Regulation of therapeutic apoptosis: A potential target in controlling hypertensive organ damage

Canadian Journal of Physiology and Pharmacology

Volumn 83, Issue 1, 2005, Pages 29-41

  DeBlois, Denis ^a   Tea, Bun Seng ^a   Beaudry, Diane ^a   Hamet, Pavel ^a  

^a CENTRE HOSPITALIER DE L UNIVERSITÉ DE MONTRÉAL   (Canada)

Author keywords

Apoptosis; Growth; Hyperplasia; Hypertension; Nifedipine

Indexed keywords

BETA ADRENERGIC RECEPTOR BLOCKING AGENT; CALCIUM CHANNEL BLOCKING AGENT; NIFEDIPINE; RENIN INHIBITOR;

ANIMAL EXPERIMENT; ANIMAL MODEL; APOPTOSIS; CELL CYCLE; CELL DIVISION; CELL GROWTH; CELL SUBPOPULATION; CELL SURVIVAL; CONFERENCE PAPER; CONTROLLED STUDY; DRUG INTERMITTENT THERAPY; FIBROBLAST; HEART VENTRICLE HYPERTROPHY; HYPERTENSION; NONHUMAN; PRIORITY JOURNAL; RAT; RENIN ANGIOTENSIN ALDOSTERONE SYSTEM; SMOOTH MUSCLE FIBER; SPONTANEOUSLY HYPERTENSIVE RAT;

ANIMALS; ANTIHYPERTENSIVE AGENTS; APOPTOSIS; CARDIOVASCULAR SYSTEM; HUMANS; HYPERTENSION; HYPERTROPHY;

EID: 19944405467     PISSN: 00084212     EISSN: None     Source Type: Journal    
DOI: 10.1139/y05-001     Document Type: Conference Paper

References (131)

1. Adachi, Y., Saito, Y., Kishimoto, I., Harada, M., Kuwahara, K., Takahashi, N. et al. 2003. Angiotensin II type 2 receptor deficiency exacerbates heart failure and reduces survival after acute myocardial infarction in mice. Circulation, 107: 2406-2408.
2. i-independent signaling in C7-MDCK cells. J. Biol. Chem. 280: 832-839.
3. Alric, C., Pecher, C., Cellier, E., Schanstra, J.P., Poirier, B., Chevalier, J. et al. 2002. Inhibition of IGF-I-induced Erk 1 and 2 activation and mitogenesis in mesangial cells by bradykinin. Kidney Int. 62: 412-421.
4. Anderson, N.H., Devlin, A.M., Graham, D., Morton, J.J., Hamilton, C.A., Reid, J.L. et al. 1999. Telemetry for cardiovascular monitoring in a pharmacological study: new approaches to data analysis. Hypertension, 33(Pt. 2): 248-255.
5. Andreassen, P.R., Lohez, O.D., Lacroix, F.B., and Margolis, R.L. 2001. Tetraploid state induces p53-dependent arrest of non-transformed mammalian cells in G1. Mol. Biol. Cell, 12: 1315-1328.
6. Anversa, P., Olivetti, G., Leri, A., Liu, Y., and Kajstura, J. 1997. Myocyte cell death and ventricular remodeling. Curr. Opin. Nephrol. Hypertens. 6: 169-176.
7. Barrett, T.B., Sampson, P., Owens, G.K., Schwartz, S.M., and Benditt, E.P. 1983. Polyploid nuclei in human artery wall smooth muscle cells. Proc. Natl. Acad. Sci. USA, 80: 882-885.
8. Bayer, I.M., Adamson, S.L., and Langille, B.L. 1999. Atrophic remodeling of the artery-cuffed artery. Arterioscler. Thromb. Vasc. Biol. 19: 1499-1505.
9. Bennett, M.R., Evan, G.I., and Schwartz, S.M. 1995. Apoptosis of human vascular smooth muscle cells derived from normal vessels and coronary atherosclerotic plaques. J. Clin. Invest. 95: 2266-2274.
10. Bennett, M., Macdonald, K., Chan, S.W., Luzio, J.P., Simari, R., and Weissberg, P. 1998. Cell surface trafficking of fas: a rapid mechanism of p53-mediated apoptosis. Science (Wash., DC) 282: 290-293.
