growth has support from in vitro studies. Work from our lab has documented that cyclic stretch of cardiomyocytes causes upregulation of VEGF and possibly other angiogenic factors; conditioned media from these stretched cells stimulates endothelial cells to proliferate, migrate and form tubes.128 Furthermore, stretch of coronary endothelial cells enhances tie-1, tie-2 and Flk-1.129 Volume overload is characterized by increased diastolic dimensions, which necessarily cause stretch of the ventricular cardiomyocytes and vasculature. As documented in this review and illustrated in Fig. 2B, this model of hypertrophy is associated with angiogenesis and arteriogenesis.

Hemodynamic forces not only play a role in the formation of microvessels, but are known to affect remodeling of larger vessels (reviewed in Ref. 130). High flow is known to drive endothelial cell proliferation in arterial remodeling.131 For example, Kassab and colleagues documented an increased luminal diameter in the right coronary artery in pigs with right ventricular hypertrophy induced by pulmonary hypertension.132

11. Summary

The development and persistence of cardiac hypertrophy may or may not include compensatory growth of the coronary vasculature. Ideally, growth occurs at two levels, i.e. there is a numerical increase in both arterioles and capillaries. The former maintains adequate maximal coronary perfusion, while the latter prevents expansion of capillary domains and diffusion distance for O2. It is obvious that angiogenesis and arteriogenesis are not linked to cardiac hypertrophy, but are generally model specific. Therefore, one needs to consider stimuli that are activated along with the factors evoking myocardial growth. These include metabolic stimuli, such as hypoxia and mechanical stimuli, i.e. stretch, shear stress. Other factors that may modify angiogenesis and arteriogenesis include age, altered hemodynamic states that negatively impact on coronary vessels and the intensity of the stimulus. Learning more about the angiogenic and arteriogenic mechanism that can be activated in various types of cardiac hypertrophy can provide the basis for effective non-invasive therapies.

272 R. J. Tomanek & E. I. Dedkov

References

1.Olsson R, Bugni W (1986). Coronary Circulation (Raven Press, New York), Ch. 48, pp. 987–1037.

2.Tomanek RJ (1990). Response of the coronary vasculature to myocardial hypertrophy. J Am Coll Cardiol 15: 528–533.

3.Rakusan K (1999). Vascularization of the heart during normal and pathological growth. Coron Angiogenesis, Adv Oregan Biol 7: 129–153.

4.Alfaro A, Schaible TF, Malhotra A, Yipintsoi T, Scheuer J (1983). Impaired coronary flow and ventricular function in hearts of hypertensive rats. Cardiovasc Res 17: 553–561.

5.Wangler RD, Peters KG, Marcus ML, Tomanek RJ (1982). Effects of duration and severity of arterial hypertension and cardiac hypertrophy on coronary vasodilator reserve. Circ Res 51: 10–18.

6.Yamamoto J, Tsuchiya M, Saito M, Ikeda M (1985). Cardiac contractile and coronary flow reserves in deoxycorticosterone acetate-salt hypertensive rats.

Hypertension 7: 569–577.

7.Breisch EA, White FC, Bloor CM (1984). Myocardial characteristics of pressure overload hypertrophy. A structural and functional study. Lab Invest 51: 333–342.

8.Breisch EA, White FC, Nimmo LE, Bloor CM (1986). Cardiac vasculature and flow during pressure-overload hypertrophy. Am J Physiol 251: H1031–H1037.

9.Mueller TM, Marcus ML, Kerber RE, Young JA, Barnes RW, Abboud FM (1978). Effect of renal hypertension and left ventricular hypertrophy on the coronary circulation in dogs. Circ Res 42: 543–549.

10.Tomanek RJ, Palmer PJ, Peiffer GL, Schreiber KL, Eastham CL, Marcus ML (1986). Morphometry of canine coronary arteries, arterioles, and capillaries during hypertension and left ventricular hypertrophy. Circ Res 58: 38–46.

11.Harrison DG, Marcus ML, Dellsperger KC, Lamping KG, Tomanek RJ (1991). Pathophysiology of myocardial perfusion in hypertension. Circulation 83: III14–III18.

12.Tomanek RJ, Davis JW, Anderson SC (1979). The effects of alpha-methyldopa on cardiac hypertrophy in spontaneously hypertensive rats: ultrastructural, stereological, and morphometric analysis. Cardiovasc Res 13: 173–182.

