Pt 2):297-301 - PubMed
- J Smooth Muscle Res. 2003 Dec;39(6):249-67 - PubMed
- Eur J Pharmacol. 2010 Sep 25;643(2-3):260-6 - PubMed
- Nature. 1999 Jun 10;399(6736):601-5 - PubMed
- Circulation. 2001 Mar 13;103(10):1410-5 - PubMed
- Ann Nutr Metab. 2012;60(1):1-5 - PubMed
- Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6252-6 - PubMed
- Circ Res. 2009 Jul 17;105(2):114-27 - PubMed
- J Biol Chem. 1999 Oct 15;274(42):30101-8 - PubMed
- Circ Res. 2001 Jun 8;88(11):E68-75 - PubMed
- Br J Pharmacol. 2000 Aug;130(8):1944-8 - PubMed
- Atherosclerosis. 2006 Apr;185(2):227-39 - PubMed
- J Exp Med. 2008 Sep 1;205(9):2053-63 - PubMed
- Cell Calcium. 2005 Sep-Oct;38(3-4):233-52 - PubMed
- Peptides. 2003 Mar;24(3):455-62 - PubMed
- Nat Rev Cardiol. 2012 May 22;9(8):439-53 - PubMed
- Curr Diab Rep. 2016 Mar;16(3):30 - PubMed
- Jpn J Pharmacol. 2001 Aug;86(4):369-75 - PubMed
- J Pharmacol Exp Ther. 2011 Mar;336(3):701-8 - PubMed
- Biosci Biotechnol Biochem. 2010;74(5):1062-7 - PubMed
- Eur Heart J. 2012 Apr;33(7):829-37, 837a-837d - PubMed
- J Nutr. 2004 Nov;134(11):2998-3003 - PubMed
- Annu Rev Physiol. 2006;68:685-717 - PubMed
- Circ Res. 2007 Feb 2;100(2):158-73 - PubMed
- Hypertension. 2009 Mar;53(3):532-8 - PubMed
- Biochimie. 2013 Oct;95(10):1811-27 - PubMed
- Pflugers Arch. 2010 May;459(6):793-806 - PubMed
- J Med Food. 2006 Summer;9(2):182-6 - PubMed
Publication Types