11. Black, M.J., Adams, M.A., Bobik, A., Campbell, J.H., and Campbell, G.R. 1988. Vascular smooth muscle polyploidy in the development and regression of hypertension. Clin. Exp. Pharmacol. Physiol. 15: 345-348.
12. Black, M.J., Adams, M.A., Bobik, A., Campbell, J.H., and Campbell, G.R. 1989. Effect of enalapril on aortic smooth muscle cell polyploidy in the spontaneously hypertensive rat. J. Hypertens. 7: 997-1003.
13. Blanco-Colio, L.M., Villa, A., Ortego, M., Hernandez-Presa, M.A., Pascual, A., Plaza, J.J., and Egido, J. 2002. 3-Hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitors, atorvastatin and simvastatin, induce apoptosis of vascular smooth muscle cells by downregulation of Bcl-2 expression and Rho A prenylation. Atherosclerosis, 161: 17-26.
14. Bouthillier, J., deBlois, D., and Marceau, F. 1987. Studies on the induction of pharmacological responses to des-Arg9-bradykinin in vitro and in vivo. Br. J. Pharmacol. 92: 257-264.
15. Buemi, M., Allegra, A., Senatore, M., Marino, D., Medici, M.A., Aloisi, C., Di Pasquale, G., and Corica, F. 1999. Pro-apoptotic effect of fluvastatin on human smooth muscle cells. Eur. J. Pharmacol. 370: 201-203.
16. Campbell, S.E., Turek, Z., Rakusan, K., and Kazda, S. 1993. Cardiac structural remodelling after treatment of spontaneously hypertensive rats with nifedipine or nisoldipine. Cardiovasc. Res. 27: 1350-1358.
17. Cao, Y., Li, H., Mu, F.T., Ebisui, O., Funder, J.W., and Liu, J.P. 2002. Telomerase activation causes vascular smooth muscle cell proliferation in genetic hypertension. FASEB J. 16: 96-98.
18. Cellier, E., Mage, M., Duchene, J., Pecher, C., Couture, R., Bascands, J.L., and Girolami, J.P. 2003. Bradykinin reduces growth factor-induced glomerular ERK1/2 phosphorylation. Am. J. Physiol. Renal Physiol. 284: F282-F292.
19. Cheng, A., Wang, S., Yang, D., Xiao, R., and Mattson, M.P. 2003. Calmodulin mediates brain-derived neurotrophic factor cell survival signaling upstream of Akt kinase in embryonic neocortical neurons. J. Biol. Chem. 278(9): 7591-7599.
20. Cho, A., Courtman, D.W., and Langille, B.L. 1995. Apoptosis (programmed cell death) in arteries of the neonatal lamb. Circ. Res. 76: 168-175.
21. Cho, A., Mitchell, L., Koopmans, D., and Langille, B.L. 1997. Effects of changes in blood flow rate on cell death and cell proliferation in carotid arteries of immature rabbits. Circ. Res. 81: 328-337.
22. Chow, L.M., and Veillette, A. 1995. The Src and Csk families of tyrosine protein kinases in hemopoietic cells. Semin. Immunol. 7: 207-226.
23. Ciciarello, M., Mangiacasale, R., Casenghi, M., Zaira Limongi, M., D'Angelo, M., Soddu, S. et al. 2001. p53 displacement from centrosomes and p53-mediated G1 arrest following transient inhibition of the mitotic spindle. J. Biol. Chem. 276(22): 19205-19213.
24. Courtman, D.W., Cho, A., Langille, L., and Wilson, G.J. 1998. Eliminating arterial pulsatile strain by external banding induces medial but not neointimal atrophy and apoptosis in the rabbit. Am. J. Pathol. 153: 1723-1729.
25. Cowan, K.M., Heilbut, A., Humpl, T., Lam, C., Ito, S., and Rabinovitch, M. 2000. Complete reversal of fatal pulmonary hypertension in rats by a serine elastase inhibitor. Nat. Med. 6: 698-702.
26. deBlois, D., and Marceau, F. 1987. The ability of des-Arg9-bradykinin to relax rabbit isolated mesenteric arteries is acquired during in vitro incubation. Eur. J. Pharmacol. 142: 141-144.
27. 9-bradykinin or of alpha-thrombin in rabbit aortic rings. Br. J. Pharmacol. 105: 959-967.