13.Tomanek RJ, Wangler RD, Bauer CA (1985).Prevention of coronary vasodilator reserve decrement in spontaneously hypertensive rats. Hypertension 7: 533–540.

14.Canby CA, Tomanek RJ (1989). Role of lowering arterial pressure on maximal coronary flow with and without regression of cardiac hypertrophy. Am J Physiol 257: H1110–H1118.

15.Ljungqvist A, Unge G (1973). The proliferative activity of the myocardial tissue in various forms of experimental cardiac hypertrophy. Acta Pathol Microbiol Scand [A] 81: 233–240.

16.Batra S, Rakusan K (1991). Geometry of capillary networks in volume overloaded rat heart. Microvasc Res 42: 39–50.

17.Tomanek RJ, Searls JC, Lachenbruch PA (1982). Quantitative changes in the capillary bed during developing, peak, and stabilized cardiac hypertrophy in the spontaneously hypertensive rat. Circ Res 51: 295–304.

18.Anversa P, Melissari M, Beghi C, Olivetti G (1984). Structural compensatory mechanisms in rat heart in early spontaneous hypertension. Am J Physiol 246: H739–H746.

19.Peters KG, Wangler RD, Tomanek RJ, Marcus ML (1984). Effects of long-term cardiac hypertrophy on coronary vasodilator reserve in SHR rats. Am J Cardiol 54: 1342–1348.

20.McAinsh AM, Geyer M, Fandrey J, Ruegg JC, Wiesner RJ (1998). Expression of vascular endothelial growth factor during the development of cardiac hypertrophy in spontaneously hypertensive rats. Mol Cell Biochem 187: 141–146.

21.Tomanek RJ, Schalk KA, Marcus ML, Harrison DG (1989). Coronary angiogenesis during long-term hypertension and left ventricular hypertrophy in dogs. Circ Res 65: 352–359.

22.Botham MJ, Lemmer JH, Gerren RA, Long RW, Behrendt DM, Gallagher KP (1984). Coronary vasodilator reserve in young dogs with moderate right ventricular hypertrophy. Ann Thorac Surg 38: 101–107.

23.Manohar M (1985). Transmural coronary vasodilator reserve, and flow distribution during tachycardia in conscious young swine with right ventricular hypertrophy. Cardiovasc Res 19: 104–112.

24.White FC, Nakatani Y, Nimmo L, Bloor CM (1992). Compensatory angiogenesis during progressive right ventricular hypertrophy. Am J Cardiovasc Pathol 4: 51–68.

25.Liu Z, Hilbelink DR, Gerdes AM (1991). Regional changes in hemodynamics and cardiac myocyte size in rats with aortocaval fistulas. 2. Long-term effects.

Circ Res 69: 59–65.

26.Chen Y, Torry RJ, Baumbach GL, Tomanek RJ (1994). Proportional arteriolar growth accompanies cardiac hypertrophy induced by volume overload. Am J Physiol 267: H2132–H2137.

27.Carabello BA, Nakano K, Corin W, Biederman R, Spann JF Jr (1989). Left ventricular function in experimental volume overload hypertrophy. Am J Physiol 256: H974–H981.

28.Olivetti G, Lagrasta C, Quaini F, Ricci R, Moccia G, Capasso JM, Anversa P (1989). Capillary growth in anemia-induced ventricular wall remodeling in the rat heart. Circ Res 65: 1182–1192.

29.Hultgren PB, Bove AA (1981). Myocardial blood flow and mechanics in volume overload-induced left ventricular hypertrophy in dogs. Cardiovasc Res 15: 522– 528.

30.Gascho JA, Mueller TM, Eastham C, Marcus ML (1982). Effect of volume overload hypertrophy on the coronary circulation awake dogs. Cardiovasc Res 16: 288–292.

31.Thomas DP, Phillips SJ, Bove AA (1984) Myocardial morphology and blood flow distribution in chronic volume overload hypertrophy in dogs. Basic Res Cardiol 79: 379–388.

274R. J. Tomanek & E. I. Dedkov

32.Badke FR, White FC, Le Winter M, Covell J, Andres J, Bloor C (1981). Effects of experimental volume overload hypertrophy on myocardial blood flow and cardiac function. Am J Physiol 241: H564–H570.

33.Bauman RP, Rembert JC Greenfield JC Jr (1998). Myocardial blood flow in awake dogs with chronic tricuspid regurgitation. Basic Res Cardiol 93: 63–69.

