Cellular and Molecular Neurobiology

, Volume 19, Issue 5, pp 553–573

Angiotensin and Cerebral Blood Flow

  • Juan M. Saavedra
  • Yasuaki Nishimura
Article

Abstract

1.General properties of the cerebral circulation.

2.Cerebral blood flow autoregulation in hypertension, in stroke, and during the aging process.

3.The Angiotensin system.

4.Angiotensin receptor subtypes.

5.Angiotensin receptors and actions of Angiotensin II in the brain: interactions between the brain and circulating Angiotensin II.

6.The cerebrovascular Angiotensin system.

7.Effects of Angiotensin II on cerebrovascular reactivity.

8.Angiotensin and cerebrovascular flow.

9.Effects of therapeutic modulation of the Angiotensin II system on cerebrovascular regulation in health and disease.

10.Conclusions.

renin angiotensin system cerebral blood flow autoregulation stroke brain ischemia 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

REFERENCES

  1. Abboud, F. M. (1981). Special characteristics of the cerebral circulation. Fed. Proc. 40:2296–2300.Google Scholar
  2. Abdelwahab, W., Frishman, W., and Landau, A. (1995). Management of hypertensive urgencies and emergencies. J. Clin. Pharmacol. 35:747–762.Google Scholar
  3. Barry, D. I., Jarden, J. O., Paulson, O. B., Graham, D. I., and Strandgaard, S. (1984). Cerebrovascular aspects of converting-enzyme inhibition. I: Effects of intravenous captopril in spontaneously hypertensive and normotensive rats. J. Hypertens. 2:589–597.Google Scholar
  4. Baumbach, G. L., and Heistad, D. D. (1985). Regional, segmental and temporal heterogeneity of cerebral vascular autoregulation. Ann. Biomed. Eng. 13:303–310.Google Scholar
  5. Black, M. J., Adams, M. A., Bobik, A., Campbell, J. H., and Campbell, G. R. (1989). Effects of enalapril on aortic smooth muscle cell polyploidy in the spontaneously hypertensive rat. J. Hypertens. 7:997–1003.Google Scholar
  6. Brecher, P., Tercyak, A., and Chobanian, A. V. (1981). Properties of angiotensin-converting enzyme in intact cerebral micro vessels. Hypertension 3:198–204.Google Scholar
  7. Bray, L., Lartaud, I., Muller, F., et al. (1991). Effects of the angiotensin I converting enzyme inhibitor perindopril on cerebral blood flow in awake hypertensive rats. Am. J. Hypertens. 4:246S-252S.Google Scholar
  8. Brown, M. J., and Brown, J. (1986). Does angiotensin II protect against stroke? Lancet 2:427–429.Google Scholar
  9. Castrén, E., and Saavedra, J. M. (1988). Repeated stress increases the density of angiotensin II binding sites in rat paraventricular nucleus and subfornical organ. Endocrinology 122:370–372.Google Scholar
  10. Castrén, E., and Saavedra, J. M. (1989). Angiotensin II receptors in paraventricular nucleus, subfornical organ, and pituitary gland of hypophysectomized, adrenalectomized and vasopressin-deficient rats. Proc. Natl. Acad. Sci. USA 86:725–729.Google Scholar
  11. Dyker, A. G., Grosset, D. G., and Lees, K. (1997). Perindopril reduces blood pressure but not cerebral blood flow in patients with recent cerebral ischemic stroke. Stroke 28:580–583.Google Scholar
  12. Edvinsson, L., Hardebo, J.-E., and Owman, Ch. (1979). Effects of an giotensin II on cerebral blood vessels. Acta Physiol. Scand. 105:381–383.Google Scholar
  13. Edvinsson, L., MacKenzie, E. T., and McCulloch, J. (eds.) (1993). Cerebral Blood Flow and Metabolism, Raven Press, New York, pp. 1–683.Google Scholar
