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Current Molecular Pharmacology


ISSN (Print): 1874-4672
ISSN (Online): 1874-4702

Research Article

Vasorelaxant Effect of Novel Nitric Oxide-Hydrogen Sulfide Donor Chalcone in Isolated Rat Aorta: Involvement of cGMP Mediated sGC and Potassium Channel Activation

Author(s): Amol Sherikar*, Rakesh Dhavale and Manish Bhatia

Volume 13 , Issue 2 , 2020

Page: [126 - 136] Pages: 11

DOI: 10.2174/1874467212666191025092346

Price: $65


Background and Objective: Recently, nitric oxide (NO) and hydrogen sulfide (H2S) donating moieties were extensively studied for their role in the vasculature as they are responsible for many cellular and pathophysiological functioning. The objective of the present study is to evaluate novel NO and H2S donating chalcone moieties on isolated rat aorta for vasorelaxation, and to investigate the probable mechanism of action.

Methods: To extend our knowledge of vasorelaxation by NO and H2S donor drugs, here we investigated the vasorelaxing activity of novel NO and H2S donating chalcone moieties on isolated rat aorta. The mechanism of vasorelaxation by these molecules was investigated by performing in vitro cGMP mediated sGC activation assay and using Tetraethylammonium chloride (TEA) as a potassium channel blocker and Methylene blue as NO blocker.

Results: Both NO and H2S donating chalcone moieties were found to be potent vasorelaxant. The compound G4 and G5 produce the highest vasorelaxation with 3.716 and 3.789 M of pEC50, respectively. After the addition of TEA, G4 and G5 showed 2.772 and 2.796 M of pEC50, respectively. The compounds Ca1, Ca2, and D7 produced significant activation and release of cGMP mediated sGC which was 1.677, 1.769 and 1.768 M of pEC50, respectively.

Conclusion: The vasorelaxation by NO-donating chalcones was blocked by Methylene blue but it did not show any effect on H2S donating chalcones. The vasorelaxing potency of NO-donating molecules was observed to be less affected by the addition of TEA but H2S donors showed a decrease in both efficacy and potency. The cGMP release was more in the case of NO-donating molecules. The tested compounds were found potent for relaxing vasculature of rat aorta.

Keywords: Vasorelaxation, nitric oxide, hydrogen sulfide, tetraethylammonium chloride (TEA), in-vitro, cGMP mediated sGC.