28. deBlois, D., Tea, B.-S., Dam, T.-V., Tremblay, J., and Hamet, P. 1997. Smooth muscle cell apoptosis during vascular regression in spontaneously hypertensive rats. Hypertension, 29: 340-349.
29. deBlois, D., Moreau, P., Tea, B.S., Tremblay, J., and Hamet, P. 2000. Pharmacological regulation of cardiovascular apoptosis in vivo. In Apoptosis in health and disease. Edited by R.R. Ruffolo and F. Walsh. Harwood Academic Publishers, Reading, UK. pp. 125-148.
30. deBlois, D., Orlov, S.N., and Hamet, P. 2001. Apoptosis in cardiovascular remodeling - effect of medication. Cardiovasc. Drugs Ther. 15: 539-545.
31. Der Sarkissian, S., Marchand, E.L., Duguay, D., Hamet, P., and deBlois, D. 2003. Reversal of interstitial fibroblast hyperplasia via apoptosis in hypertensive rat heart with valsartan or enalapril. Cardiovasc. Res. 57: 775-783.
32. Devlin, A.M., Gordon, J.F., Davidson, A.O., Clark, J.S., Hamilton, C.A., Morton, J.J. et al. 1995. The effects of perindopril on vascular smooth muscle polyploidy in stroke-prone spontaneously hypertensive rats. J. Hypertens. 13: 211-218.
33. Devlin, A.M., Clark, J.S., Reid, J.L., and Dominiczak, A.F. 2000. DNA synthesis and apoptosis in smooth muscle cells from a model of genetic hypertension [in process citation]. Hypertension, 36: 110-115.
34. Diez, J., Panizo, A., Hernandez, M., and Pardo, J. 1997a. Is the regulation of apoptosis altered in smooth muscle cells of adult spontaneously hypertensive rats? Hypertension, 29: 776-780.
35. Diez, J., Panizo, A., Hernandez, M., Vega, F., Sola, I., Fortuno, M.A., and Pardo, J. 1997b. Cardiomyocyte apoptosis and cardiac angiotensin-converting enzyme in spontaneously hypertensive rats. Hypertension, 30: 1029-1034.
36. Dimmeler, S., Rippmann, V., Weiland, U., Haendeler, J., and Zeiher, A.M. 1997. Angiotensin II induces apoptosis of human endothelial cells. Protective effect of nitric oxide. Circ. Res. 81: 970-976.
37. Dixon, B.S., and Dennis, M.J. 1997. Regulation of mitogenesis by kinins in arterial smooth muscle cells. Am. J. Physiol. 273(Pt. 1): C7-C20.
38. Dominiczak, A.F., Devlin, A.M., Lee, W.K., Anderson, N.H., Bohr, D.F., and Reid, J.L. 1996. Vascular smooth muscle polyploidy and cardiac hypertrophy in genetic hypertension. Hypertension, 27: 752-759.
39. Duchene, J., Schanstra, J.P., Pecher, C., Pizard, A., Susini, C., Esteve, J.P. et al. 2002. A novel protein-protein interaction between a G protein-coupled receptor and the phosphatase SHP-2 is involved in bradykinin-induced inhibition of cell proliferation. J. Biol. Chem. 277(43): 40375-40383.
40. Duguay, D., Sarkissian, S.D., Kouz, R., Ongali, B., Couture, R., and deBlois, D. 2004. Kinin B2 receptor is not involved in enalapril-induced apoptosis and regression of hypertrophy in spontaneously hypertensive rat aorta: possible role of B1 receptor. Br. J. Pharmacol. 141: 728-736.
41. Eakin, G.S., and Behringer, R.R. 2003. Tetraploid development in the mouse. Dev. Dyn. 228: 751-766.
42. Elhendy, A., Modesto, K.M., Mahoney, D.W., Khandheria, B.K., Seward, J.B., and Pellikka, P.A. 2003. Prediction of mortality in patients with left ventricular hypertrophy by clinical, exercise stress, and echocardiographic data. J. Am. Coll. Cardiol. 41: 129-135.
43. Fleischmann, E.H., and Schmieder, R.E. 2002. Are all antihypertensive drug classes equal in reducing left ventricular hypertrophy? Curr. Cardiol. Rep. 4: 474-478.
44. Fortuno, M.A., Ravassa, S., Etayo, J.C., and Diez, J. 1998. Overexpression of Bax protein and enhanced apoptosis in the left ventricle of spontaneously hypertensive rats: effects of AT1 blockade with losartan. Hypertension, 32: 280-286.
