Abstract
Hydrogen sulfide has emerged as an important endothelium-dependent vasodilator, but its role in shear stress-mediated dilation of coronary arteries is unclear. We examined the role of H2S on shear stress-mediated dilation of isolated mouse coronary arteries. In these vessels, Na2S produced concentration-dependent dilation, which was significantly inhibited by iberiotoxin and by 4-aminopyridine. In addition, BK and Kv currents in mouse coronary smooth muscle cells were directly activated by Na2S, suggesting that H2S produced vasodilation through BK and Kv channel activation. Using a pressure servo controller system, freshly isolated mouse coronary arteries were subjected to physiological levels of shear stress (1 to 25 dynes/cm2) and produced graded dilatory responses, but such effects were diminished in the presence of 100 μM Na2S. Pre-incubation with the cystathionine γ-lyase inhibitor, d,l-propargylglycine (PPG), resulted in a paradoxical augmentation of shear stress-mediated vasodilation. However, in the presence of L-NAME or in coronary arteries from eNOS knockout mice, PPG inhibited shear stress-mediated vasodilation, suggesting an interaction between NO and H2S signaling. Na2S inhibited eNOS activity in cultured mouse aortic endothelial cells and reduced the level of phospho-eNOS(serine 1177). These results suggest that both NO and H2S are important shear stress-mediated vasodilators in mouse coronary arteries but there is a complex interaction between these two signaling pathways that results in paradoxical vasoconstrictive effects of H2S through inhibition of NO generation.
Similar content being viewed by others
References
Boo YC, Sorescu G, Boyd N, Shiojima I, Walsh K, Du J, Jo H (2002) Shear stress stimulates phosphorylation of endothelial nitric-oxide synthase at Ser1179 by Akt-independent mechanisms: role of protein kinase A. J Biol Chem 277:3388–3396
Braam B, de Roos R, Bluyssen H, Kemmeren P, Holstege F, Joles JA, Koomans H (2005) Nitric oxide-dependent and nitric oxide-independent transcriptional responses to high shear stress in endothelial cells. Hypertension 45:672–680
Chai Q, Wang XL, Zeldin DC, Lee HC (2013) Role of caveolae in shear stress-mediated endothelium-dependent dilation in coronary arteries. Cardiovasc Res 100:151–159
Dimmeler S, Fleming I, Fisslthaler B, Hermann C, Busse R, Zeiher AM (1999) Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation. Nature 399:601–605
Edwards G, Feletou M, Weston AH (2010) Endothelium-derived hyperpolarising factors and associated pathways: a synopsis. Pflugers Arch 459:863–879
Fleming I, Busse R (2003) Molecular mechanisms involved in the regulation of the endothelial nitric oxide synthase. Am J Physiol 284:R1–R12
Geng B, Cui Y, Zhao J, Yu F, Zhu Y, Xu G, Zhang Z, Tang C, Du J (2007) Hydrogen sulfide downregulates the aortic L-arginine/nitric oxide pathway in rats. Am J Physiol 293:R1608–R1618
Ishikawa M, Kajimura M, Adachi T, Maruyama K, Makino N, Goda N, Yamaguchi T, Sekizuka E, Suematsu M (2005) Carbon monoxide from heme oxygenase-2 is a tonic regulator against NO-dependent vasodilatation in the adult rat cerebral microcirculation. Circ Res 97:e104–e114
Jackson-Weaver O, Osmond J, Riddle MA, Naik JS, Gonzalez Bosc LV, Walker BR, Kanagy NL (2013) Hydrogen sulfide dilates rat mesenteric arteries by activating endothelial large-conductance Ca2+-activated K+ channels and smooth muscle Ca2+ sparks. Am J Physiol Heart Circ Physiol 304:H1446–H1454