  14. Faraci, F. M., and Heistad, D. D. (1990). Regulation of large cerebral arteries and cerebral microvascular pressure. Circ. Res. 66:8–17.Google Scholar
  15. Fornes, P., Richer, C., Vacher, E., Bruneval, P., and Giudicelli, J. F. (1993). Losartan's protective effects in stroke-prone spontaneously hypertensive rats persist durably after treatment withdrawal. J. Cardiovasc. Pharm. 22:305–313.Google Scholar
  16. Frei, A., and Muller-Brand, J. (1986). Cerebral blood flow and antihypertensive treatment with enalapril. J. Hypertens. 4:365–367.Google Scholar
  17. Fujii, K., Weno, B. L., Baumbach, G. L., and Heistad, D. D. (1992). Effects of antihypertensive treatment on focal cerebral infarction. Hypertension 19:713–716.Google Scholar
  18. Gutkind, J. S., Kurihara, M., and Saavedra, J. M. (1988). Increased angiotensin II receptors in brain nuclei of DOCA-salt hypertensive rats. Am. J. Physiol. 255:H646-H650.Google Scholar
  19. Haas, D. C., Anderson, G. H, and Streeten, D. H. P. (1985). Role of angiotensin in lethal cerebral hypoperfusion during treatment of acute hypertension. Arch. Int. Med. 145:1922–1924.Google Scholar
  20. Haberl, R. L. (1994). Role of angiotensin receptor subtypes in the response of Rabbit brain arterioles to angiotensin. Stroke 25:1476–1480.Google Scholar
  21. Haberl, R. L., Anneser, F., Villringer, A., and Einhäupl, K. M. (1990). Angiotensin II induces endothelium-dependent vasodilation of rat cerebral arterioles. Am. J. Physiol. 258:H1840-H1846.Google Scholar
  22. Haberl, R. L., Decker, P. J., and Einhäupl, K. M. (1991). Angiotensin degradation products mediate endothelium-dependent dilation of rabbit brain arterioles. Circ. Res. 68:1621–1627.Google Scholar
  23. Haberl, R. L., Decker-Hermann, P. J., and Hermann, K. (1996). Effect of renin on brain arterioles and cerebral blood flow in rabbits. J. Cereb. Blood Flow Metab. 16:714–719.Google Scholar
  24. Hajdu, M. A., Heistad, D. D., Ghoneim, S., and Baumbach, G. F. (1991). Effects of antihypertensive treatment on composition of cerebral arterioles. Hypertension 18(Suppl. II):1115–1121.Google Scholar
  25. Hammersen, F., and Messmer, K. (eds.) (1990). Cerebral Microcirculation, Karger, Basel, pp. 1–102.Google Scholar
  26. Inada, Y., Wada, T., Ojima, M., Sanada, T., Shibouta, Y., Kanagawa, R., Ishimura, Y., Fijisawa, Y., and Nishikawa, K. (1997). Protective effects of Candesartan cilexetil (TCV-116) against stroke, kidney dysfunction and cardiac hypertrophy in stroke prone spontaneously hypertensive rats. Clin. Expr. Hypertens. 19:1079–1099.Google Scholar
  27. Inagami, T., Iwai, N., Sasaki, K., Guo, D.-F., Furuta, H., Yamano, Y., Bardhan, S., Chaki, S., Makito, N., and Badr, K. (1993). Angiotensin II receptors: Cloning and regulation. Arzneim-Forsch./Drug Res. 43:226–228.Google Scholar
  28. Inagami, T., Guo, D.-F., and Kitami, Y. (1994). Molecular biology of angiotensin II receptors: An overview. J. Hypertens. 12(Suppl. 10):S83-S94.Google Scholar
  29. Kamishirado, H., Inoue, T., Fujito, T., Kase, M., Shimizu, M., Sakai, Y., Takayanagi, K., Morroka, S., and Natsui, S. (1997). Effect of enalapril maleate on cerebral blood flow in patients with chronic heart failure. Angiology 48:707–713.Google Scholar
