Influence of celecoxib on the vasodilating properties of human mesenteric arteries constricted with endothelin-1

Grześk,Grzegorz; Szadujkis-Szadurska,Katarzyna; Matusiak,Grzegorz; Malinowski,Bartosz; Gajdus,Marta; Wiciński,Michał; Szadujkis-Szadurski,Leszek

doi:10.3892/br.2014.233

Influence of celecoxib on the vasodilating properties of human mesenteric arteries constricted with endothelin-1

Authors:
- Grzegorz Grześk
- Katarzyna Szadujkis-Szadurska
- Grzegorz Matusiak
- Bartosz Malinowski
- Marta Gajdus
- Michał Wiciński
- Leszek Szadujkis-Szadurski
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Affiliations: Department of Pharmacology and Therapeutics, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz 85-094, Poland
Published online on: January 29, 2014 https://doi.org/10.3892/br.2014.233
Pages: 412-418

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Abstract

The mitogenic and vasoconstrictive properties of the vascular system are attributed to endothelin‑1 (ET‑1). ET-1 serum concentration increases in a number of pathological conditions, particularly in those associated with blood vessel constriction. ET‑1 is also associated with the underlying pathomechanisms of primary pulmonary hypertension, arterial hypertension and eclampsia. The aim of this study was to compare the vasodilating properties of selected phosphodiesterase (PDE) inhibitors and celecoxib in human mesenteric arteries constricted with ET‑1, and investigate the role of the endothelium in relaxation. Perfused human mesenteric arteries were collected and stored under the same conditions as organs for transplantation. The mesenteric arteries (with and without the endothelium) were constricted by the addition of ET‑1 and treated with one of the following: sildenafil (PDE5 inhibitor), zaprinast (PDE5 and 6 inhibitor), rolipram (PDE4 inhibitor) and celecoxib [cyclooxygenase‑2 (COX‑2) inhibitor]. Based on the observed changes of the perfusion pressure, concentration response curves (CRCs) were prepared for the respective inhibitors and the EC50 (concentration causing an effect equal to half of the maximum effect), pD2 (negative common logarithm of EC50) and relative potency (RP) were calculated. The results suggested that all the inhibitors triggered a concentration‑dependent decrease in the perfusion pressure in isolated human superior mesenteric arteries with endothelium constricted by the addition of ET‑1. In the arteries without endothelium, CRCs for celecoxib and rolipram were shifted to the right without a significant decrease in the maximum dilating effect. Moreover, CRCs for sildenafil and zaprinast were shifted to the right with a simultaneous significant decrease in the maximum dilating effect and with an increased inclination angle in reference to the concentration axis. In the presence of the endothelium, all of the evaluated PDE inhibitors, as well as celecoxib, reduced the reactivity of the mesenteric arteries caused by ET‑1. Sildenafil indicated the lowest efficacy in the presence of the endothelium, but showed a higher potency compared to that of the other compounds. Removing the endothelium significantly reduced the vasodilating efficacy of PDE5 and 6 inhibitors and a statistically significant influence on the vasodilating efficacy of PDE4 inhibitor and celecoxib was observed. The high vasorelaxing efficacy of celecoxib at the background of the PDE inhibitors was observed, not only in the presence, but also in the absence of the endothelium and may be evidence for the relaxation induced by this COX‑2 inhibitor in the cAMP‑ and cGMP‑dependent pathways.

