Animal models for the study of primary and secondary hypertension in humans (Review)

Lin,Hiu Yu; Lee,Yee Ting; Chan,Yin Wah; Tse,Gary

doi:10.3892/br.2016.784

Animal models for the study of primary and secondary hypertension in humans (Review)

Authors:
- Hiu Yu Lin
- Yee Ting Lee
- Yin Wah Chan
- Gary Tse
View Affiliations

Affiliations: School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, SAR, P.R. China, School of Biological Sciences, University of Cambridge, Cambridge CB2 1AG, UK, Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong, SAR, P.R. China
Published online on: October 18, 2016 https://doi.org/10.3892/br.2016.784
Pages: 653-659
Copyright : © Lin et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Hypertension is a significant cause of morbidity and mortality worldwide. It is defined as systolic and diastolic blood pressures (SBP/DBP) >140 and 90 mmHg, respectively. Individuals with an SBP between 120 and 139, or DBP between 80 and 89 mmHg, are said to exhibit pre‑hypertension. Hypertension can have primary or secondary causes. Primary or essential hypertension is a multifactorial disease caused by interacting environmental and polygenic factors. Secondary causes are renovascular hypertension, renal disease, endocrine disorders and other medical conditions. The aim of the present review article was to examine the different animal models that have been generated for studying the molecular and physiological mechanisms underlying hypertension. Their advantages, disadvantages and limitations will be discussed.

View Figures

View References

1	Chen R, Dharmarajan K, Kulkarni VT, Punnanithinont N, Gupta A, Bikdeli B, Mody PS and Ranasinghe I: Most important outcomes research papers on hypertension. Circ Cardiovasc Qual Outcomes. 6:e26–e35. 2013. View Article : Google Scholar : PubMed/NCBI
2	Galosy RA, Clarke LK, Vasko MR and Crawford IL: Neurophysiology and neuropharmacology of cardiovascular regulation and stress. Neurosci Biobehav Rev. 5:137–175. 1981. View Article : Google Scholar : PubMed/NCBI
3	Weinberger MH: Salt sensitivity of blood pressure in humans. Hypertension. 27:481–490. 1996. View Article : Google Scholar : PubMed/NCBI
4	Sarikonda KV, Watson RE, Opara OC and Dipette DJ: Experimental animal models of hypertension. J Am Soc Hypertens. 3:158–165. 2009. View Article : Google Scholar : PubMed/NCBI
5	Lerman LO, Chade AR, Sica V and Napoli C: Animal models of hypertension: An overview. J Lab Clin Med. 146:160–173. 2005. View Article : Google Scholar : PubMed/NCBI
6	Tse G, Tse V and Yeo JM: Ventricular anti-arrhythmic effects of heptanol in hypokalaemic, Langendorff-perfused mouse hearts. Biomed Rep. 4:313–324. 2016.PubMed/NCBI
7	Tse G, Tse V, Yeo JM and Sun B: Atrial anti arrhythmic effects of heptanol in Langendorff perfused mouse hearts. PLoS One. 11:e01488582016. View Article : Google Scholar : PubMed/NCBI
8	Tse G, Wong ST, Tse V and Yeo JM: Restitution analysis of alternans using dynamic pacing and its comparison with S1S2 restitution in heptanol-treated, hypokalaemic Langendorff-perfused mouse hearts. Biomed Rep. 4:673–680. 2016.PubMed/NCBI