34.Doty DB, Wright CB, Hiratzka LF, Eastham CL, Marcus ML (1984). Coronary reserve in volume-induced right ventricular hypertrophy from atrial septal defect. Am J Cardiol 54: 1059–1063.

35.Harada K, Aoki M, Toyono M, Tamura M (2004). Coronary flow velocity and coronary flow velocity reserve in children with ventricular septal defect. Tohoku J Exp Med 202: 77–85.

36.Strauer BE (1992). The concept of coronary flow reserve. J Cardiovasc Pharmacol 19(Suppl 5): S67–S80.

37.Friberg P (1988). Diastolic characteristics and cardiac energetics of isolated hearts exposed to volume and pressure overload. Cardiovasc Rese 22: 329–339.

38.Tomanek RJ, Doty MK, Sandra A (1998). Early coronary angiogenesis in response to thyroxine: growth characteristics and upregulation of basic fibroblast growth factor. Circ Res 82: 587–593.

39.Tomanek RJ, Busch TL (1998) Coordinated capillary and myocardial growth in response to thyroxine treatment. Anat Rec 251: 44–49.

40.Gay RG, Raya TE, Lancaster LD, Lee RW, Morkin E, Goldman S (1988). Effects of thyroid state on venous compliance and left ventricular performance in rats.

Am J Physiol 254: H81–H88.

41.Chilian WM, Wangler RD, Peters KG, Tomanek RJ, Marcus ML (1985). Thyroxine-induced left ventricular hypertrophy in the rat. Anatomical and physiological evidence for angiogenesis. Circ Res 57: 591–598.

42.Wachtlova M, Ostadal B, Mares V (1985). Thyroxine-induced cardiomegaly in rats of different age. Physiol Bohemoslov 34: 385–394.

43.Breisch EA, White FC, Hammond HK, Flynn S, Bloor CM (1989). Myocardial characteristics of thyroxine stimulated hypertrophy. A structural and functional study. Basic Res Cardiol 84: 345–358.

44.Mall G, Zimmer G, Baden S, Mattfeldt T (1990). Capillary neoformation in the rat heart — stereological studies on papillary muscles in hypertrophy and physiologic growth. Basic Res Cardiol 85: 531–540.

45.Tomanek RJ, Connell PM, Butters CA, Torry RJ (1995). Compensated coronary microvascular growth in senescent rats with thyroxine-induced cardiac hypertrophy. Am J Physiol 268: H419–H425.

46.Heron MI, Kolar F, Papousek F, Rakusan K (1997). Early and late effect of neonatal hypoand hyperthyroidism on coronary capillary geometry and longterm heart function in rat. Cardiovasc Res 33: 230–240.

47.Heron MI, Rakusan K (1994). Geometry of coronary capillaries in hyperthyroid and hypothyroid rat heart. Am J Physiol 267: H1024–H1031.

48.Heron MI, Rakusan K (1996). Shortand long-term effects of neonatal hypoand hyperthyroidism on coronary arterioles in rat. Am J Physiol 271: H1746–H1754.

49.Craft-Cormney C, Hansen JT (1980). Early ultrastructural changes in the myocardium following thyroxine-induced hypertrophy. Virchows Arch B Cell Pathol Incl Mol Pathol 33: 267–273.

50.Klein I, Hong C (1986). Effects of thyroid hormone on cardiac size and myosin content of the heterotopically transplanted rat heart. J Clin Invest 77: 1694–1698.

51.Rongish BJ, Torry RJ, Tomanek RJ (1995). Coronary neovascularization of embryonic rat hearts cultured in oculo is independent of thyroid hormones. Am J Physiol 268: H811–H816.

52.Davies PF, Remuzzi A, Gordon EJ, Dewey CF Jr, Gimbrone MA Jr (1986). Turbulent fluid shear stress induces vascular endothelial cell turnover in vitro.

Proc Natl Acad Sci USA 83: 2114–2117.

53.Ziada AM, Hudlicka O, Tyler KR, Wright AJ (1984). The effect of long-term vasodilatation on capillary growth and performance in rabbit heart and skeletal muscle. Cardiovasc Res 18: 724–732.

54.Mall G, Schikora I, Mattfeldt T, Bodle R (1987). Dipyridamole-induced neoformation of capillaries in the rat heart. Quantitative stereological study on papillary muscles. Lab Invest 57: 86–93.