45. Fouty, B.W., and Rodman, D.M. 2003. Mevastatin can cause G1 arrest and induce apoptosis in pulmonary artery smooth muscle cells through a p27Kip1-independent pathway. Circ. Res. 92: 501-509.
46. Gallinat, S., Busche, S., Schutze, S., Kronke, M., and Unger, T. 1999. AT2 receptor stimulation induces generation of ceramides in PC12W cells. FEBS Lett. 443: 75-79.
47. Gonzalez, A., Lopez, B., Ravassa, S., Querejeta, R., Larman, M., Diez, J., and Fortuno, M.A. 2002. Stimulation of cardiac apoptosis in essential hypertension: potential role of angiotensin II. Hypertension, 39: 75-80.
48. Hale, T.M., Shoichet, M.J., Bushfield, T.L., and Adams, M.A. 2003. Time course of vascular structural changes during and after short-term antihypertensive treatment. Hypertension, 42: 171-176.
49. Hamet, P., Richard, L., Dam, T.-V., Teiger, E., Orlov, S.N., Gaboury, L. et al. 1995. Apoptosis in target organs of hypertension. Hypertension, 26: 642-648.
50. Hamet, P., Moreau, P., Dam, T.-V., Orlov, S.N., Tea, B.-S., deBlois, D., and Tremblay, J. 1996. The time window of apoptosis: a new component in the therapeutic strategy for cardiovascular remodeling. J. Hypertens. 14(Suppl. 5): S65-S70.
51. Haunstetter, A., and Izumo, S. 1998. Apoptosis: basic mechanisms and implications for cardiovascular disease. Circ. Res. 82: 1111-1129.
52. Hixon, M.L., Muro-Cacho, C., Wagner, M.W., Obejero-Paz, C., Millie, E., Fujio, Y. et al. 2000a. Akt1/PKB upregulation leads to vascular smooth muscle cell hypertrophy and polyploidization. J. Clin. Invest. 106: 1011-1020.
53. Hixon, M.L., Obejero-Paz, C., Muro-Cacho, C., Wagner, M.W., Millie, E., Nagy, J. 2000b. Cks1 mediates vascular smooth muscle cell polyploidization. J. Biol. Chem. 275(51): 40434-40442.
54. Holm, A.M., Andersen, C.B., Haunso, S., and Hansen, P.R. 2000. ACE-inhibition promotes apoptosis after balloon injury of rat carotid arteries. Cardiovasc. Res. 45: 777-782.
55. Horiuchi, M., Akishita, M., and Dzau, V.J. 1999. Recent progress in angiotensin II type 2 receptor research in the cardiovascular system. Hypertension, 33: 613-621.
56. Ichihara, S., Senbonmatsu, T., Price, E., Jr., Ichiki, T., Gaffney, F.A., and Inagami, T. 2001. Angiotensin II type 2 receptor is essential for left ventricular hypertrophy and cardiac fibrosis in chronic angiotensin II-induced hypertension. Circulation, 104: 346-351.
57. Intengan, H.D., and Schiffrin, E.L. 2001. Vascular remodeling in hypertension: roles of apoptosis, inflammation, and fibrosis. Hypertension, 38(Pt. 2): 581-587.
58. Iyer, S.N., Chappell, M.C., Averill, D.B., Diz, D.I., and Ferrario, C.M. 1998. Vasodepressor actions of angiotensin-(1-7) unmasked during combined treatment with lisinopril and losartan. Hypertension, 31: 699-705.
59. Izzard, T.D., Taylor, C., Birkett, S.D., Jackson, C.L., and Newby, A.C. 2002. Mechanisms underlying maintenance of smooth muscle cell quiescence in rat aorta: role of the cyclin dependent kinases and their inhibitors. Cardiovasc. Res. 53: 242-252.
60. Jugdutt, B.I., and Balghith, M. 2001. Enhanced regional AT(2)-receptor and PKC(epsilon) expression during cardioprotection induced by AT(1)-receptor blockade after reperfused myocardial infarction. J. Renin-Angiotensin- Aldosterone Syst. 2: 134-140.
61. Kjeldsen, S.E., Dahlof, B., Devereux, R.B., Julius, S., Aurup, P., Edelman, J. et al. 2002. Effects of losartan on cardiovascular morbidity and mortality in patients with isolated systolic hypertension and left ventricular hypertrophy: a Losartan Intervention for Endpoint Reduction (LIFE) substudy. JAMA, 288: 1491-1498.