9	Tse G, Sun B, Wong ST, Tse V and Yeo JM: Ventricular anti arrhythmic effects of hypercalcaemia treatment in hyperkalaemic, Langendorff perfused mouse hearts. Biomed Rep. 5:301–310. 2016.PubMed/NCBI
10	Tse G, Hothi SS, Grace AA and Huang CL: Ventricular arrhythmogenesis following slowed conduction in heptanol-treated, Langendorff-perfused mouse hearts. J Physiol Sci. 62:79–92. 2012. View Article : Google Scholar : PubMed/NCBI
11	Tse G and Yeo JM: Conduction abnormalities and ventricular arrhythmogenesis: The roles of sodium channels and gap junctions. Int J Cardiol Heart Vasc. 9:75–82. 2015.PubMed/NCBI
12	Tse G, Yeo JM, Tse V, Kwan SK and Sun B: Gap junction inhibition by heptanol increases ventricular arrhythmogenicity by decreasing conduction velocity without affecting repolarization properties or myocardial refractoriness in Langendorff perfused mouse hearts. Mol Med Rep. (In press). PubMed/NCBI
13	Leong XF, Ng CY and Jaarin K: Animal models in cardiovascular research: Hypertension and atherosclerosis. BioMed Res Int. 2015:5287572015. View Article : Google Scholar : PubMed/NCBI
14	Doggrell SA and Brown L: Rat models of hypertension, cardiac hypertrophy and failure. Cardiovasc Res. 39:89–105. 1998. View Article : Google Scholar : PubMed/NCBI
15	Goldblatt H, Lynch J, Hanzal RF and Summerville WW: Studies on experimental: I. the production of persistent elevation of systolic blood pressure by means of renal ischenmia. J Exp Med. 9:347–379. 1934. View Article : Google Scholar
16	Gross DR: Animal models of hypertensionAnimal models in cardiovascular research. Springer; Netherlands, Dordrecht: pp. 475–482. 1994, View Article : Google Scholar
17	Terris JM and Simmonds RC: The Yucatan miniature swine: An improved pig model for the study of desoxycorticosterone-acetate (DOCA) and aldosterone hypertension. Proc Soc Exp Biol Med. 171:79–82. 1982. View Article : Google Scholar : PubMed/NCBI
18	Yagil Y and Yagil C: Genetic models of hypertension in experimental animals. Exp Nephrol. 9:1–9. 2001. View Article : Google Scholar : PubMed/NCBI
19	Twigger S, Lu J, Shimoyama M, Chen D, Pasko D, Long H, Ginster J, Chen CF, Nigam R, Kwitek A, et al: Rat Genome Database (RGD): Mapping disease onto the genome. Nucleic Acids Res. 30:125–128. 2002. View Article : Google Scholar : PubMed/NCBI
20	Trippodo NC and Frohlich ED: Similarities of genetic (spontaneous) hypertension. Man and rat. Circ Res. 48:309–319. 1981. View Article : Google Scholar : PubMed/NCBI
21	Stoll M and Jacob HJ: Genetic rat models of hypertension: Relationship to human hypertension. Curr Hypertens Rep. 3:157–164. 2001. View Article : Google Scholar : PubMed/NCBI
22	Fuentes RM, Notkola IL, Shemeikka S, Tuomilehto J and Nissinen A: Familial aggregation of blood pressure: A population-based family study in eastern Finland. J Hum Hypertens. 14:441–445. 2000. View Article : Google Scholar : PubMed/NCBI
23	Perry IJ, Whincup PH and Shaper AG: Environmental factors in the development of essential hypertension. Br Med Bull. 50:246–259. 1994.PubMed/NCBI
24	Williams SM, Haines JL and Moore JH: The use of animal models in the study of complex disease: All else is never equal or why do so many human studies fail to replicate animal findings? BioEssays. 26:170–179. 2004. View Article : Google Scholar : PubMed/NCBI