  30. Kimme, P., Gustafsson, U., Sollevi, A., Nilsson, G., and Sjoberg, F. (1997). Cerebral blood flow of the exposed brain surface measured by laser Doppler perfusion imaging. Acta Physiol. Scand. 159:15–22.Google Scholar
  31. Kobayashi, H., Take, K., Wada, A., Izumi, F., and Magnoni, M. S. (1984). Angiotensin-converting enzyme activity is reduced in brain microvessels of spontaneously hypertensive rats. J Neurochem. 42:1655–1658.Google Scholar
  32. Kobayashi, H., Wada, A., Izumi, F., Take, K., and Magnoni, M. S. (1985). Low activity of angiotensin-converting enzyme in cerebral microvessels of young spontaneously hypertensive rats. J. Neurochem. 44:1318–1320.Google Scholar
  33. Kobayashi, S., Yamaguchi, S., Okada, K., Suyama, N., Bokura, K., and Murao, M. (1992). The effect of enalapril maleate on cerebral blood flow in chronic infarction. Angiology 43:378–388.Google Scholar
  34. Kramar, E. A., Harding, J. W., and Wright, J. W. (1997). Angiotensin II-and IV-induced changes in cerebral blood flow. Roles of AT1, AT2, and AT4 receptor subtypes. Regul. Peptides 68:131–128.Google Scholar
  35. Krejcy, K., Wolzt, M., Kreuzer, C., Breitender, H., Schutz, W., Eichler, H. G., and Schmetterer, L. (1997). Characterization of angiotensin-II effects on cerebral and ocular circulation by noninvasive methods. Br. J. Clin. Pharmacol. 43:501–508.Google Scholar
  36. Lartaud, I., Makki, T., Bray-des-Boscs, L., Niederhoffer, N., Atkinson, J., Corman, B., and Capdeville-Atkinson, C. (1994). Effect of chronic Ang I-converting enzyme inhibition on aging processes. IV. Cerebral blood flow regulation. Am. J. Physiol. 267:R687-R694.Google Scholar
  37. Lees, K. R., and Dyker, A. G. (1996). Blood pressure control after acute stroke. J. Hypertens. Suppl. 14:S35-S38.Google Scholar
  38. Levy, B. I., and Safar, M. E. (1992). Remodelling of the vascular system in response to hypertension and drug therapy. Clin. Exp. Pharmacol. Physiol. 19:33–37.Google Scholar
  39. Maktabi, M. A., Heistad, D. D., and Faraci, F. M. (1990). Effects of angiotensin II on blood flow to choroid plexus. Am. J. Physiol. 258:H414-H418.Google Scholar
  40. Maktabi, M. A., Todd, M. M., and Stachovic, G. (1995). Angiotensin II contributes to cerebral vasodilation during hypoxia in the rabbit. Stroke 26:1871–1876.Google Scholar
  41. Manabe, K., Shirahase, H., Usui, H., Kurahashi, K., and Figiwara, M. (1989). Endothelium-dependent contractions induced by angiotensin I and angiotensin II in canine cerebral artery. J. Pharmacol. Exp. Ther. 251:317–320.Google Scholar
  42. Mayhan, W. G, Faraci, F. M, Baumbach, G. L, and Heistad, D. D. (1990). Effects of aging on responses of cerebral arterioles. Am. J. Physiol. 258:H1138-H1143.Google Scholar
  43. Mendelsohn, F. A. O., Quirion, R., Saavedra, J. M., Aguilera, G., and Catt, K. J. (1984). Autoradiographic localization of angiotensin II receptors in rat brain. Proc. Natl. Acad. Sci. USA 81:1575–1579.Google Scholar
  44. Moreau, P., Takase, H., Kung, C. F., van Rooijen, M. M., Schaffner, T., and Luscher, T. F. (1995). Structure and function of the rat basilar artery during chronic nitric oxide synthase inhibition. Stroke 26:1922–1928.Google Scholar
  45. Morrow, B. A., Keil, L. C., and Severs, W. B. (1992). Resistance of outflow of cerebrospinal fluid after central infusions of angiotensin. Proc. Soc. Exp. Biol. Med. 199:34–37.Google Scholar