55.Torry RJ, O’Brien DM, Connell PM, Tomanek RJ (1992). Dipyridamoleinduced capillary growth in normal and hypertrophic hearts. Am J Physiol 262: H980–H986.

56.Fadel BM, Ellahham S, Ringel MD, Lindsay J Jr, Wartofsky L, Burman KD (2000). Hyperthyroid heart disease. Clin Cardiol 23: 402–408.

57.Turek Z, Grandtner M, Kreuzer F (1972). Cardiac hypertrophy, capillary and muscle fiber density, muscle fiber diameter, capillary radius and diffusion distance in the myocardium of growing rats adapted to a simulated altitude of 3500 m.

Pflugers Arch 335: 19–28.

58.Pietschmann M, Bartels H (1985). Cellular hyperplasia and hypertrophy, capillary proliferation and myoglobin concentration in the heart of newborn and adult rats at high altitude. Respir Physiol 59: 347–360.

59.Moravec M, Turek Z, Moravec J (2002). Persistence of neoangiogenesis and cardiomyocyte divisions in right ventricular myocardium of rats born and raised in hypoxic conditions. Basic Res Cardiol 97: 153–160.

60.Rakusan K, Turek Z, Kreuzer F (1981). Myocardial capillaries in guinea pigs native to high altitude (Junin, Peru, 4,105 m). Pflugers Arch 391: 22–24.

61.Lund DD, Tomanek RJ (1980). The effects of chronic hypoxia on the myocardial cell of normotensive and hypertensive rats. Anat Rec 196: 421–430.

62.Partovian C, Adnot S, Eddahibi S, Teiger E, Levame M, Dreyfus P, Raffestin B, Frelin C (1998). Heart and lung VEGF mRNA expression in rats with monocrotalineor hypoxia-induced pulmonary hypertension. Am J Physiol 275: H1948–H1956.

63.Ryan HE, Lo J, Johnson RS (1998). HIF-1 alpha is required for solid tumor formation and embryonic vascularization. EMBO J 17: 3005–3015.

64.Takagi H, King GL, Ferrara N, Aiello LP (1996). Hypoxia regulates vascular endothelial growth factor receptor KDR/Flk gene expression through adenosine A2 receptors in retinal capillary endothelial cells. Invest Ophthalmol Vis Sci 37: 1311–1321.

276R. J. Tomanek & E. I. Dedkov

65.William C, Koehne P, Jurgensen J, Grafe M, Wagner K, Bachmann S, Frei U, Eckardt K (2000). Tie2 receptor is stimulated by hypoxia and proinflammatory cytokines in human endothelial cells. Circ Res 87: 370.

66.Laughlin MH, McAllister RM (1992). Exercise training-induced coronary vascular adaptation. J Appl Physiol 73: 2209–2225.

67.Tomanek RJ (1994). Exercise-induced coronary angiogenesis: a review. Med Sci Sports Exerc 26: 1245–1251.

68.Brown M (2003). Exercise and coronary vascular remodeling in the healthy heart. Exp Physiol 88(5): 645–658.

69.Marcus KD, Tipton CM (1985). Exercise training and its effects with renal hypertensive rats. J Appl Physiol 59: 1410–1415.

70.Anversa P, Levicky V, Beghi C, McDonald SL, Kikkawa Y (1983). Morphometry of exercise-induced right ventricular hypertrophy in the rat. Circ Res 52: 57–64.

71.White FC, Witzel G, Breisch EA, Bloor CM, Nimmo LE (1988). Regional capillary and myocyte distribution in normal and exercise trained male and female rat hearts. Am J Cardiovasc Pathol 2: 247–253.

72.Mattfeldt T, Kramer KL, Zeitz R, Mall G (1986). Stereology of myocardial hypertrophy induced by physical exercise. Virchows Arch A Pathol Anat Histopathol 409: 473–484.

73.Buttrick PM, Levite HA, Schaible TF, Ciambrone G, Scheuer J (1985). Early increases in coronary vascular reserve in exercised rats are independent of cardiac hypertrophy. J Appl Physiol 59: 1861–1865.

74.Rakusan K, Wicker P (1990). Morphometry of the small arteries and arterioles in the rat heart: effects of chronic hypertension and exercise. Cardiovasc Res 24: 278–284.