25	Fuster V, Lie JT, Badimon L, Rosemark JA, Badimon JJ and Bowie EJ: Spontaneous and diet-induced coronary atherosclerosis in normal swine and swine with von Willebrand disease. Arteriosclerosis. 5:67–73. 1985. View Article : Google Scholar : PubMed/NCBI
26	Fekete A, Rényi Vámos A and Szitás A: Experimental model of renovascular hypertension in dogs. Int Urol Nephrol. 2:391–400. 1970. View Article : Google Scholar
27	Hasiwa N, Bailey J, Clausing P, Daneshian M, Eileraas M, Farkas S, Gyertyán I, Hubrecht R, Kobel W, Krummenacher G, et al: Critical evaluation of the use of dogs in biomedical research and testing in Europe. ALTEX. 28:326–340. 2011. View Article : Google Scholar : PubMed/NCBI
28	Wiesel P, Mazzolai L, Nussberger J and Pedrazzini T: Two-kidney, one clip and one-kidney, one clip hypertension in mice. Hypertension. 29:1025–1030. 1997. View Article : Google Scholar : PubMed/NCBI
29	Okamura T, Miyazaki M, Inagami T and Toda N: Vascular renin-angiotensin system in two-kidney, one clip hypertensive rats. Hypertension. 8:560–565. 1986. View Article : Google Scholar : PubMed/NCBI
30	Yamasaki S: Divided renal and caval vein plasma renin activity in two-kidney two-clip hypertension in rabbits and variations of blood pressure, plasma volume and renal function following unilateral nephrectomy. J Urol. 138:1457–1460. 1987.PubMed/NCBI
31	Sato K, Abe K, Seino M, Yasujima M, Imai Y, Sato M, Hiwatari M, Omata K, Tanno M, Kohzuki M, et al: Renal vein plasma renin activity in patients with unilateral renovascular hypertension. Jpn Circ J. 52:431–436. 1988. View Article : Google Scholar : PubMed/NCBI
32	Sawamura T and Nakada T: Role of dopamine in the striatum, renin-angiotensin system and renal sympathetic nerve on the development of two-kidney, one-clip Goldblatt hypertension. J Urol. 155:1108–1111. 1996. View Article : Google Scholar : PubMed/NCBI
33	Zeng J, Zhang Y, Mo J, Su Z and Huang R: Two kidney, two clip renovascular hypertensive rats can be used as stroke prone rats. Stroke. 29:1708–1713. 1998. View Article : Google Scholar : PubMed/NCBI
34	Murphy WR, Coleman TG, Smith TL and Stanek KA: Effects of graded renal artery constriction on blood pressure, renal artery pressure, and plasma renin activity in Goldblatt hypertension. Hypertension. 6:68–74. 1984. View Article : Google Scholar : PubMed/NCBI
35	Feldman L, Beberashvili I, Averbukh Z and Weissgarten J: Renal artery stenosis of solitary kidney: The dilemma. Ren Fail. 26:525–529. 2004. View Article : Google Scholar : PubMed/NCBI
36	Brunner HR, Kirshman JD, Sealey JE and Laragh JH: Hypertension of renal origin: Evidence for two different mechanisms. Science. 174:1344–1346. 1971. View Article : Google Scholar : PubMed/NCBI
37	Preston RA and Epstein M: Renal parenchymal disease and hypertension. Semin Nephrol. 15:138–151. 1995.PubMed/NCBI
38	van Koppen A, Verhaar MC, Bongartz LG and Joles JA: 5/6th nephrectomy in combination with high salt diet and nitric oxide synthase inhibition to induce chronic kidney disease in the Lewis rat. J Vis Exp. 77:e503982013.