Graphical Abstract
Bhatia, M. Hydrogen sulfide as a vasodilator. IUBMB Life, 2005, 57(9), 603-606.
[] [PMID: 16203678]
Sherikar, A.S.; Bhatia, M.S.; Dhavale, R.P.; Bhatia, N.M.; Choudhari, P.B. Nitric Oxide (NO) and Hydrogen Sulfide (H2S): Molecular Targets for Vascular Muscle Relaxation. Curr. Trends Biotechnol. Pharm., 2015, 9(4), 411-419.
Folasire, O.; Mills, K.A.; Sellers, D.J.; Chess-Williams, R. Three Gaseous Neurotransmitters, Nitric oxide, Carbon Monoxide, and Hydrogen Sulfide, Are Involved in the Neurogenic Relaxation Responses of the Porcine Internal Anal Sphincter. J. Neurogastroenterol. Motil., 2016, 22(1), 141-148.
[] [PMID: 26486177]
Elliott, S.N.; McKnight, W.; Cirino, G.; Wallace, J.L. A nitric oxide-releasing nonsteroidal anti-inflammatory drug accelerates gastric ulcer healing in rats. Gastroenterology, 1995, 109(2), 524-530.
[] [PMID: 7615202]
Del Soldato, P.; Cuzzolin, L.; Adami, A.; Conforiti, A.; Crivellente, F.; Benoni, G. Nitric oxide releasing NSAIDs, a novel class of safe and effective anti-inflammatory agents. Inflammopharmacology, 1996, 4(2), 181-188.
Wallace, J.L.; Reuter, B.; Cicala, C.; McKnight, W.; Grisham, M.B.; Cirino, G. Novel nonsteroidal anti-inflammatory drug derivatives with markedly reduced ulcerogenic properties in the rat. Gastroenterology, 1994, 107(1), 173-179.
[] [PMID: 8020659]
Fiorucci, S.; Distrutti, E.; Cirino, G.; Wallace, J.L. The emerging roles of hydrogen sulfide in the gastrointestinal tract and liver. Gastroenterology, 2006, 131(1), 259-271.
[] [PMID: 16831608]
Wang, R. Two’s company, three’s a crowd: can H2S be the third endogenous gaseous transmitter? FASEB J., 2002, 16(13), 1792-1798.
[] [PMID: 12409322]
Goubern, M.; Andriamihaja, M.; Nübel, T.; Blachier, F.; Bouillaud, F. Sulfide, the first inorganic substrate for human cells. FASEB J., 2007, 21(8), 1699-1706.
[] [PMID: 17314140]
Distrutti, E.; Sediari, L.; Mencarelli, A.; Renga, B.; Orlandi, S.; Russo, G.; Caliendo, G.; Santagada, V.; Cirino, G.; Wallace, J.L.; Fiorucci, S. 5-Amino-2-hydroxybenzoic acid 4-(5-thioxo-5H-[1,2]dithiol-3yl)-phenyl ester (ATB-429), a hydrogen sulfide-releasing derivative of mesalamine, exerts antinociceptive effects in a model of postinflammatory hypersensitivity. J. Pharmacol. Exp. Ther., 2006, 319(1), 447-458.
[] [PMID: 16855178]
Zanardo, R.C.; Brancaleone, V.; Distrutti, E.; Fiorucci, S.; Cirino, G.; Wallace, J.L. Hydrogen sulfide is an endogenous modulator of leukocyte-mediated inflammation. FASEB J., 2006, 20(12), 2118-2120.
[] [PMID: 16912151]
Burgaud, J.L.; Ongini, E.; Del Soldato, P. Nitric oxide-releasing drugs: a novel class of effective and safe therapeutic agents. Ann. N. Y. Acad. Sci., 2002, 962, 360-371.
[] [PMID: 12076987]
Cirino, G. Nitric oxide releasing drugs: from bench to bedside. Dig. Liver Dis., 2003, 35(Suppl. 2), S2-S8.
[] [PMID: 12846438]
Keeble, J.E.; Moore, P.K. Pharmacology and potential therapeutic applications of nitric oxide-releasing non-steroidal anti-inflammatory and related nitric oxide-donating drugs. Br. J. Pharmacol., 2002, 137(3), 295-310.