62. Kleine, L., Liu, G., Leblanc, N., and Hebert, R.L. 2002. Bradykinin stimulates ceramide production by activating specific BK-B(1) receptor in rat small artery. Am. J. Physiol. Heart Circ. Physiol. 282: H175-H183.
63. Klett, C.P., Palmer, A., Gallagher, A.M., Rioseco-Camacho, N., and Printz, M.P. 1995. Differences in cultured cardiac fibroblast populations isolated from SHR and WKY rats. Clin. Exp. Pharmacol. Physiol. 22(Suppl. 1): S265-S267.
64. Kunjathoor, V.V., Chiu, D.S., O'Brien, K.D., and LeBoeuf, R.C. 2002. Accumulation of biglycan and perlecan, but not versican, in lesions of murine models of atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 22: 462-468.
65. Kurisu, S., Ozono, R., Oshima, T., Kambe, M., Ishida, T., Sugino, H. et al. 2003. Cardiac angiotensin II type 2 receptor activates the kinin/NO system and inhibits fibrosis. Hypertension, 41: 99-107.
66. Lage, J.M., Leamon, J.H., Pejovic, T., Hamann, S., Lacey, M., Dillon, D. et al. 2003. Whole genome analysis of genetic alterations in small DNA samples using hyperbranched strand displacement amplification and array-CGH. Genome Res. 13: 294-307.
67. Lanni, J.S., and Jacks, T. 1998. Characterization of the p53-dependent postmitotic checkpoint following spindle disruption. Mol. Cell. Biol. 18: 1055-1064.
68. Laurent, S., Boutouyrie, P., Asmar, R., Gautier, I., Laloux, B., Guize, L. et al. 2001. Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients. Hypertension, 37: 1236-1241.
69. Lee, R.M., Conyers, R.B., and Kwan, C.Y. 1992a. Incidence of multinucleated and polyploid aortic smooth muscle cells cultured from different age groups of spontaneously hypertensive rats. Can. J. Physiol. Pharmacol. 70: 1496-1501.
70. Lee, R.M., Tsoporis, J., and Wang, R.R. 1992b. Influence of chronic nadolol treatment on blood pressure and vascular changes in spontaneously hypertensive rats. Can. J. Physiol. Pharmacol. 70: 1261-1270.
71. Lemay, J., Hamet, P., and deBlois, D. 2000. Losartan-induced apoptosis as a novel mechanism for the prevention of vascular lesion formation after vascular injury. J. Renin-Angiotensin-Aldosterone Syst. 1: 39-42.
72. Lemay, J., Tea, B.S., Hamet, P., and deBlois, D. 2001. Regression of neointimal lesion in the carotid artery of nifedipine-treated SHR and WKY rats: possible role of apoptosis. J. Vasc. Res. 38: 462-470.
73. Levy, B.I., Benessiano, J., Henrion, D., Caputo, L., Heymes, C., Duriez, M. et al. 1996. Chronic blockade of AT2-subtype receptors prevents the effect of angiotensin II on the rat vascular structure. J. Clin. Invest. 98: 418-425.
74. Li, J.S., Touyz, R.M., and Schiffrin, E.L. 1998. Effects of AT1 and AT2 angiotensin receptor antagonists in angiotensin II-infused rats. Hypertension, 31(Pt. 2): 487-492.
75. Li, W., Ye, Y., Fu, B., Wang, J., Yu, L., Ichiki, T. et al. 1998. Genetic deletion of AT2 receptor antagonizes angiotensin II-induced apoptosis in fibroblasts of the mouse embryo. Biochem. Biophys. Res. Commun. 250: 72-76.
76. Liu, J.J., Peng, L., Bradley, C.J., Zulli, A., Shen, J., and Buxton, B.F. 2000. Increased apoptosis in the heart of genetic hypertension, associated with increased fibroblasts. Cardiovasc. Res. 45: 729-735.
77. Lombardi, D.M., Owens, G.K., and Schwartz, S.M. 1989. Ploidy in mesenteric vessels of aged spontaneously hypertensive and Wistar-Kyoto rats. Hypertension, 13: 475-479.