39	Moore S and Mersereau WA: Microembolic renal ischemia, hypertension, and nephrosclerosis. Arch Pathol. 85:623–630. 1968.PubMed/NCBI
40	Page IH: A method for producing persistent hypertension by cellophane. Science. 89:273–274. 1939. View Article : Google Scholar : PubMed/NCBI
41	Selye H, Hall CE and Rowley EM: Malignant hypertension produced by treatment with desoxycorticosterone acetate and sodium chloride. Can Med Assoc J. 49:88–92. 1943.PubMed/NCBI
42	Iyer A, Chan V and Brown L: The DOCA-salt hypertensive rat as a model of cardiovascular oxidative and inflammatory stress. Curr Cardiol Rev. 6:291–297. 2010. View Article : Google Scholar : PubMed/NCBI
43	Williams SK and Ogedegbe G: Unraveling the mechanism of renin-angiotensin- aldosterone system activation and target organ damage in hypertensive blacks. Hypertension. 59:10–11. 2012. View Article : Google Scholar : PubMed/NCBI
44	Wilson KM, Sumners C, Hathaway S and Fregly MJ: Mineralocorticoids modulate central angiotensin II receptors in rats. Brain Res. 382:87–96. 1986. View Article : Google Scholar : PubMed/NCBI
45	Möhring J, Möhring B, Petri M and Haack D: Vasopressor role of ADH in the pathogenesis of malignant DOC hypertension. Am J Physiol. 232:F260–F269. 1977.PubMed/NCBI
46	Li L, Chu Y, Fink GD, Engelhardt JF, Heistad DD and Chen AF: Endothelin-1 stimulates arterial VCAM-1 expression via NADPH oxidase-derived superoxide in mineralocorticoid hypertension. Hypertension. 42:997–1003. 2003. View Article : Google Scholar : PubMed/NCBI
47	Matsumura Y, Hashimoto N, Taira S, Kuro T, Kitano R, Ohkita M, Opgenorth TJ and Takaoka M: Different contributions of endothelin-A and endothelin-B receptors in the pathogenesis of deoxycorticosterone acetate-salt-induced hypertension in rats. Hypertension. 33:759–765. 1999. View Article : Google Scholar : PubMed/NCBI
48	Zambraski EJ, Ciccone CD and Izzo JL Jr: The role of the sympathetic nervous system in 2-kidney DOCA-hypertensive Yucatan miniature swine. Clin Exp Hypertens A. 8:411–424. 1986.PubMed/NCBI
49	Dahl LK, Knudsen KD, Heine M and Leitl G: Effects of chronic excess salt ingestion. Genetic influence on the development of salt hypertension in parabiotic rats: Evidence for a humoral factor. J Exp Med. 126:687–699. 1967. View Article : Google Scholar : PubMed/NCBI
50	McCubbin JW, DeMoura RS, Page IH and Olmsted F: Arterial hypertension elicited by subpressor amounts of angiotensin. Science. 149:1394–1395. 1965. View Article : Google Scholar : PubMed/NCBI
51	Moncada S and Higgs A: The L-arginine-nitric oxide pathway. N Engl J Med. 329:2002–2012. 1993. View Article : Google Scholar : PubMed/NCBI
52	Ribeiro MO, Antunes E, de Nucci G, Lovisolo SM and Zatz R: Chronic inhibition of nitric oxide synthesis. A new model of arterial hypertension. Hypertension. 20:298–303. 1992. View Article : Google Scholar : PubMed/NCBI
53	Lahera V, Salazar J, Salom MG and Romero JC: Deficient production of nitric oxide induces volume-dependent hypertension. J Hypertens Suppl. 10:(Suppl 7). S173–S177. 1992. View Article : Google Scholar : PubMed/NCBI
54	Zatz R and Baylis C: Chronic nitric oxide inhibition model six years on. Hypertension. 32:958–964. 1998. View Article : Google Scholar : PubMed/NCBI
55	Buñag RD, Takeda K and Riley E: Spontaneous remission of hypertension in awake rats chronically exposed to shaker stress. Hypertension. 2:311–318. 1980. View Article : Google Scholar : PubMed/NCBI
56	Smookler HH, Goebel KH, Siegel MI and Clarke DE: Hypertensive effects of prolonged auditory, visual, and motion stimulation. Fed Proc. 32:2105–2110. 1973.PubMed/NCBI