[] [PMID: 12237248]
Lopez-Belmonte, J.; Whittle, B.J.R.; Moncada, S. The actions of nitric oxide donors in the prevention or induction of injury to the rat gastric mucosa. Br. J. Pharmacol., 1993, 108(1), 73-78.
[] [PMID: 8428217]
Fiorucci, S.; Santucci, L.; Gresele, P.; Faccino, R.M.; Del Soldato, P.; Morelli, A. Gastrointestinal safety of NO-aspirin (NCX-4016) in healthy human volunteers: a proof of concept endoscopic study. Gastroenterology, 2003, 124(3), 600-607.
[] [PMID: 12612897]
Bian, J.S.; Yong, Q.C.; Pan, T.T.; Feng, Z.N.; Ali, M.Y.; Zhou, S.; Moore, P.K. Role of hydrogen sulfide in the cardioprotection caused by ischemic preconditioning in the rat heart and cardiac myocytes. J. Pharmacol. Exp. Ther., 2006, 316(2), 670-678.
[] [PMID: 16204473]
Su, Y.W.; Liang, C.; Jin, H.F.; Tang, X.Y.; Han, W.; Chai, L.J.; Zhang, C.Y.; Geng, B.; Tang, C.S.; Du, J.B. Hydrogen sulfide regulates cardiac function and structure in adriamycin-induced cardiomyopathy. Circ. J., 2009, 73(4), 741-749.
[] [PMID: 19246810]
Elrod, J.W.; Calvert, J.W.; Morrison, J.; Doeller, J.E.; Kraus, D.W.; Tao, L.; Jiao, X.; Scalia, R.; Kiss, L.; Szabo, C.; Kimura, H.; Chow, C.W.; Lefer, D.J. Hydrogen sulfide attenuates myocardial ischemia-reperfusion injury by preservation of mitochondrial function. Proc. Natl. Acad. Sci. USA, 2007, 104(39), 15560-15565.
[] [PMID: 17878306]
Martellia, A.; Testai, L.; Breschi, M.C.; Lawson, K.; McKay, N.G.; Miceli, F.; Taglialatela, M.; Calderone, V. Vasorelaxation by hydrogen sulfide involves activation of Kv7 potassium channels. Pharm. Res., 2013, 70(1), 27-34.
Cary, S.P.; Winger, J.A.; Marletta, M.A. Tonic and acute nitric oxide signaling through soluble guanylate cyclase is mediated by nonheme nitric oxide, ATP, and GTP. Proc. Natl. Acad. Sci. USA, 2005, 102(37), 13064-13069.
[] [PMID: 16131543]
Zaragoza, C.; Soria, E.; López, E.; Browning, D.; Balbín, M.; López-Otín, C.; Lamas, S. Activation of the mitogen activated protein kinase extracellular signal-regulated kinase 1 and 2 by the nitric oxide-cGMP-cGMP-dependent protein kinase axis regulates the expression of matrix metalloproteinase 13 in vascular endothelial cells. Mol. Pharmacol., 2002, 62(4), 927-935.
[] [PMID: 12237340]
Zhang, M.; Koitabashi, N.; Nagayama, T.; Rambaran, R.; Feng, N.; Takimoto, E.; Koenke, T.; O’Rourke, B.; Champion, H.C.; Crow, M.T.; Kass, D.A. Expression, activity, and pro-hypertrophic effects of PDE5A in cardiac myocytes. Cell. Signal., 2008, 20(12), 2231-2236.
[] [PMID: 18790048]
Zhang, Q.; Moalem, J.; Tse, J.; Scholz, P.M.; Weiss, H.R. Effects of natriuretic peptides on ventricular myocyte contraction and role of cyclic GMP signaling. Eur. J. Pharmacol., 2005, 510(3), 209-215.
[] [PMID: 15763244]
Surks, H.K. cGMP-dependent protein kinase I and smooth muscle relaxation: a tale of two isoforms. Circ. Res., 2007, 101(11), 1078-1080.
[] [PMID: 18040024]