  46. Mraovitch, S., and Sercombe, R. (1996). Neurophysiological Basis of Cerebral Blood Flow Control: An Introduction, John Libbey, London, pp. 1–408.Google Scholar
  47. Muller, F., Lartaud, I., Bray, L., et al. (1990). Chronic treatment with the angiotensin I converting enzyme inhibitor, perindopril, restores the lower limit of autoregulation of cerebral blood flow in the awake renovascular hypertensive rat. J. Hypertens. 8:1037–1042.Google Scholar
  48. Nag, S., and Kilty, D. W. (1997). Cerebrovascular changes in chronic hypertension. Protective effects of enalapril in rats. Stroke 28:1028–1034.Google Scholar
  49. Naritomi, H., Shimizu, T., Watanabe, Y., Murata, S., and Sawada, T. (1994). Effects of the angiotensin-converting enzyme inhibitor alacepril on cerebral blood flow in hypertensive stroke patients: A pilot study. Curr. Ther. Res. 55:1446–1454.Google Scholar
  50. Näveri, L., Strömberg, C., and Saavedra, J. M. (1994a). Angiotensin II AT2 receptor stimulation extends the upper limit of cerebral blood flow autoregulation: Agonist effects of CGP 42112 and PD 123319. J. Cereb. Blood Flow Metab. 14:38–44.Google Scholar
  51. Näveri, L., Strömberg, C., and Saavedra, J. M. (1994b). Angiotensin II AT1 receptor mediated contraction of the perfused rat cerebral artery. NeuroReport 5:2278–2280.Google Scholar
  52. Näveri, L., Strömberg, C., and Saavedra, J. M. (1994c). Angiotensin IV reverses the acute cerebral blood flow reduction after experimental subarachnoid hemorrhage in the rat. J. Cereb. Blood Flow Metab. 14:1096–1099.Google Scholar
  53. Nazarali, A. J., Gutkind, J. S., and Saavedra, J. M. (1989). Calibration of [125I]-polymer standards with [125I]-brain paste standards for use in quantitative receptor autoradiography. J. Neurosci. Methods 30:247–253.Google Scholar
  54. Nishimura, Y., Xu, T., Jöhren, O., Häuser, W., and Saavedra, J. M. (1998). The angiotensin AT1 receptor antagonist CV-11974 regulates cerebral blood flow and brain angiotensin AT1 receptor expression. Basic Res. Cardiol. Suppl. 2:63–68 (1998).Google Scholar
  55. Nobile-Orazio, E., and Sterzi, R. (1981). Cerebral ischemia after nifedipine treatment. Br. Med. J. 283:948.Google Scholar
  56. Olesen, J. (1972). The effect of intracarotid epinephrine, norepinephrine, and angiotensin on the regional cerebral blood flow in man. Neurology 22:978–987.Google Scholar
  57. Ooboshi, H., Sadoshima, S., Fujii, K., et al. (1990). Acute effects of antihypertensive agents on cerebral blood flow in hypertensive rats. Eur. J. Pharmacol. 179:253–261.Google Scholar
  58. Page, I. H. (1987). Hypertension Mechanisms, Grune & Startton, New York, pp. 1–1002.Google Scholar
  59. Palmer, R. M. J., Ferrige, A. G., and Moncada, S. (1987). Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 327:524–526.Google Scholar
  60. Paulson, O. B., and Waldemar, G. (1991). Role of the local renin-angiotensin system in the autoregulation of the cerebral circulation. Blood Vessels 28:231–235.Google Scholar
  61. Paulson, O. B., Waldemar, G., Andersen, A. R., Barry, D. I., Pedersen, E. V., Schmidt, J. F., and Vorstrup, S. (1988). Role of angiotensin in autoregulation of cerebral blood flow. Circulation 77(Suppl. I):155–158.Google Scholar
  62. Perich, R., Jackson, B., Paxton, D., and Johnston, C. (1992). Characterization of angiotensin converting enzyme in isolated cerebral microvessels from spontaneously hypertensive and normotensive rats. J. Hypertens. 10:149–153.Google Scholar