57	McCann SM, Rothballer AB, Yeakel EH and Shenkin HA: Adrenalectomy and blood pressure of rats subjected to auditory stimulation. Am J Physiol. 155:128–131. 1948.PubMed/NCBI
58	Kaufman LN, Peterson MM and Smith SM: Hypertension and sympathetic hyperactivity induced in rats by high-fat or glucose diets. Am J Physiol. 260:E95–E100. 1991.PubMed/NCBI
59	Fregly MJ: Effects of Extremes of temperature on hypertensive rats. Am J Physiol. 176:275–281. 1954.PubMed/NCBI
60	Papanek PE, Wood CE and Fregly MJ: Role of the sympathetic nervous system in cold-induced hypertension in rats. J Appl Physiol (1985). 71:300–306. 1991.PubMed/NCBI
61	Donaldson GC, Robinson D and Allaway SL: An analysis of arterial disease mortality and BUPA health screening data in men, in relation to outdoor temperature. Clin Sci (Lond). 92:261–268. 1997. View Article : Google Scholar : PubMed/NCBI
62	Brennan PJ, Greenberg G, Miall WE and Thompson SG: Seasonal variation in arterial blood pressure. Br Med J (Clin Res Ed). 285:919–923. 1982. View Article : Google Scholar : PubMed/NCBI
63	Coste SC, Qi Y, Brooks VL, McCarron DA and Hatton DC: Captopril and stress-induced hypertension in the borderline hypertensive rat. J Hypertens. 13:1391–1398. 1995. View Article : Google Scholar : PubMed/NCBI
64	Hwang IS, Ho H, Hoffman BB and Reaven GM: Fructose-induced insulin resistance and hypertension in rats. Hypertension. 10:512–516. 1987. View Article : Google Scholar : PubMed/NCBI
65	Garcia EA, Newhouse S, Caulfield MJ and Munroe PB: Genes and hypertension. Curr Pharm Des. 9:1679–1689. 2003. View Article : Google Scholar : PubMed/NCBI
66	Tabara Y, Kohara K and Miki T: Millennium Genome Project for Hypertension: Hunting for genes for hypertension: The millennium genome project for hypertension. Hypertens Res. 35:567–573. 2012. View Article : Google Scholar : PubMed/NCBI
67	Mann JF, Phillips MI, Dietz R, Haebara H and Ganten D: Effects of central and peripheral angiotensin blockade in hypertensive rats. Am J Physiol. 234:H629–H637. 1978.PubMed/NCBI
68	Yan L, Zhang JD, Wang B, Lv YJ, Jiang H, Liu GL, Qiao Y, Ren M and Guo XF: Quercetin inhibits left ventricular hypertrophy in spontaneously hypertensive rats and inhibits angiotensin II-induced H9C2 cells hypertrophy by enhancing PPAR-γ expression and suppressing AP-1 activity. PLoS One. 8:e725482013. View Article : Google Scholar : PubMed/NCBI
69	Bagby SP, McDonald WJ and Mass RD: Serial renin-angiotensin studies in spontaneously hypertensive and Wistar-Kyoto normotensive rats. Transition from normal- to high-renin status during the established phase of spontaneous hypertension. Hypertension. 1:347–354. 1979. View Article : Google Scholar : PubMed/NCBI
70	Okamoto K and Aoki K: Development of a strain of spontaneously hypertensive rats. Jpn Circ J. 27:282–293. 1963. View Article : Google Scholar : PubMed/NCBI
71	Kurtz TW and Morris RC Jr: Biological variability in Wistar-Kyoto rats. Implications for research with the spontaneously hypertensive rat. Hypertension. 10:127–131. 1987. View Article : Google Scholar : PubMed/NCBI
72	Tobian L, Lange JM, Ulm KM, Wold LJ and Iwai J: Potassium prevents death from strokes in hypertensive rats without lowering blood pressure. J Hypertens Suppl. 2:S363–S366. 1984.PubMed/NCBI
73	Mashimo T, Nabika T, Matsumoto C, Tamada T, Ueno K, Sawamura M, Ikeda K, Kato N, Nara Y and Yamori Y: Aging and salt-loading modulate blood pressure QTLs in rats. Am J Hypertens. 12:1098–1104. 1999. View Article : Google Scholar : PubMed/NCBI