Jackson-Weaver O, Paredes DA, Gonzalez Bosc LV, Walker BR, Kanagy NL (2011) Intermittent hypoxia in rats increases myogenic tone through loss of hydrogen sulfide activation of large-conductance Ca(2+)-activated potassium channels. Circ Res 108:1439–1447
Kubo S, Kurokawa Y, Doe I, Masuko T, Sekiguchi F, Kawabata A (2007) Hydrogen sulfide inhibits activity of three isoforms of recombinant nitric oxide synthase. Toxicology 241:92–97
Lacza Z, Dezsi L, Kaldi K, Horvath EM, Sandor P, Benyo Z (2003) Prostacyclin-mediated compensatory mechanism in the coronary circulation during acute NO synthase blockade. Life Sci 73:1141–1149
Levitt MD, Abdel-Rehim MS, Furne J (2011) Free and acid-labile hydrogen sulfide concentrations in mouse tissues: anomalously high free hydrogen sulfide in aortic tissue. Antioxid Redox Signal 15:373–378
Li L, Rose P, Moore PK (2011) Hydrogen sulfide and cell signaling. Annu Rev Pharmacol Toxicol 51:169–187
Liang GH, Adebiyi A, Leo MD, McNally EM, Leffler CW, Jaggar JH (2011) Hydrogen sulfide dilates cerebral arterioles by activating smooth muscle cell plasma membrane KATP channels. Am J Physiol Heart Circ Physiol 300:H2088–H2095
Liang GH, Xi Q, Leffler CW, Jaggar JH (2012) Hydrogen sulfide activates Ca(2)(+) sparks to induce cerebral arteriole dilatation. J Physiol 590:2709–2720
Loot AE, Popp R, Fisslthaler B, Vriens J, Nilius B, Fleming I (2008) Role of cytochrome P450-dependent transient receptor potential V4 activation in flow-induced vasodilatation. Cardiovasc Res 80:445–452
Lu T, Chai Q, Yu L, d’Uscio LV, Katusic ZS, He T, Lee HC (2012) Reactive oxygen species signaling facilitates FOXO-3a/FBXO-dependent vascular BK channel beta1 subunit degradation in diabetic mice. Diabetes 61:1860–1868
Lu T, Katakam PV, VanRollins M, Weintraub NL, Spector AA, Lee HC (2001) Dihydroxyeicosatrienoic acids are potent activators of Ca(2+)-activated K(+) channels in isolated rat coronary arterial myocytes. J Physiol 534:651–667
Lu T, Wang XL, He T, Zhou W, Kaduce TL, Katusic ZS, Spector AA, Lee HC (2005) Impaired arachidonic acid-mediated activation of large-conductance Ca2+-activated K+ channels in coronary arterial smooth muscle cells in Zucker Diabetic Fatty rats. Diabetes 54:2155–2163
Lu T, Zhang DM, Wang XL, He T, Wang RX, Chai Q, Katusic ZS, Lee HC (2010) Regulation of coronary arterial BK channels by caveolae-mediated angiotensin II signaling in diabetes mellitus. Circ Res 106:1164–1173
Malek A, Ahlquist R, Gibbons G, Dzau V, Izumo S (1995) A con-plate apparatus for the in vitro biochemical and molecular analysis of the effect of shear stress on adherent cells. Methods Cell Sci 17:165–176
Mendoza SA, Fang J, Gutterman DD, Wilcox DA, Bubolz AH, Li R, Suzuki M, Zhang DX (2010) TRPV4-mediated endothelial Ca2+ influx and vasodilation in response to shear stress. Am J Physiol Heart Circ Physiol 298:H466–H476
Merkus D, Sorop O, Houweling B, Boomsma F, van den Meiracker AH, Duncker DJ (2006) NO and prostanoids blunt endothelin-mediated coronary vasoconstrictor influence in exercising swine. Am J Physiol Heart Circ Physiol 291:H2075–H2081
Mustafa AK, Sikka G, Gazi SK, Steppan J, Jung SM, Bhunia AK, Barodka VM, Gazi FK, Barrow RK, Wang R, Amzel LM, Berkowitz DE, Snyder SH (2011) Hydrogen sulfide as endothelium-derived hyperpolarizing factor sulfhydrates potassium channels. Circ Res 109:1259–1268
Predmore BL, Julian D, Cardounel AJ (2011) Hydrogen sulfide increases nitric oxide production from endothelial cells by an akt-dependent mechanism. Front Physiol 2:104
Resnick N, Yahav H, Shay-Salit A, Shushy M, Schubert S, Zilberman LC, Wofovitz E (2003) Fluid shear stress and the vascular endothelium: for better and for worse. Prog Biophys Mol Biol 81:177–199