75.Laughlin MH, Hale CC, Novela L, Gute D, Hamilton N, Ianuzzo CD (1991). Biochemical characterization of exercise-trained porcine myocardium. J Appl Physiol 71: 229–235.

76.Tittle K, Knacke K, Brauer B, Otto H (1966). Der Einfluss Korperlicker Belastengen Uterschiedlicker dauer und Intersitof auf die kapillarisierung der herzund skelettmuskulatur bei albino ratten. XVI Int World Congress Sports Medicine, pp. 181–188.

77.Loud AV, Beghi C, Olivetti G, Anversa P (1984). Morphometry of right and left ventricular myocardium after strenuous exercise in preconditioned rats. Lab Invest 51: 104–111.

78.Spear KL, Koerner JE, Terjung RL (1978). Coronary blood flow in physically trained rats. Cardiovasc Res 12: 135–143.

79.Mall G, Mattfeldt T, Hasslacher C, Mann J (1986). Morphological reaction patterns in experimental cardiac hypertrophy — a quantitative stereological study. Basic Res Cardiol 81(Suppl 1): 193–201.

80.Bloor CM, Leon AS (1970). Interaction of age and exercise on the heart and its blood supply. Lab Invest 22: 160–165.

81.Rakusan K, Ost’adal B, Wachtlova M (1971). The influence of muscular work on the capillary density in the heart and skeletal muscle of pigeon (Columbia livia dom.). Can J Physiol Pharmacol 49: 167–170.

82.White FC, McKirnan MD, Breisch EA, Guth BD, Liu YM, Bloor CM (1987). Adaptation of the left ventricle to exercise-induced hypertrophy. J Appl Physiol 62: 1097–1100.

83.Leon AS, Bloor CM (1968). Effects of exercise and its cessation on the heart and its blood supply. J Appl Physiol 24: 485–490.

84.Frenzel H, Schwartzkopff B, Holtermann W, Schnurch HG, Novi A, Hort W (1988). Regression of cardiac hypertrophy: morphometric and biochemical studies in rat heart after swimming training. J Mol Cell Cardiol 20: 737–751.

85.Laughlin MH, Overholser KA, Bhatte MJ (1989). Exercise training increases coronary transport reserve in miniature swine. J Appl Physiol 67: 1140–1149.

86.Norman TD, Coers CR (1960). Cardiac hypertrophy after coronary artery ligation in rats. Arch Pathol 69: 181–184.

87.Reiner L, Freudenthal RR, Suarez FH (1968). Cardiac weights of rats after experimental myocardial infarction. Arch Pathol 86: 465–474.

88.Rubin SA, Fishbein MC, Swan HJ (1983). Compensatory hypertrophy in the heart after myocardial infarction in the rat. J Am Coll Cardiol 1: 1435–1441.

89.Anversa P, Beghi C, Levicky V, McDonald SL, Kikkawa Y, Olivetti G (1985). Effects of strenuous exercise on the quantitative morphology of left ventricular myocardium in the rat. J Mol Cell Cardiol 17: 587-595.

90.Anversa P, Beghi C, Kikkawa Y, Olivetti G (1985). Myocardial response to infarction in the rat. Morphometric measurement of infarct size and myocyte cellular hypertrophy. Am J Pathol 118: 484–492.

91.Anversa P, Beghi C, Kikkawa Y, Olivetti G (1986). Myocardial infarction in rats. Infarct size, myocyte hypertrophy, and capillary growth. Circ Res 58: 26–37.

92.Anversa P, Capasso JM, Sonnenblick EH, Olivetti G (1990). Mechanisms of myocyte and capillary growth in the infarcted heart. Eur Heart J 11(Suppl B): 123–132.

93.Karam R, Healy BP, Wicker P (1990). Coronary reserve is depressed in postmyocardial infarction reactive cardiac hypertrophy. Circulation 81: 238–246.

94.Kozlovskis PL, Gerdes AM, Smets M, Moore JA, Bassett AL, Myerburg RJ (1991). Regional increase in isolated myocyte volume in chronic myocardial infarction in cats. J Mol Cell Cardiol 23: 1459–1466.

95.Olivetti G, Capasso JM, Meggs LG, Sonnenblick EH, Anversa P (1991). Cellular basis of chronic ventricular remodeling after myocardial infarction in rats. Circ Res 68: 856–869.

96.Xie Z, Gao M, Batra S, Koyama T (1997). The capillarity of left ventricular tissue of rats subjected to coronary artery occlusion. Cardiovasc Res 33: 671–676.