74	Smirk FH and Hall WH: Inherited hypertension in rats. Nature. 182:727–728. 1958. View Article : Google Scholar : PubMed/NCBI
75	Vincent M, Bornet H, Berthezene F, Dupont J and Sassard J: Thyroid function and blood pressure in two new strains of spontaneously hypertensive and normotensive rats. Clin Sci Mol Med. 54:391–395. 1978.PubMed/NCBI
76	Vincent M, Gomez-Sanchez CE, Bataillard A and Sassard J: Steroids during development of genetic hypertension in rats of Lyon strain. Am J Physiol. 257:H506–H510. 1989.PubMed/NCBI
77	Rapp JP and Dene H: Development and characteristics of inbred strains of Dahl salt-sensitive and salt-resistant rats. Hypertension. 7:340–349. 1985. View Article : Google Scholar : PubMed/NCBI
78	Dahl LK, Heine M and Tassinari L: Effects of chronic excess salt ingestion. Further demonstration that genetic factors influence the development of hypertension: Evidence from experimental hypertension due to cortisone and to adrenal regeneration. J Exp Med. 122:533–545. 1965. View Article : Google Scholar : PubMed/NCBI
79	Deng Y and Rapp JP: Cosegregation of blood pressure with angiotensin converting enzyme and atrial natriuretic peptide receptor genes using Dahl salt-sensitive rats. Nat Genet. 1:267–272. 1992. View Article : Google Scholar : PubMed/NCBI
80	Zamir N, Gutman Y and Ben-Ishay D: Hypertension and brain catecholamine distribution in the Hebrew University Sabra, H and N rats. Clin Sci Mol Med Suppl. 4:105s–107s. 1978.PubMed/NCBI
81	Kuijpers MH and Gruys E: Spontaneous hypertension and hypertensive renal disease in the fawn-hooded rat. Br J Exp Pathol. 65:181–190. 1984.PubMed/NCBI
82	Dobrian AD, Davies MJ, Prewitt RL and Lauterio TJ: Development of hypertension in a rat model of diet-induced obesity. Hypertension. 35:1009–1015. 2000. View Article : Google Scholar : PubMed/NCBI
83	Mullins LJ, Bailey MA and Mullins JJ: Hypertension, kidney, and transgenics: A fresh perspective. Physiol Rev. 86:709–746. 2006. View Article : Google Scholar : PubMed/NCBI
84	Lagrange D and Fournié GJ: Generation of congenic and consomic rat strains. Methods Mol Biol. 597:243–266. 2010. View Article : Google Scholar : PubMed/NCBI
85	Cowley AW Jr, Liang M, Roman RJ, Greene AS and Jacob HJ: Consomic rat model systems for physiological genomics. Acta Physiol Scand. 181:585–592. 2004. View Article : Google Scholar : PubMed/NCBI
86	Mullins JJ, Peters J and Ganten D: Fulminant hypertension in transgenic rats harbouring the mouse Ren-2 gene. Nature. 344:541–544. 1990. View Article : Google Scholar : PubMed/NCBI
87	Montgomery HE, Kiernan LA, Whitworth CE, Fleming S, Unger T, Gohlke P, Mullins JJ and McEwan JR: Inhibition of tissue angiotensin converting enzyme activity prevents malignant hypertension in TGR(mREN2)27. J Hypertens. 16:635–643. 1998. View Article : Google Scholar : PubMed/NCBI
88	Sigmund CD, Jones CA, Kane CM, Wu C, Lang JA and Gross KW: Regulated tissue- and cell-specific expression of the human renin gene in transgenic mice. Circ Res. 70:1070–1079. 1992. View Article : Google Scholar : PubMed/NCBI
89	Chung O, Schips T, Rohmeiss P, Gretz N, Strauch M and Unger T: Protein excretion and renal adaptation of transgenic mRen2 rats to changing oral sodium loads. J Hypertens Suppl. 11:S188–S189. 1993. View Article : Google Scholar : PubMed/NCBI
90	Tse G: Novel conduction repolarization indices for the stratification of arrhythmic risk. J Geriatr Cardiol. (In press). PubMed/NCBI
91	Tse G: (Tpeak Tend)/QRS and (Tpeak Tend)/(QT x QRS): Novel markers for predicting arrhythmic risk in the Brugada syndrome. Europace. (In press).