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1	Grześk G, Koziński M, Navarese EP, Krzyżanowski M, Grześk E, Kubica A, Siller-Matula JM, Castriota F and Kubica J: Ticagrelor, but not clopidogrel and prasugrel, prevents ADP-induced vascular smooth muscle cell contraction: a placebo-controlled study in rats. Thrombos Res. 130:65–69. 2012.PubMed/NCBI
2	Rajakariar R, Yaqoob MM and Gilroy WD: COX-2 in inflammation and resolution. Mol Interv. 6:199–207. 2006. View Article : Google Scholar : PubMed/NCBI
3	Smyth EM and FitzGerald GA: Prostaglandin mediators. Handbook of Cell Signaling. Bradshaw RA and Dennis EA: Second Edition. Academic Press; San Diego: pp. 265–273. 2003, View Article : Google Scholar
4	Bresalier RS, Sandler RS, Quan H, Bolognese JA, Oxenius B, Horgan K, Lines C, Riddell R, Morton D, Lanas A, Konstam MA and Baron JA: Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. N Engl J Med. 352:1092–1102. 2005. View Article : Google Scholar : PubMed/NCBI
5	FitzGerald GA: Coxibs and cardiovascular disease. N Engl J Med. 351:1709–1711. 2004. View Article : Google Scholar : PubMed/NCBI
6	Nussmeier NA, Whelton AA and Brown NT: Complications of the COX-2 inhibitors parecoxib and waldecoxib after cardiac surgery. N Engl J Med. 352:1081–1091. 2005. View Article : Google Scholar : PubMed/NCBI
7	Solomon SD, McMurray JJV, Pfeffer MA, Wittes J, Fowler R, Finn P, Anderson WF, Zauber A, Hawk E and Bertagnolli M; Adenoma prevention with celecoxib (APC) study investigators. Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N Engl J Med. 352:1071–1080. 2005. View Article : Google Scholar : PubMed/NCBI
8	Bavry AA, Khaliq A, Gong Y, Handberg EM, Cooper-Dehoff RM and Pepine CJ: Harmful effects of NSAIDs among patients with hypertension and coronary artery disease. Am J Med. 124:614–620. 2011. View Article : Google Scholar : PubMed/NCBI
9	Bertagnolli MM, Hsu M, Hawk ET, Eagle CJ and Zauber AG: Statin use and colorectal adenoma risk: results from the adenoma prevention with celecoxib trial. Cancer Prev Res. 3:588–596. 2010. View Article : Google Scholar : PubMed/NCBI
10	Koller A, Sun D, Huang A and Kaley G: Corelease of nitric oxide and prostaglandins mediates flow-dependent dilation of rat gracilis muscle arterioles. Am J Physiol. 267:H326–H332. 1994.PubMed/NCBI
11	Ganesan AN, Maack C, Johns DC, Sidor A and O’Rourke B: Beta-adrenergic stimulation of L-type Ca²⁺channels in cardiac myocytes requires the distal carboxyl terminus of α_1Cbut not serine 1928. Circ Res. 98:e11–e18. 2006.PubMed/NCBI
12	Keef KD, Hume JR and Zhong J: Regulation of cardiac and smooth muscle Ca²⁺channels (CaV1.2a,b) by protein kinases. Am J Physiol Cell Physiol. 281:C1743–C1756. 2001.PubMed/NCBI
13	Kilic A, Bubikat A, Gassner B, Baba HA and Kuhn M: Local actions of atrial natriuretic peptide counteract angiotensin II stimulated cardiac remodeling. Endocrinology. 148:4162–4169. 2007. View Article : Google Scholar : PubMed/NCBI
14	Münzel T, Feil R, Mülsch A, Lohmann SM, Hofmann F and Walter U: Physiology and pathophysiology of vascular signaling controlled by cyclic guanosine 3′,5′-cyclic monophosphate-dependent protein kinase. Circulation. 108:2172–2183. 2003.
15	Rybalkin SD, Yan C, Bornfeldt KE and Beavo JA: Cyclic GMP phosphodiesterases and regulation of smooth muscle function. Circ Res. 93:280–291. 2003. View Article : Google Scholar : PubMed/NCBI
16	Zaccolo M and Movsesian MA: cAMP and cGMP signaling cross-talk: role of phosphodiesterases and implications for cardiac pathophysiology. Circ Res. 100:1569–1578. 2007. View Article : Google Scholar : PubMed/NCBI
17	Bender AT and Beavo JA: Cyclic nucleotide phosphodiesterases: molecular regulation to clinical use. Pharmacol Rev. 58:488–520. 2006. View Article : Google Scholar : PubMed/NCBI
18	Somlyo AP and Somlyo AV: Ca²⁺sensitivity of smooth muscle and nonmuscle myosin II: modulated by G proteins, kinases, and myosin phosphatase. Physiol Rev. 83:1325–1358. 2003.
19	Oberwittler H, Hirschfeld-Warneken A, Wesch R, Willerich H, Teichert L, Heinz KH, Lehr E, Ding R, Haefeli WE and Mikus G: Significant pharmacokinetic and pharmacodynamic interaction of warfarin with the NO-independent sGC activator HMR1766. J Clin Pharmacol. 47:70–77. 2007. View Article : Google Scholar : PubMed/NCBI
20	Yetik-Anacak G, Xia T, Dimitropoulou C, Venema RC and Catravas JD: Effects of hsp90 binding inhibitors on sGC-mediated vascular relaxation. Am J Physiol Heart Circ Physiol. 291:H260–H268. 2006. View Article : Google Scholar : PubMed/NCBI
21	Herrera M and Garvin JL: Novel role of AQP-1 in NO-dependent vasorelaxation. Am J Physiol Renal Physiol. 292:F1443–F1451. 2007. View Article : Google Scholar : PubMed/NCBI