78. Marchand, E.L., Der Sarkissian, S., Hamet, P., and deBlois, D. 2003. Caspase-dependent cell death mediates the early phase of aortic hypertrophy regression in losartan-treated spontaneously hypertensive rats. Circ. Res. 92: 777-784.
79. Matsubara, H. 1998. Pathophysiological role of angiotensin II type 2 receptor in cardiovascular and renal diseases. Circ. Res. 83: 1182-1191.
80. Miura, S., and Karnik, S.S. 2000. Ligand-independent signals from angiotensin II type 2 receptor induce apoptosis. EMBO J. 19(15): 4026-4035.
81. Moreau, P., Tea, B.S., Dam, T.V., and Hamet, P. 1997. Altered balance between cell replication and apoptosis in hearts and kidneys of newborn SHR. Hypertension, 30: 720-724.
82. Moudgil, R., Musat-Marcu, S., Xu, Y., Kumar, D., and Jugdutt, B.I. 2002. Increased AT2R protein expression but not increased apoptosis during cardioprotection induced by AT1R blockade. Can. J. Cardiol. 18: 873-883.
83. Mulvany, M.J. 2002. Small artery remodeling and significance in the development of hypertension. News Physiol. Sci. 17: 105-109.
84. Nakajima, M., Hutchinson, H.G., Fujinaga, M., Hayashida, W., Morishita, R., Zhang, L. et al. 1995. The angiotensin II type 2 (AT2) receptor antagonizes the growth effects of the AT1 receptor: gain-of-function study using gene transfer. Proc. Natl. Acad. Sci. USA, 92: 10663-10667.
85. Nishimura, T., Vaszar, L.T., Faul, J.L., Zhao, G., Berry, G.J., Shi, L. et al. 2003. Simvastatin rescues rats from fatal pulmonary hypertension by inducing apoptosis of neointimal smooth muscle cells. Circulation, 2003: 1640-1645.
86. Nouet, I., and Nahmias, I. 2000. Signal transduction from the angiotensin II AT2 receptor. Trends Endocrinol. Metab. 11: 1-6.
87. Obeid, L.M., and Hannun, Y.A. 1995. Ceramide: a stress signal and mediator of growth suppression and apoptosis. J. Cell. Biochem. 58: 191-198.
88. Oda, O., Shinzato, T., Ohbayashi, K., Takai, I., Kunimatsu, M., Maeda, K., and Yamanaka, N. 1996. Purification and characterization of perlecan fragment in urine of end-stage renal failure patients. Clin. Chim. Acta, 255: 119-132.
89. Oishi, Y., Ozono, R., Yano, Y., Teranishi, Y., Akishita, M., Horiuchi, M. et al. 2003. Cardioprotective role of AT2 receptor in postinfarction left ventricular remodeling. Hypertension, 41(Pt. 2): 814-818.
90. Opie, L.H., and Sack, M.N. 2001. Enhanced angiotensin II activity in heart failure: reevaluation of the counterregulatory hypothesis of receptor subtypes. Circ. Res. 88: 654-658.
91. + ratio blocks apoptosis in vascular smooth muscle at a site upstream of caspase-3. J. Biol. Chem. 274(23): 16545-16552.
92. Otsuka, S., Sugano, M., Makino, N., Sawada, S., Hata, T., and Niho, Y. 1998. Interaction of mRNAs for angiotensin II type 1 and type 2 receptors to vascular remodeling in spontaneously hypertensive rats. Hypertension, 32: 467-472.
93. Owens, G.K. 1985. Differential effects of antihypertensive drug therapy on vascular smooth muscle cell hypertrophy, hyperploidy, and hyperplasia in the spontaneously hypertensive rat. Circ. Res. 56: 525-536.
94. Owens, G.K., and Schwartz, S.M. 1982. Alterations in vascular smooth muscle mass in the spontaneously hypertensive rat. Role in cellular hypertrophy, hyperploidy, and hyperplasia. Circ. Res. 51: 280-289.
95. Poteri, E., Rizzoni, D., Mulvany, M.J., De Ciuceis, C., Sleiman, I., Boari, G.E. et al. 2003. Adrenergic mechanisms and remodeling of subcutaneous small resistance arteries in humans. J. Hypertens. 21(12): 2344-2352.
96. Ragolia, L., Palaia, T., Paric, E., and Maesaka, J.K. 2003. Prostaglandin D2 synthase inhibits the exaggerated growth phenotype of spontaneously hypertensive rat vascular smooth muscle cells. J. Biol. Chem. 278(24): 22175-22181.