  63. Phillips, M. I., (1987). Functions of angiotensin in the central nervous system. Annu. Rev. Physiol. 49:413–435.Google Scholar
  64. Phillis, J. W. (1993). The Regulation of Cerebral Blood Flow, CRC Press, Boca Raton, FL, pp. 1–425.Google Scholar
  65. Postiglione, A., Bobkiewicz, T., Vinholdt-Pedersen, E., Lassen, N. A, Paulson, O. B., and Barry, D. I. (1991). Cerebrovascular effects of angiotensin converting enzyme inhibition involve large artery dilatation in rats. Stroke 22:1363–1368.Google Scholar
  66. Reis, D. J., and Iadecola, C. (1991). Intrinsic central neural regulation of cerebral blood flow and metabolism in relation to volume transmission. In Fuxe, K., and Agnati, L. F. (eds.) Volume Transmission in the Brain: Novel Mechanisms for Neural Transmission, Raven Press, New York, pp. 523–538.Google Scholar
  67. Reyneir-Rebufel, A.-M., Pinard, E., Aubineau, P.-F., Meric, P., and Seylaz, J. (1983). Generalized cerebral vasoconstriction induced by intracarotid infusion of angiotensin II in the rabbit. Brain Res. 269:91–101.Google Scholar
  68. Rosenblum, W. I., El-Sabban, F., and Hirsh, P. D. (1986). Angiotensin delays platelet aggregation after injury of cerebral arterioles. Stroke 17:1203–1205.Google Scholar
  69. Saavedra, J. M. (1992). Brain and pituitary angiotensin. Endocr. Rev. 13:329–380.Google Scholar
  70. Saavedra, J. M., and Timmermans, P. M. W. M. (1994). Angiotensin Receptors, Plenum Press, New York, pp. 1–413.Google Scholar
  71. Saavedra, J. M., Correa, F. M. A., Plunkett, L. M., Israel, A, Kurihara, M., and Shigematsu, K. (1986). Binding of angiotensin and atrial natriuretic peptide in brain of hypertensive rats. Nature 320:758–760.Google Scholar
  72. Sadoshima, S., Kenichiro, F., Ooboshi, H., Ibayashi, S., and Fujishima, M. (1993). Angiotensin converting enzyme inhibitors attenuate ischemic brain metabolism in hypertensive rats. Stroke 24:1561–1567.Google Scholar
  73. Sadoshima, S., Nagao, T., Ibayashi, S., and Fujishima, M. (1994). Inhibition of angiotensin-converting enzyme modulates the autoregulation of regional cerebral blood flow in hypertensive rats. Hypertension 23:781–785.Google Scholar
  74. Sandberg, K. (1994). Structural analysis and regulation of angiotensin II receptors. Trends Endoer. Metab. 5:28–35.Google Scholar
  75. Shigematsu, K., Saavedra, J. M., Plunkett, L. M., Kurihara, M., and Correa, F. M. A. (1986). Angiotensin II binding sites in the anteroventral-third ventricle (AV3V) area and related structures of the rat brain. Neurosci. Lett. 67:37–41.Google Scholar
  76. Shiota, N., Saegusa, Y., Nishimura, K., and Miyazaki, M. (1997). Angiotensin II-generating system in dog and monkey ocular tissues. Clin. Exp. Pharmacol. Physiol. 24:243–248.Google Scholar
  77. Speth, R. C., and Harik, S. I. (1985). Angiotensin II receptor binding sites in brain microvessels. Proc. Natl. Acad. Sci. USA 82:6340–6343.Google Scholar
  78. Squire, I. B. (1994). Actions of angiotensin II on cerebral blood flow autoregulation in health and disease. J. Hypertens. 12:1203–1208.Google Scholar
  79. Strandgaard, S., and Paulson, O. B. (1995). Cerebral blood flow in untreated and treated hypertension. Neth. J. Med. 47:180–184.Google Scholar