22	Tanaka K and Koyama Y: Endothelins decrease the expression of aquaporins and plasma membrane water permeability in cultured rat astrocytes. J Neurosci Res. 89:320–328. 2011. View Article : Google Scholar : PubMed/NCBI
23	Slupski M, Szadujkis-Szadurski L, Grzesk G, Szadujkis-Szadurski R, Szadujkis-Szadurska K, Wlodarczyk Z, Masztalerz M, Piotrowiak I and Jasiński M: Guanylate cyclase activators influence reactivity of human mesenteric superior arteries retrieved and preserved in the same conditions as transplanted kidneys. Transplant Proc. 39:1350–1353. 2007. View Article : Google Scholar
24	Chenevard R, Hurlimann D, Bechir M, Enseleit F, Spieker L, Hermann M and Riesen W: Selective COX-2 inhibition improves endothelial function in coronary artery disease. Circulation. 107:405–409. 2003. View Article : Google Scholar : PubMed/NCBI
25	Simionescu M: Implications of early structural-functional changes in the endothelium for vascular disease. Arterioscler Thromb Vasc Biol. 27:266–274. 2007. View Article : Google Scholar : PubMed/NCBI
26	Foudi N, Kotelevets L, Louedec L, Leseche G, Henin D, Chastre E and Norel X: Vasorelaxation induced by prostaglandin E(2) in human pulmonary vein: role of the EP(4) receptor subtype. Br J Pharmacol. 154:1631–1639. 2008. View Article : Google Scholar : PubMed/NCBI
27	Grosser T, Fries S and FitzGerald GA: Biological basis for the cardiovascular consequences of COX-2 inhibition: therapeutic challenges and opportunities. J Clin Invest. 116:4–15. 2006. View Article : Google Scholar : PubMed/NCBI
28	Mamdani M, Juurlink DN, Lee DS, Rochon PA, Kopp A, Naglie G, Austin PC, Laupacis A and Stukel TA: Cyclooxygenase-2 inhibitors versus non-selective non-steroidal anti-inflammatory drugs and congestive heart failure outcomes in elderly patients: a population-based cohort study. Lancet. 363:1751–1756. 2004. View Article : Google Scholar : PubMed/NCBI
29	Wolfe F, Zhao S and Pettitt D: Blood pressure destabilization and edema among 8538 users of celecoxib, rofecoxib, and nonselective nonsteroidal antiinflammatory drugs (NSAID) and nonusers of NSAID receiving ordinary clinical care. J Rheumatol. 31:1143–1151. 2004.
30	Aw TJ, Haas SJ, Liew D and Krum H: Meta-analysis of cyclooxygenase-2 inhibitors and their effects on blood pressure. Arch Intern Med. 165:490–496. 2005. View Article : Google Scholar : PubMed/NCBI
31	Brinker A, Goldkind L, Bonnel R and Beitz J: Spontaneous reports of hypertension leading to hospitalisation in association with rofecoxib, celecoxib, nabumetone and oxaprozin. Drugs Aging. 21:479–484. 2004. View Article : Google Scholar : PubMed/NCBI
32	Cheng Y, Austin SC, Rocca B, Koller BH, Coffman TM, Grosser T, Lawson JA and FitzGerald GA: Role of prostacyclin in the cardiovascular response to thromboxane A2. Science. 296:539–541. 2002. View Article : Google Scholar : PubMed/NCBI
33	Klein T, Eltze M, Grebe T, Hatzelmann A and Kömhoff M: Celecoxib dilates guinea-pig coronaries and rat aortic rings and amplifies NO/cGMP signaling by PDE5 inhibition. Cardiovasc Res. 75:390–397. 2007. View Article : Google Scholar : PubMed/NCBI
34	Francois H, Athirakul K, Howell D, Dash R, Mao L, Kim HS, Rockman HA, Fitzgerald GA, Koller BH and Coffman TM: Prostacyclin protects against elevated blood pressure and cardiac fibrosis. Cell Metab. 2:201–207. 2005. View Article : Google Scholar : PubMed/NCBI
35	Gudbjornsson B, Thorsteinsson SB, Sigvaldason H, Einarsdottir R, Johannsson M, Zoega H, Halldorsson M and Thorgeirsson G: Rofecoxib, but not celecoxib, increases the risk of thromboembolic cardiovascular events in young adults - a nationwide registry-based study. Eur J Clin Pharmacol. 66:619–625. 2010. View Article : Google Scholar : PubMed/NCBI
36	Akiko H, Kazunao K, Kazuhiko T, Naoki I, Kazuo U, Kyoichi O and Hiroshi W: Cyclooxygenase-dependent vasoconstricting factor(s) in remodelled rat femoral arteries. Cardiovasc Res. 79:161–168. 2008. View Article : Google Scholar : PubMed/NCBI
37	Flórez A, de Haro J, Martínez E, Varela C, Bleda S and Acín F: Selective cyclooxygenase-2 inhibition reduces endothelial dysfunction and improves inflammatory status in patients with intermittent claudication. Rev Esp Cardiol. 62:851–857. 2009.PubMed/NCBI
38	Widlansky ME, Price DT, Gokce N, Eberhardt RT, Duffy SJ, Holbrook M, Maxwell C, Palmisano J, Keaney JF Jr, Morrow JD and Vita JA: Short- and long-term COX-2 inhibition reverses endothelial dysfunction in patients with hypertension. Hypertension. 42:310–315. 2003. View Article : Google Scholar : PubMed/NCBI
39	Foudi N, Norel X, Rienzo M, Louedec L, Brink C, Michel JB and Back M: Altered reactivity to norepinephrine through COX-2 induction by vascular injury in hypercholesterolemic rabbits. Am J Physiol Heart Circ Physiol. 297:H1882–H1888. 2009. View Article : Google Scholar : PubMed/NCBI