Spinelli, V.; Vona, A.; Corti, F.; Diolaiuti, L.; Zanardelli, M.; Sartiani, L.; Failli, P. Role of Nitric Oxide, Nitric Oxide Synthase, Soluble Guanylyl Cyclase, and cGMP-Dependent Protein Kinase I in Mouse Stem Cell Cardiac Development. Stem Cells Int., 2016, 2016 2868323
[] [PMID: 27840646]
Archer, S.L.; Huang, J.M.; Hampl, V.; Nelson, D.P.; Shultz, P.J.; Weir, E.K. Nitric oxide and cGMP cause vasorelaxation by activation of a charybdotoxin-sensitive K channel by cGMP-dependent protein kinase. Proc. Natl. Acad. Sci. USA, 1994, 91(16), 7583-7587.
[] [PMID: 7519783]
Artim, D.E.; Kullmann, F.A.; Daugherty, S.L.; Wu, H.Y.; de Groat, W.C. Activation of the nitric oxide-cGMP pathway reduces phasic contractions in neonatal rat bladder strips via protein kinase G. Am. J. Physiol. Renal Physiol., 2009, 297(2), F333-F340.
[] [PMID: 19493964]
Mayer, B.; Pfeiffer, S.; Schrammel, A.; Koesling, D.; Schmidt, K.; Brunner, F. A new pathway of nitric oxide/cyclic GMP signaling involving S-nitrosoglutathione. J. Biol. Chem., 1998, 273(6), 3264-3270.
[] [PMID: 9452441]
Miller, M.R.; Megson, I.L. Recent developments in nitric oxide donor drugs. Br. J. Pharmacol., 2007, 151(3), 305-321.
[] [PMID: 17401442]
Knowles, R.G.; Moncada, S. Nitric oxide synthases in mammals. Biochem. J., 1994, 298(Pt 2), 249-258.
[] [PMID: 7510950]
Vankelecom, H.; Matthys, P.; Denef, C. Inducible nitric oxide synthase in the anterior pituitary gland: induction by interferon-gamma in a subpopulation of folliculostellate cells and in an unidentifiable population of non-hormone-secreting cells. J. Histochem. Cytochem., 1997, 45(6), 847-857.
[] [PMID: 9199670]
Duvilanski, B.H.; Zambruno, C.; Seilicovich, A.; Pisera, D.; Lasaga, M.; Diaz, M.C.; Belova, N.; Rettori, V.; McCann, S.M. Role of nitric oxide in control of prolactin release by the adenohypophysis. Proc. Natl. Acad. Sci. USA, 1995, 92(1), 170-174.
[] [PMID: 7529411]
Ding, Y.; Vaziri, N.D. Calcium channel blockade enhances nitric oxide synthase expression by cultured endothelial cells. Hypertension, 1998, 32(4), 718-723.
[] [PMID: 9774369]
Ragy, M.; Elbassuoni, E. The role of nitric oxide and L-type calcium channel blocker in the contractility of rabbit ileum in vitro. J. Physiol. Biochem., 2012, 68(4), 521-528.
[] [PMID: 22528554]
Rahimi, R.; Ghiasi, S.; Azimi, H.; Fakhari, S.; Abdollahi, M. A review of the herbal phosphodiesterase inhibitors; future perspective of new drugs. Cytokine, 2010, 49(2), 123-129.
[] [PMID: 20005737]
Godfraind, T. Discovery and Development of Calcium Channel Blockers. Front. Pharmacol., 2017, 8, 286.
[] [PMID: 28611661]
Lawson, K. Potassium channel openers as potential therapeutic weapons in ion channel disease. Kidney Int., 2000, 57(3), 838-845.
[] [PMID: 10720937]
Edwards, G.; Weston, A.H. Potassium channel openers and vascular smooth muscle relaxation. Pharmacol. Ther., 1990, 48(2), 237-258.
[] [PMID: 2293241]
Hsieh, H.K.; Lee, T.H.; Wang, J.P.; Wang, J.J.; Lin, C.N. Synthesis and anti-inflammatory effect of chalcones and related compounds. Pharm. Res., 1998, 15(1), 39-46.