97. Ravassa, S., Fortuno, M.A., Gonzalez, A., Lopez, B., Zalba, G., Fortuno, A., and Diez, J. 2000. Mechanisms of increased susceptibility to angiotensin II-induced apoptosis in ventricular cardiomyocytes of spontaneously hypertensive rats. Hypertension, 36: 1065-1071.
98. Raymond, M.A., Desormeaux, A., Laplante, P., Vigneault, N., Filep, J.G., Landry, K. et al. 2004. Apoptosis of endothelial cells triggers a caspase-dependent anti-apoptotic paracrine loop active on vascular smooth muscle cells. FASEB J. 18(6): 705-707.
99. Reilly, D.F., Gordon, D., and Schwartz, S.M. 1988. Determination and comparison of the aortic polyploid smooth muscle content of human hypertensive subjects and normotensive controls. Acta Physiol. Scand. 133(Suppl. 571): 181-188.
100. + channels: an essential pathway in programmed cell death. Am. J. Physiol. Lung Cell. Mol. Physiol. 286: L49-L67.
101. Rizzoni, D., Rodella, L., Porteri, E., Rezzani, R., Guelfi, D., Piccoli, A. et al. 2000. Time course of apoptosis in small resistance arteries of spontaneously hypertensive rats. J. Hypertens. 18: 885-891.
102. Schanstra, J.P., Neau, E., Drogoz, P., Arevalo Gomez, M.A., Lopez Novoa, J.M., Calise, D. et al. 2002. In vivo bradykinin B2 receptor activation reduces renal fibrosis. J. Clin. Invest. 110: 371-379.
103. Schwartz, S.M., deBlois, D., and O'Brien, E.R. 1995. The intima. Soil for athrosclerosis and restenosis. Circ. Res. 77: 445-465.
104. Senbonmatsu, T., Ichihara, S., Price, E., Jr., Gaffney, F.A., and Inagami, T. 2000. Evidence for angiotensin II type 2 receptor-mediated cardiac myocyte enlargement during in vivo pressure overload. J. Clin. Invest. 106: R25-R29.
105. Sharifi, A.M., and Schiffrin, E.L. 1997. Apoptosis in aorta of deoxycorticosterone acetate-salt hypertensive rats: effect of endothelin receptor antagonism. J. Hypertens. 15: 1441-1448.
106. Sharifi, A.M., and Schiffrin, E.L. 1998. Apoptosis in vasculature of spontaneously hypertensive rats: effect of an angiotensin converting enzyme inhibitor and a calcium channel antagonist. Am. J. Hypertens. 11: 1108-1116.
107. Silke, J., and Vaux, D.L. 1998. Cell death: shadow baxing. Curr. Biol. 8(15): R528-R531.
108. Slowik, M.R., De Luca, L.G., Min, W., and Pober, J.S. 1996. Ceramide is not a signal for tumor necrosis factor-induced gene expression but does cause programmed cell death in human vascular endothelial cells. Circ. Res. 79: 736-747.
109. Smallegange, C., Hale, T.M., Bushfield, T.L., and Adams, M.A. 2004. Persistent lowering of pressure by transplanting kidneys from adult spontaneously hypertensive rats treated with brief antihypertensive therapy. Hypertension, 44: 89-94.
110. Stack, A.G., and Saran, R. 2002. Clinical correlates and mortality impact of left ventricular hypertrophy among new ESRD patients in the United States. Am. J. Kidney Dis. 40: 1202-1210.
111. Stoll, M., and Unger, T. 2001. Angiotensin and its AT2 receptor: new insights into an old system. Regul. Pept. 99(2-3): 175-182.
112. Storchova, Z., and Pellman, D. 2004. From polyploidy to aneuploidy, genome instability and cancer. Nat. Rev. Mol. Cell. Biol. 5: 45-54.
113. Strauer, B.E., and Schwartzkopff, B. 1998. Objectives of high blood pressure treatment: left ventricular hypertrophy, diastolic function, and coronary reserve. Am. J. Hypertens. 11: 879-881.
114. Stroth, U., and Unger, T. 1999. The renin-angiotensin system and its receptors. J. Cardiovasc. Pharmacol. 33(Suppl. 1): S21-S28; discussion S41-S43.