92	Tse G and Yan BP: Electrophysiological mechanisms of long and short QT syndromes: Insights from mouse models. IJC Heart & Vasculature. (In press).
93	Tse G and Yan BP: Novel arrhythmic risk markers incorporating QRS dispersion: QRSd × (Tpeak - Tend)/QRS and QRSd × (Tpeak - Tend)/(QT × QRS). Ann Noninvasive Electrocardiol. Aug 18–2016.(Epub ahead of print). View Article : Google Scholar : PubMed/NCBI
94	Tse G, Lai ET, Lee AP, Yan BP and Wong SH: Electrophysiological mechanisms of gastrointestinal arrhythmogenesis: Lessons from the heart. Front Physiol. 7:2302016. View Article : Google Scholar : PubMed/NCBI
95	Tse G, Wong ST, Tse V and Yeo JM: Variability in local action potential durations, dispersion of repolarization and wavelength restitution in aged wild type and Scn5a/− mouse hearts modelling human Brugada syndrome. J Geriatr Cardiol. (In press). PubMed/NCBI
96	Tse G: Mechanisms of cardiac arrhythmias. J Arrhythm. 32:75–81. 2016. View Article : Google Scholar : PubMed/NCBI
97	Tse G, Yeo JM, Chan YW, Lai ET and Yan BP: What is the arrhythmic substrate in viral myocarditis? Insights from clinical and animal studies. Front Physiol. 7:3082016. View Article : Google Scholar : PubMed/NCBI
98	Tse G and Yan BP: Traditional and novel electrocardiographic conduction and repolarization markers of sudden cardiac death. Europace. (In press).
99	Sun B, Chen Z, Gu J, et al: The roles of tight and gap junctions in the pathogenesis of high fat diet induced atherosclerosis. Int J Clin Exp Pathol. (In press).
100	Sun Z, Cade R, Zhang Z, Alouidor J and Van H: Angiotensinogen gene knockout delays and attenuates cold-induced hypertension. Hypertension. 41:322–327. 2003. View Article : Google Scholar : PubMed/NCBI
101	Shesely EG, Maeda N, Kim H-S, Desai KM, Krege JH, Laubach VE, Sherman PA, Sessa WC and Smithies O: Elevated blood pressures in mice lacking endothelial nitric oxide synthase. Proc Natl Acad Sci USA. 93:13176–13181. 1996. View Article : Google Scholar : PubMed/NCBI
102	Sugaya T, Nishimatsu S, Tanimoto K, Takimoto E, Yamagishi T, Imamura K, Goto S, Imaizumi K, Hisada Y, Otsuka A, et al: Angiotensin II type 1a receptor-deficient mice with hypotension and hyperreninemia. J Biol Chem. 270:18719–18722. 1995. View Article : Google Scholar : PubMed/NCBI
103	Geller DS, Farhi A, Pinkerton N, Fradley M, Moritz M, Spitzer A, Meinke G, Tsai FT, Sigler PB and Lifton RP: Activating mineralocorticoid receptor mutation in hypertension exacerbated by pregnancy. Science. 289:119–123. 2000. View Article : Google Scholar : PubMed/NCBI
104	Shimkets RA, Warnock DG, Bositis CM, Nelson-Williams C, Hansson JH, Schambelan M, Gill JR Jr, Ulick S, Milora RV, Findling JW, et al: Liddle's syndrome: Heritable human hypertension caused by mutations in the beta subunit of the epithelial sodium channel. Cell. 79:407–414. 1994. View Article : Google Scholar : PubMed/NCBI
105	Tse G, Wong ST, Tse V, Lee YT, Lin HY and Yeo JM: Cardiac dynamics: Alternans and arrhythmogenesis. J Arrhythm. (In press).