97.Van Kerckhoven R, Saxena PR, Schoemaker RG (2002). Restored capillary density in spared myocardium of infarcted rats improves ischemic tolerance. J Cardiovasc Pharmacol 40: 370–380.

98.Van Kerckhoven R, van Veghel R, Saxena PR, Schoemaker RG (2004). Pharmacological therapy can increase capillary density in post-infarction remodeled rat hearts. Cardiovasc Res 61: 620–629.

99.Kramer CM, Rogers WJ, Park CS, Seibel PS, Shaffer A, Theobald TM, Reichek N, Onodera T, Gerdes AM (1998). Regional myocyte hypertrophy parallels regional myocardial dysfunction during post-infarct remodeling. J Mol Cell Cardiol 30: 1773–1778.

278R. J. Tomanek & E. I. Dedkov

100.Zheng W, Weiss RM, Wang X, Zhou R, Arlen AM, Lei L, Lazartigues E, Tomanek RJ (2004). DITPA stimulates arteriolar growth and modifies myocardial postinfarction remodeling. Am J Physiol Heart Circ Physiol 286: H1994– H2000.

101.Dedkov EI, Christensen LP, Weiss RM, Tomanek RJ (2005). Reduction of heart rate by chronic beta1-adrenoceptor blockade promotes growth of arterioles and preserves coronary perfusion reserve in postinfarcted heart. Am J Physiol Heart Circ Physiol 288: H2684–H2693.

102.Turek Z, Grandtner M, Kubat K, Ringnalda BE, Kreuzer F (1978). Arterial blood gases, muscle fiber diameter and intercapillary distance in cardiac hypertrophy of rats with an old myocardial infarction. Pflugers Arch 376: 209–215.

103.Przyklenk K, Groom AC (1983) Microvascular evidence for a transition zone around a chronic myocardial infarct in the rat. Can J Physiol Pharmacol 61: 1516–1522.

104.Olivetti G, Ricci R, Beghi C, Guideri G, Anversa P (1986). Response of the border zone to myocardial infarction in rats. Am J Pathol 125: 476–483.

105.Kalkman EA, Bilgin YM, van Haren P, van Suylen RJ, Saxena PR, Schoemaker RG (1996). Determinants of coronary reserve in rats subjected to coronary artery ligation or aortic banding. Cardiovasc Res 32: 1088–1095.

106.Nelissen-Vrancken HJ, Debets JJ, Snoeckx LH, Daemen MJ, Smits JF (1996). Time-related normalization of maximal coronary flow in isolated perfused hearts of rats with myocardial infarction. Circulation 93: 349–355.

107.Kalkman EA, van Haren P, Saxena PR, Schoemaker RG (1997). Regionally different vascular response to vasoactive substances in the remodelled infarcted rat heart; aberrant vasculature in the infarct scar. J Mol Cell Cardiol 29: 1487–1497.

108.Gervais M, Richer C, Fornes P, De Gasparo M, Giudicelli JF (1999). Valsartan and coronary haemodynamics in early post-myocardial infarction in rats. Fundam Clin Pharmacol 13: 635–645.

109.Lei L, Zhou R, Zheng W, Christensen LP, Weiss RM, Tomanek RJ (2004). Bradycardia induces angiogenesis, increases coronary reserve, and preserves function of the postinfarcted heart. Circulation 110: 796–802.

110.Schieffer B, Wirger A, Meybrunn M, Seitz S, Holtz J, Riede UN, Drexler H (1994). Comparative effects of chronic angiotensin-converting enzyme inhibition and angiotensin II type 1 receptor blockade on cardiac remodeling after myocardial infarction in the rat. Circulation 89: 2273–2282.

111.Li J, Brown LF, Hibberd MG, Grossman JD, Morgan JP, Simons M (1996). VEGF, flk-1, and flt-1 expression in a rat myocardial infarction model of angiogenesis. Am J Physiol 270: H1803–H1811.

112.Jingjing L, Srinivasan B, Bian X, Downey HF, Roque RS (2000). Vascular endothelial growth factor is increased following coronary artery occlusion in the dog heart. Mol Cell Biochem 214: 23–30.