[] [PMID: 9487544]
Torigoe, T.; Arisawa, M.; Itoh, S.; Fujiu, M.; Maruyama, H.B. Anti-mutagenic chalcones: antagonizing the mutagenicity of benzo(a)pyrene on Salmonella typhimurium. Biochem. Biophys. Res. Commun., 1983, 112(3), 833-842.
[] [PMID: 6303339]
Hamdy, N.A.; Kamel, G.M. Potent anti-inflammatory and analgesic activities of new derivatives of chalcone, pyridine, pyrazole, and isoxazole incorporated into 5,6,7,8-tetrahydronaphthalene. Egypt. Pharm. J., 2012, 11(1), 22-30.
Anto, R.J.; Sukumaran, K.; Kuttan, G.; Rao, M.N.; Subbaraju, V.; Kuttan, R. Anticancer and antioxidant activity of synthetic chalcones and related compounds. Cancer Lett., 1995, 97(1), 33-37.
[] [PMID: 7585475]
Haraguchi, H.; Ishikawa, H.; Mizutani, K.; Tamura, Y.; Kinoshita, T. Antioxidative and superoxide scavenging activities of retrochalcones in Glycyrrhiza inflata. Bioorg. Med. Chem., 1998, 6(3), 339-347.
[] [PMID: 9568287]
Anto, R.J.; Kuttan, G.; Kuttan, R.; Sathyanarayana, K.; Rao, M.N.A. Tumor-Reducing and Antioxidant Activities of Sydnone-Substituted Chalcones. J. Clin. Biochem. Nutr., 1994, 17(2), 73-80.
Wattenberg, L.W.; Coccia, J.B.; Galbraith, A.R. Inhibition of carcinogen-induced pulmonary and mammary carcinogenesis by chalcone administered subsequent to carcinogen exposure. Cancer Lett., 1994, 83(1-2), 165-169.
[] [PMID: 8062211]
De Vincenzo, R.; Ferlini, C.; Distefano, M.; Gaggini, C.; Riva, A.; Bombardelli, E.; Morazzoni, P.; Valenti, P.; Belluti, F.; Ranelletti, F.O.; Mancuso, S.; Scambia, G. In vitro evaluation of newly developed chalcone analogues in human cancer cells. Cancer Chemother. Pharmacol., 2000, 46(4), 305-312.
[] [PMID: 11052628]
Sukumaran, K.; Kuttan, R. Screening of 11 ferns for cytotoxic and antitumor potential with special reference to Pityrogramma calomelanos. J. Ethnopharmacol., 1991, 34(1), 93-96.
[] [PMID: 1753793]
Kelloff, G.J.; Boone, C.W.; Crowell, J.A.; Steele, V.E.; Lubet, R.; Sigman, C.C. Chemopreventive drug development: perspectives and progress. Cancer Epidemiol. Biomarkers Prev., 1994, 3(1), 85-98.
[PMID: 8118391]
Nam, K.Y.; Choi, N.S.; Han, C.K.; Ahn, S.K. Identification of chalcones as potent and selective PDE5A1 inhibitors. Bioorg. Med. Chem. Lett., 2012, 22(12), 3983-3987.
[] [PMID: 22607677]
Bhatia, M.S.; Sherikar, A.S.; Dhavale, R.P. Synthesis and In-vitro Phosphodiesterase 5 and 5A Inhibitory Activity of Novel 3-(3-thioxo-3h-1,2-dithiol-5-yl)phenyl4-[(1e)-3-oxo-3-phenylprop-1-en-1yl]benzoate and their Analogues. Curr. Enzym. Inhib., 2018, 14(2), 85-91.
Sherikar, A.S.; Bhatia, M.S.; Dhavale, R.P. Synthesis, Docking studies and In-vitro evaluation of novel chalcones as potent inhibitors of Phosphodiesterase 5 from human platelet and 5 A from bovine recombinant. New J. Chem., 2018, 42(17), 14365-14385.
Bhatia, M.S.; Sherikar, A.S. Investigation of Phosphodiesterase 5A (PDE5A) Inhibitors by Pharmacophore Modeling, Virtual Screening and Molecular Docking Approach J. Appl. Pharm. Sci, 2017, 7(9), 038-043.
