© 1997 by European Society of Cardiology
Copyright © 1997, European Society of Cardiology
Indomethacin enhances endothelial NO release — evidence for a role of PGI2 in the autocrine control of calcium-dependent autacoid production
Institute of Physiology and Pathophysiology, Johannes-Gutenberg-University Mainz, Duesbergweg 6, D-55099 Mainz, Germany
* Corresponding author. Tel. (+49-6131) 395212; Fax (+49-6131) 395644; E-mail: bolz@mzdmza.zdv.uni-mainz.de
Objective: We studied whether NO or prostacyclin (PGI2), which are continuously released by endothelial cells, have autocrine/paracrine effects on the calcium-dependent autacoid production by modulating the intracellular Ca2+ concentration ([Ca2+]i). Methods: Histamine(His)-induced [Ca2+]i increases (Fura 2-method) and NO-dependent cGMP increase were measured in human umbilical vein endothelial cells (HUVECs) before and after cyclooxygenase inhibition or application of cAMP- and cGMP-elevating drugs. Results: 0.3 µM His increased endothelial [Ca2+]i from 77±2 nM to 418±59 nM. The His-induced [Ca2+]i increases were significantly attenuated following treatment with PGI2 (by 23%) and forskolin (by 33%), both increasing the cAMP release from HUVECs (by 49% and 66%). The His-induced [Ca2+]i increases were inhibited by the protein kinase A-activator cBIMPS (by 61%) which also abolished the His-induced PGI2 release. Conversely, inhibition of the PGI2 production with indomethacin significantly augmented the His-induced [Ca2+]i increases (by 32%), resulting in a significantly augmented NO production as indicated by an enhanced LNNA-sensitive cGMP increase in HUVECs. In contrast, neither increases of cGMP (basal 0.4±0.1 pmol/mg) elicited by 10 µM SNP (21±2 pmol/mg) or 10 µM C-type natriuretic peptide (CNP, 4.6±1.6 pmol/mg) nor its reduction by 30 µM LNNA had any effect on the His-induced [Ca2+]i increases. Conclusion: PGI2 attenuates agonist-induced [Ca2+]i increases by a cAMP-dependent mechanism, thereby modulating not only its own synthesis via a negative feedback but also that of NO. Consequently, reduced PGI2 levels result in an increased NO production. NO which does not cause a negative feedback control by cGMP might therefore compensate for the lack of PGI2.
KEYWORDS HUVECs; Histamine; cAMP; cGMP; Feedback
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  Z. F. Ba and I. H. Chaudry Role of estrogen receptor subtypes in estrogen-induced organ-specific vasorelaxation after trauma-hemorrhage Am J Physiol Heart Circ Physiol, November 1, 2008; 295(5): H2061 - H2067. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Hirao, K. Kondo, K. Takeuchi, N. Inui, K. Umemura, K. Ohashi, and H. Watanabe Cyclooxygenase-dependent vasoconstricting factor(s) in remodelled rat femoral arteries Cardiovasc Res, July 1, 2008; 79(1): 161 - 168. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Ide, M. Worthley, T. Anderson, and M. J. Poulin Effects of the nitric oxide synthase inhibitor L-NMMA on cerebrovascular and cardiovascular responses to hypoxia and hypercapnia in humans J. Physiol., October 1, 2007; 584(1): 321 - 332. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. F. Ba, A. Lu, T. Shimizu, L. Szalay, M. G. Schwacha, L. W. Rue III, K. I. Bland, and I. H. Chaudry 17beta-Estradiol modulates vasoconstriction induced by endothelin-1 following trauma-hemorrhage Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H245 - H250. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. D. Shipley, S. J. Kim, and J. M. Muller-Delp Time course of flow-induced vasodilation in skeletal muscle: contributions of dilator and constrictor mechanisms Am J Physiol Heart Circ Physiol, April 1, 2005; 288(4): H1499 - H1507. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Golay, C. Haeberli, A. Delachaux, L. Liaudet, P. Kucera, B. Waeber, and F. Feihl Local heating of human skin causes hyperemia without mediation by muscarinic cholinergic receptors or prostanoids J Appl Physiol, November 1, 2004; 97(5): 1781 - 1786. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. S. Clifford and Y. Hellsten Vasodilatory mechanisms in contracting skeletal muscle J Appl Physiol, July 1, 2004; 97(1): 393 - 403. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Wang, R. S. Al-Lamki, H. Zhang, N. Kirkiles-Smith, M. L. Gaeta, S. Thiru, J. S. Pober, and J. R. Bradley Histamine Antagonizes Tumor Necrosis Factor (TNF) Signaling by Stimulating TNF Receptor Shedding from the Cell Surface and Golgi Storage Pool J. Biol. Chem., June 6, 2003; 278(24): 21751 - 21760. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. McAllister Endothelium-dependent vasodilation in different rat hindlimb skeletal muscles J Appl Physiol, May 1, 2003; 94(5): 1777 - 1784. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Fuloria, T. K. Smith, and J. L. Aschner Role of 5,6-epoxyeicosatrienoic acid in the regulation of newborn piglet pulmonary vascular tone Am J Physiol Lung Cell Mol Physiol, August 1, 2002; 283(2): L383 - L389. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. N Dedkova and L. A Blatter Nitric oxide inhibits capacitative Ca2+ entry and enhances endoplasmic reticulum Ca2+ uptake in bovine vascular endothelial cells J. Physiol., February 15, 2002; 539(1): 77 - 91. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. P. Marrelli Mechanisms of endothelial P2Y1- and P2Y2-mediated vasodilatation involve differential [Ca2+]i responses Am J Physiol Heart Circ Physiol, October 1, 2001; 281(4): H1759 - H1766. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Campos-Toimil, C. Lugnier, M.-T. Droy-Lefaix, and K. Takeda Inhibition of Type 4 Phosphodiesterase by Rolipram and Ginkgo biloba Extract (EGb 761) Decreases Agonist-Induced Rises in Internal Calcium in Human Endothelial Cells Arterioscler Thromb Vasc Biol, September 1, 2000; 20 (9): e34 - e40. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-S. Bolz, S. Pieperhoff, C. De Wit, and U. Pohl Intact endothelial and smooth muscle function in small resistance arteries after 48 h in vessel culture Am J Physiol Heart Circ Physiol, September 1, 2000; 279(3): H1434 - H1439. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. H. Awtry and J. Loscalzo Aspirin Circulation, March 14, 2000; 101(10): 1206 - 1218. [Full Text] [PDF]
|
|
|
|
 |
|
 S.-S. BOLZ, B. FISSLTHALER, S. PIEPERHOFF, C. DE WIT, I. FLEMING, R. BUSSE, and U. POHL Antisense oligonucleotides against cytochrome P450 2C8 attenuate EDHF-mediated Ca2+ changes and dilation in isolated resistance arteries FASEB J, February 1, 2000; 14(2): 255 - 260. [Abstract] [Full Text]
|
|