113.Kawata H, Yoshida K, Kawamoto A, Kurioka H, Takase E, Sasaki Y, Hatanaka K, Kobayashi M, Ueyama T, Hashimoto T, Dohi K (2001). Ischemic

preconditioning upregulates vascular endothelial growth factor mRNA expression and neovascularization via nuclear translocation of protein kinase C epsilon in the rat ischemic myocardium. Circ Res 88: 696–704.

114.Heba G, Krzeminski T, Porc M, Grzyb J, Ratajska A, Dembinska-Kiec A (2001). The time course of tumor necrosis factor-alpha, inducible nitric oxide synthase and vascular endothelial growth factor expression in an experimental model of chronic myocardial infarction in rats. J Vasc Res 38: 288–300.

115.Tomanek RJ (2005). Formation of the coronary vasculature during development.

Angiogenesis 8: 273–284.

116.Tomanek RJ, Hu N, Phan B, Clark EB (1999). Rate of coronary vascularization during embryonic chicken development is influenced by the rate of myocardial growth. Cardiovasc Res 41: 663–671.

117.Rakusan K, Flanagan MF, Geva T, Southern J, Van Praagh R (1992). Morphometry of human coronary capillaries during normal growth and the effect of age in left ventricular pressure overload hypertrophy. Circulation 86: 38–46.

118.Kolar F, Papousek F, Pelouch V, Ostadal B, Rakusan K (1998). Pressure overload induced in newborn rats: effects on left ventricular growth, morphology, and function. Pediatr Res 43: 521–526.

119.Crissman RP, Rittman B, Tomanek RJ (1985). Exercise-induced myocardial capillary growth in the spontaneously hypertensive rat. Microvasc Res 30: 185–194.

120.Unge G, Carlsson S, Ljungqvist A, Tornling G, Adolfsson J (1979). The proliferative activity of myocardial capillary wall cells in variously aged swimmingexercised rats. Acta Pathol Microbiol Scand [A] 87: 15–17.

121.Bache RJ, Alyono D, Sublett E, Dai XZ (1986). Myocardial blood flow in left ventricular hypertrophy developing in young and adult dogs. Am J Physiol 251: H949–H956.

122.Alyono D, Anderson RW, Parrish DG, Dai XZ, Bache RJ (1986). Alterations of myocardial blood flow associated with experimental canine left ventricular hypertrophy secondary to valvular aortic stenosis. Circ Res 58: 47–57.

123.Tomanek RJ, Gisolfi CV, Bauer CA, Palmer PJ (1988). Coronary vasodilator reserve, capillarity, and mitochondria in trained hypertensive rats. J Appl Physiol 64: 1179–1185.

124.Josko J, Mazurek M (2004). Transcription factors having impact on vascular endothelial growth factor (VEGF) gene expression in angiogenesis. Med Sci Monit 10: RA89–RA98.

125.Conway EM, Collen D, Carmeliet P (2001). Molecular mechanisms of blood vessel growth. Cardiovasc Res 49: 507–521.

126.Hudlicka O, Brown M (2000). Modulators of Angiogenesis: Hemodynamic Forces

(Marcel Dekker, New York).

127.Legault F, Rouleau JL, Juneau C, Rose C, Rakusan K (1990). Functional and morphological characteristics of compensated and decompensated cardiac hypertrophy in dogs with chronic infrarenal aorto-caval fistulas. Circ Res 66: 846–859.

128.Zheng W, Seftor EA, Meininger CJ, Hendrix MJ, Tomanek RJ (2001). Mechanisms of coronary angiogenesis in response to stretch: role of VEGF and TGFbeta. Am J Physiol Heart Circ Physiol 280: H909–H917.

280R. J. Tomanek & E. I. Dedkov

129.Zheng W, Christensen LP, Tomanek RJ (2004). Stretch induces upregulation of key tyrosine kinase receptors in microvascular endothelial cells. Am J Physiol 287: H2739–H2745.

130.Lehoux S, Tedgui A (1998). Signal transduction of mechanical stresses in the vascular wall. Hypertension 32: 338–345.

131.Sho E, Komatsu M, Sho M, Nanjo H, Singh TM, Xu C, Masuda H, Zarins CK (2003). High flow drives vascular endothelial cell proliferation during flowinduced arterial remodeling associated with the expression of vascular endothelial growth factor. Exp Mol Pathol 75: 1–11.

132.Kassab GS, Imoto K, White FC, Rider CA, Fung YC, Bloor CM (1993). Coronary arterial tree remodeling in right ventricular hypertrophy. Am J Physiol 265: H366–H375.