Rieder MJ, Carmona R, Krieger JE, Pritchard KA Jr, Greene AS (1997) Suppression of angiotensin-converting enzyme expression and activity by shear stress. Circ Res 80:312–319
Shibata K, Miyazaki T, Ohata H, Honda K (2011) Shear stress-dependent effects of lysophosphatidic acid on agonist-induced vasomotor responses in rat mesenteric artery. J Cardiovasc Pharmacol 57:604–610
Shibuya N, Mikami Y, Kimura Y, Nagahara N, Kimura H (2009) Vascular endothelium expresses 3-mercaptopyruvate sulfurtransferase and produces hydrogen sulfide. J Biochem 146:623–626
Tang G, Wu L, Liang W, Wang R (2005) Direct stimulation of K(ATP) channels by exogenous and endogenous hydrogen sulfide in vascular smooth muscle cells. Mol Pharmacol 68:1757–1764
Tang G, Yang G, Jiang B, Ju Y, Wu L, Wang R (2013) HS is an endothelium-derived hyperpolarizing factor. Antioxid Redox Signal
Thorup C, Jones CL, Gross SS, Moore LC, Goligorsky MS (1999) Carbon monoxide induces vasodilation and nitric oxide release but suppresses endothelial NOS. Am J Physiol 277:F882–F889
Wagner CT, Durante W, Christodoulides N, Hellums JD, Schafer AI (1997) Hemodynamic forces induce the expression of heme oxygenase in cultured vascular smooth muscle cells. J Clin Invest 100:589–596
Wang R (2003) The gasotransmitter role of hydrogen sulfide. Antioxid Redox Signal 5:493–501
Wang R (2012) Physiological implications of hydrogen sulfide: a whiff exploration that blossomed. Physiol Rev 92:791–896
Wang RX, Chai Q, Lu T, Lee HC (2011) Activation of vascular BK channels by docosahexaenoic acid is dependent on cytochrome P450 epoxygenase activity. Cardiovasc Res 90:344–352
Wang XL, Ye D, Peterson TE, Cao S, Shah VH, Katusic ZS, Sieck GC, Lee HC (2005) Caveolae targeting and regulation of large conductance Ca(2+)-activated K+ channels in vascular endothelial cells. J Biol Chem 280:11656–11664
Yang G, Wu L, Jiang B, Yang W, Qi J, Cao K, Meng Q, Mustafa AK, Mu W, Zhang S, Snyder SH, Wang R (2008) H2S as a physiologic vasorelaxant: hypertension in mice with deletion of cystathionine gamma-lyase. Science 322:587–590
Ye D, Zhang D, Oltman C, Dellsperger K, Lee HC, VanRollins M (2002) Cytochrome p-450 epoxygenase metabolites of docosahexaenoate potently dilate coronary arterioles by activating large-conductance calcium-activated potassium channels. J Pharmacol Exp Ther 303:768–776
Zhao W, Zhang J, Lu Y, Wang R (2001) The vasorelaxant effect of H(2)S as a novel endogenous gaseous K(ATP) channel opener. EMBO J 20:6008–6016
Zhou W, Wang XL, Lamping KG, Lee HC (2006) Inhibition of protein kinase Cbeta protects against diabetes-induced impairment in arachidonic acid dilation of small coronary arteries. J Pharmacol Exp Ther 319:199–207
Acknowledgements
This work was supported by the National Institute of Health (HL080118, HL074180), and by the American Diabetes Association (ADA-JFA-07-39 and 1-12-BS-119). Address Correspondence to: Hon-Chi Lee, M.D., Ph.D. Email lee.honchi@mayo.edu or Qiang Chai Ph.D. Email qiang.chai@hotmail.com
Conflict of interest
All authors disclosed that they do not have any potential conflict of interest.
Author information
Authors and Affiliations
Corresponding authors
Rights and permissions
About this article
Cite this article
Chai, Q., Lu, T., Wang, XL. et al. Hydrogen sulfide impairs shear stress-induced vasodilation in mouse coronary arteries. Pflugers Arch - Eur J Physiol 467, 329–340 (2015). https://doi.org/10.1007/s00424-014-1526-y
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00424-014-1526-y