Matsuura, M.; Kimura, Y.; Nakata, K.; Baba, K.; Okuda, H. Artery relaxation by chalcones isolated from the roots of Angelica keiskei. Planta Med., 2001, 67(3), 230-235.
[] [PMID: 11345693]
Luna-Vázquez, F.J.; Ibarra-Alvarado, C.; Rojas-Molina, A.; Rojas-Molina, I.; Zavala-Sánchez, M.A. Vasodilator compounds derived from plants and their mechanisms of action. Molecules, 2013, 18(5), 5814-5857.
[] [PMID: 23685938]
Sherman, G.P.; Packman, E.W.; Rossi, G.V. Electrolyte alterations in vascular smooth muscle and hypotensive activity of a new chalcone derivative. J. Pharm. Sci., 1968, 57(5), 733-737.
[] [PMID: 4297948]
Sherikar, A.; Dhavale, R.; Bhatia, M. Investigation of anti-inflammatory, nitric oxide donating, vasorelaxation and ulcerogenic activities of 1, 3-diphenylprop-2-en-1-one derivatives in animal models. Clin. Exp. Pharmacol. Physiol., 2019, 46(5), 483-495.
[] [PMID: 30714176]
Kodela, R.; Chattopadhyay, M.; Kashfi, K. NOSH-Aspirin: A Novel Nitric Oxide-Hydrogen Sulfide-Releasing Hybrid: A New Class of Anti-inflammatory Pharmaceuticals. ACS Med. Chem. Lett., 2012, 3(3), 257-262.
[] [PMID: 22916316]
Fiorucci, S.; Orlandi, S.; Mencarelli, A.; Caliendo, G.; Santagada, V.; Distrutti, E.; Santucci, L.; Cirino, G.; Wallace, J.L. Enhanced activity of a hydrogen sulphide-releasing derivative of mesalamine (ATB-429) in a mouse model of colitis. Br. J. Pharmacol., 2007, 150(8), 996-1002.
[] [PMID: 17339831]
Wallace, J.L.; Caliendo, G.; Santagada, V.; Cirino, G. Markedly reduced toxicity of a hydrogen sulphide-releasing derivative of naproxen (ATB-346). Br. J. Pharmacol., 2010, 159(6), 1236-1246.
[] [PMID: 20128814]
Sestito, S.; Nesi, G.; Pi, R.; Macchia, M.; Rapposelli, S. Hydrogen Sulfide: A Worthwhile Tool in the Design of New Multitarget Drugs. Front Chem., 2017, 5, 72.
[] [PMID: 29021980]
Calderone, V.; Martelli, A.; Testai, L.; Citi, V.; Breschi, M.C. Using hydrogen sulfide to design and develop drugs. Expert Opin. Drug Discov., 2016, 11(2), 163-175.
[] [PMID: 26593865]
Rigas, B.; Kashfi, K. Nitric-oxide-donating NSAIDs as agents for cancer prevention. Trends Mol. Med., 2004, 10(7), 324-330.
[] [PMID: 15242680]
Stefano, F.; Distrutti, E. Cyclo-oxygenase (COX) inhibiting nitric oxide donating (CINODs) drugs: a review of their current status. Curr. Top. Med. Chem., 2007, 7(3), 277-282.
[] [PMID: 17305570]
Amareswararao, M.; Babu, Y.R.; Himabindhu, J.; Rajendra Prasad, V.V.S. Synthesis of nitric oxide donating acridone derivatives as cytotoxic agents in cancer. Pharma Chem., 2016, 8(4), 391-398.
Ricciotti, E.; Dovizio, M.; Di Francesco, L.; Anzellotti, P.; Salvatore, T.; Di Francesco, A.; Sciulli, M.G.; Pistritto, G.; Monopoli, A.; Patrignani, P. NCX 4040, a nitric oxide-donating aspirin, exerts anti-inflammatory effects through inhibition of I kappa B-alpha degradation in human monocytes. J. Immunol., 2010, 184(4), 2140-2147.
[] [PMID: 20065114]