106	Tse G, Wong ST, Tse V and Yeo JM: Monophasic action potential recordings: Which is the recording electrode? J Basic Clin Physiol Pharmacol. Apr 30–2016.(Epub ahead of print). View Article : Google Scholar : PubMed/NCBI
107	Tse G, Lai ET, Yeo JM, Tse V and Wong SH: Mechanisms of electrical activation and conduction in the gastrointestinal system: Lessons from cardiac electrophysiology. Front Physiol. 7:1822016. View Article : Google Scholar : PubMed/NCBI
108	Tse G, Wong ST, Tse V and Yeo JM: Depolarization vs. repolarization: What is the mechanism of ventricular arrhythmogenesis underlying sodium channel haploinsufficiency in mouse hearts? Acta Physiol (Oxf). (In press).
109	Chen Z, Sun B, Tse G, Jiang J and Xu W: Reversibility of both sinus node dysfunction and reduced HCN4 mRNA expression level in an atrial tachycardia pacing model of tachycardia bradycardia syndrome in rabbit hearts. Int J Clin Exp Pathol. (In press).
110	Tse G, Lai ET, Tse V and Yeo JM: Molecular and electrophysiological mechanisms underlying cardiac arrhythmogenesis in diabetes mellitus. J Diabetes Res. 2016:1–8. 2016. View Article : Google Scholar
111	Tse G: Both transmural dispersion of repolarization and transmural dispersion of refractoriness are poor predictors of arrhythmogenicity: A role for the index of Cardiac Electrophysiological Balance (QT/QRS)? J Geriatr Cardiol. (In press). PubMed/NCBI
112	Tse G, Wong ST, Tse V and Yeo JM: Determination of action potential wavelength restitution in Scn5a/- mouse hearts modelling human Brugada syndrome. J Physiol. (In press).
113	Choy L, Yeo JM, Tse V, Chan SP and Tse G: Cardiac disease and arrhythmogenesis: Mechanistic insights from mouse models. Int J Cardiol Heart Vasc. 12:1–10. 2016.PubMed/NCBI
114	Hu Z, Chen Z, Wang Y, et al: Effects of granulocyte colony stimulating factor on rabbit carotid and swine heart models of chronic obliterative arterial disease. Mol Med Rep. (In press).
115	Tse G, Yan BP, Chan YW, Tian XY and Huang Y: Reactive oxygen species, endoplasmic reticulum stress and mitochondrial dysfunction: The link with cardiac arrhythmogenesis. Front Physiol. 7:3132016. View Article : Google Scholar : PubMed/NCBI
116	Tse G, Ali A, Prasad SK, Vassiliou V and Raphael CE: Atypical case of post partum cardiomyopathy: an overlap syndrome with arrhythmogenic right ventricular cardiomyopathy? BJR\|case reports. 1:20150182. 2015.
117	Tse G, Ali A, Alpendurada F, Prasad S, Raphael CE and Vassiliou V: Tuberculous constrictive pericarditis. Res Cardiovasc Med. 4:e296142015. View Article : Google Scholar : PubMed/NCBI
118	Vassiliou V, Chin C, Perperoglou A, Tse G, Ali A, Raphael C, Jabbour A, Newby D, Pennell D, Dweck M, et al: 93 ejection fraction by cardiovascular magnetic resonance predicts adverse outcomes post aortic valve replacement. Heart. 100:(Suppl 3). A53–A54. 2014. View Article : Google Scholar
119	Hasenfuss G: Animal models of human cardiovascular disease, heart failure and hypertrophy. Cardiovasc Res. 39:60–76. 1998. View Article : Google Scholar : PubMed/NCBI