115. Taurin, S., Dulin, N.O., Pchejetski, D., Grygorczyk, R., Tremblay, J., Hamet, P., and Orlov, S.N. 2002a. c-Fos expression in ouabain-treated vascular smooth muscle cells from rat aorta: evidence for an intracellular-sodium- mediated, calcium-independent mechanism. J. Physiol. 543(Pt. 3): 835-847.
116. i ratio in cultured vascular smooth muscle cells. Circ. Res. 91: 915-922.
117. Tea, B.S., Dam, T.V., Moreau, P., Hamet, P., and deBlois, D. 1999. Apoptosis during regression of cardiac hypertrophy in spontaneously hypertensive rats: temporal regulation and spatial heterogeneity. Hypertension, 34: 229-235.
118. Tea, B.S., Der Sarkissian, S., Touyz, R.M., Hamet, P., and deBlois, D. 2000. Proapoptotic and growth-inhibitory role of angiotensin II type 2 receptor in vascular smooth muscle cells of spontaneously hypertensive rats in vivo. Hypertension, 35: 1069-1073.
119. Teiger, E., Dam, T.V., Richard, L., Wisnewsky, C., Tea, B.S., Gaboury, L. et al. 1996. Apoptosis in pressure overload-induced heart hypertrophy in the rat. J. Clin. Invest. 97: 2891-2897.
120. Thompson, C.B. 1995. Apoptosis in the pathogenesis and treatment of disease. Science (Wash., DC), 267: 1456-1462.
121. Thorin-Trescases, N., deBlois, D., and Hamet, P. 2001. Evidence of an altered in vivo vascular cell turnover in spontaneously hypertensive rats and its modulation by long-term antihypertensive treatment. J. Cardiovasc. Pharmacol. 38: 764-774.
122. Timmermans, P.B.M.W.M., Wong, P.C., Chiu, A.T., Herblin, W.F., Benfield, P., Carini, D.J. et al. 1993. Angiotensin II receptors and angiotensin II receptor antagonists. Pharmacol. Rev. 45: 205-251.
123. 2+ modulation by angiotensin II and endothelin-1 in cardiomyocytes and fibroblasts from hypertrophied hearts of spontaneously hypertensive rats. Hypertension, 28: 797-805.
124. Turek, Z., Kubat, K., Kazda, S., Hoofd, L., and Rakusan, K. 1987. Improved myocardial capillarisation in spontaneously hypertensive rats treated with nifedipine. Cardiovasc. Res. 21: 725-729.
125. Vogt, M., and Strauer, B.E. 1995. Response of hypertensive left ventricular hypertrophy and coronary microvascular disease to calcium antagonists. Am. J. Cardiol. 76(13): 24D-30D.
126. Wahl, A.F., Donaldson, K.L., Fairchild, C., Lee, F.Y., Foster, S.A., Demers, G.W., and Galloway, D.A. 1996. Loss of normal p53 function confers sensitization to Taxol by increasing G2/M arrest and apoptosis. Nat. Med. 2: 72-79.
127. Walter, S.V., and Hamet, P. 1986. Enhanced DNA synthesis in heart and kidney of newborn spontaneously hypertensive rats. Hypertension, 8: 520-525.
128. Werstiuk, E.S., and Lee, R.M. 2000. Vascular beta-adrenoceptor function in hypertension and in ageing. Can. J. Physiol. Pharmacol. 78: 433-452.
129. Wolter, K.G., Hsu, Y.T., Smith, C.L., Nechushtan, A., Xi, X.G., and Youle, R.J. 1997. Movement of Bax from the cytosol to mitochondria during apoptosis. J. Cell Biol. 139: 1281-1292.
130. Woolard, J., Hale, T.M., Bushfield, T.L., and Adams, M.A. 2003. Persistent lowering of arterial pressure after continuous and intermittent therapy. J. Hypertens. 21: 813-820.
131. Xu, Y., Menon, V., and Jugdutt, B.I. 2000. Cardioprotection after angiotensin II type 1 blockade involves angiotensin II type 2 receptor expression and activation of protein kinase C-epsilon in acutely reperfused myocardial infarction in the dog. Effect of UP269-6 and losartan on AT1- and AT2-receptor expression and IP3 receptor and PKCepsilon proteins. J. Renin-Angiotensin-Aldosterone Syst. 1: 184-195.