Mourad, M.A.; Abdel-Aziz, M.; Abuo-Rahma, Gel-D.; Farag, H.H. Design, synthesis and anticancer activity of nitric oxide donating/chalcone hybrids. Eur. J. Med. Chem., 2012, 54, 907-913.
[] [PMID: 22703846]
Webb, D.J.; Megson, I.L. Nitric oxide donor drugs: current status and future trends. Expert Opin. Investig. Drugs, 2002, 11(5), 587-601.
[] [PMID: 17401442]
Liang, H.; Nacharaju, P.; Friedman, A.; Friedman, J.M. Nitric oxide generating/releasing materials. Future Sci. OA, 2015, 1(1), FSO54.
[] [PMID: 26855790]
Deshpande, S.R.; Satyanarayana, K.; Rao, M.N.A.; Pai, K.V. Nitric oxide modulators: an emerging class of medicinal agents. Indian J. Pharm. Sci., 2012, 74(6), 487-497.
[] [PMID: 23798773]
Vogel, H.G. Drug Discovery and Evaluation Pharmacological Assays; Springer-Verlag: New York, 2002.
Wu, D.; Hu, Q.; Ma, F.; Zhu, Y.Z. Vasorelaxant Effect of a New Hydrogen Sulfide-Nitric Oxide Conjugated Donor in Isolated Rat Aortic Rings through cGMP Pathway. Oxid. Med. Cell. Longev., 2016, 2016 7075682
[] [PMID: 26635911]
Reis, M.R.; de Oliveira Filho, A.A.; Rodrigues, L.S.U.; Araújo, J.P.; Maciel, P.M.P.; de Albuquerque, J.M.; Filho, V.C.; Cáceres, A.; Fregoneze, J.B.; de Medeiros, I.A.; Silva, D.F. Involvement of Potassium Channels in Vasorelaxant Effect Induced by Valeriana prionophylla Standl.Rat Mesenteric Artery; Evid.-Based Complementary Altern. Med, 2013, pp. 1-10.
Bredt, D.S. Endogenous nitric oxide synthesis: biological functions and pathophysiology. Free Radic. Res., 1999, 31(6), 577-596.
[] [PMID: 10630682]
Kimura, H. Production and physiological effects of hydrogen sulfide. Antioxid. Redox Signal., 2014, 20(5), 783-793.
[] [PMID: 23581969]
Novakovic, A.; Bukarica, L.G.; Kanjuh, V.; Heinle, H. Potassium channels-mediated vasorelaxation of rat aorta induced by resveratrol. Basic Clin. Pharmacol. Toxicol., 2006, 99(5), 360-364.
Lunardi, C.N.; Vercesi, J.A.; da Silva, R.S.; Bendhack, L.M. Vasorelaxation induced by the new nitric oxide donor cis-[Ru(Cl)(bpy)(2)(NO)](PF(6)) is due to activation of K(Ca) by a cGMP-dependent pathway. Vascul. Pharmacol., 2007, 47(2-3), 139-144.
[] [PMID: 17602893]
Mendes-Júnior, Ld.; Guimarães, D.D.; Gadelha, D.D.A.; Diniz, T.F.; Brandão, M.C.R.; Athayde-Filho, P.F.; Lemos, V.S.; França-Silva, Mdo.S.; Braga, V.A. The new nitric oxide donor cyclohexane nitrate induces vasorelaxation, hypotension, and antihypertensive effects via NO/cGMP/PKG pathway. Front. Physiol., 2015, 6(243), 243.
[] [PMID: 26379557]
Dantas, B.P.V.; Ribeiro, T.P.; Assis, V.L.; Furtado, F.F.; Assis, K.S.; Alves, J.S.; Silva, T.M.S.; Camara, C.A.; França-Silva, M.S.; Veras, R.C.; Medeiros, I.A.; Alencar, J.L.; Braga, V.A. Vasorelaxation induced by a new naphthoquinone-oxime is mediated by NO-sGC-cGMP pathway. Molecules, 2014, 19(7), 9773-9785.
[] [PMID: 25006785]
Yu, S.M.; Kuo, S.C. Vasorelaxant effect of isoliquiritigenin, a novel soluble guanylate cyclase activator, in rat aorta. Br. J. Pharmacol., 1995, 114(8), 1587-1594.
[] [PMID: 7599926]

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