  80. Strömberg, C., Näveri, L., and Saavedra, J. M. (1992). Angiotensin AT2 receptors regulate cerebral blood flow in rats. Neuroreport 3:703–704.Google Scholar
  81. Suzuki, N., Sako, K., and Yonemasu, Y. (1991). Effects of induced hypertension on blood flow and capillary permeability in rats with experimental brain tumors. J. Neurooncol. 10:213–218.Google Scholar
  82. Takeyama, K., Minato, H., Nakatsuji, K., et al. (1986). Effect of the novel orally active angiotensin converting enzyme inhibitor alacepril on cardiovascular system in experimental animals. Arzneim-Forsch. Drug Res. 36:69–73.Google Scholar
  83. Tamaki, K., Saku, Y., and Ogata, J. (1992). Effects of angiotensin and atrial natriuretic peptide on the cerebral circulation. J. Cereb. Blood Flow Metab. 12:318–325.Google Scholar
  84. Timmermans, P. B. M. W. M., Carini, D. J., Chiu, A. T., Duncia, J. V., Price, W. A. Jr, Wells, G. J., Wong, P. C., Wexler, R. R., and Johnson, A. L. (1991). Angiotensin II receptor antagonists. From discovery to antihypertensive drugs. Hypertension 18,(Suppl. III):III-136-III-142.Google Scholar
  85. Timmermans, P. B. M. W. M., Inagami, T., Saavedra, J. M., Ardaillou, R., Rosenfeld, C. R., and Mendelsohn, F. A. O. (1995). Angiotensin receptor subtypes and their pharmacology. In Cuello, A. C., Collier, B. (eds.), Pharmacological Sciences: Perspectives for Research and Therapy in the Late 1990's, Birkhäuser Verlag, Basel, Switzerland, pp. 37–58.Google Scholar
  86. Toda, N. (1984). Endothelium-dependent relaxation induced by angiotensin II and histamine in isolated arteries of dog. Br. J. Pharmacol. 81:301–307.Google Scholar
  87. Toda, N., and Miyazaki, M. (1981). Angiotensin-induced relaxation in isolated dog renal and cerebral arteries. Am. J. Physiol. 240:H247-H254.Google Scholar
  88. Toda, N, Ayaziki, K., and Okamura, T. (1990). Modifications by endogenous prostaglandins of angiotensin II-induced contractions in dog and monkey cerebral and mesentric artiers. J. Pharmacol. Exp. Ther. 252:374–379.Google Scholar
  89. Tomura, N., Kato, T., Kanno, I., Shishido, F., Anugami, A., Uemura, K., Higano. S., Fujita, H., Mineura, K., and Kowada, M. (1993). Increased blood flow in human brain tumor after administration of angiotensin II: Demonstration by PET. Comput. Med. Imaging Graph. 17:443–439.Google Scholar
  90. Torup, M., Waldemar, G., and Paulson, O. B. (1993). Ceranapril and cerebral blood flow autoregulation. J. Hypertens. 1:399–405.Google Scholar
  91. Toyoda, K., Fujii, K., Ibayashi, S., Kitazono, T., Nagao, T., Takaba, H, and Fijishima, M. (1998). Attenuation and recovery of brain stem autoregulation in spontaneously hypertensive rats. J. Cereb. Blood Flow Metab. 18:305–310.Google Scholar
  92. Tsutsumi, K., and Saavedra, J. M. (1991a). Characterization and development of angiotensin-II receptor subtypes (AT1 and AT2) in rat brain. Am. J. Physiol. 261:R209-R216.Google Scholar
  93. Tsutsumi, K., and Saavedra, J. M. (1991b). Increased dithiothreitol-insensitive, type 2 angiotensin II receptors in selected brain areas of young rat. Cell. Mol. Neurobiol. 11:295–299.Google Scholar
  94. Tsutsumi, K., and Saavedra, J. M. (1991c). Quantitative autoradiography reveals different angiotensin II receptor subtypes in selected rat brain nuclei. J. Neurochem. 56:348–351.Google Scholar
  95. Tsutsumi, K., and Saavedra, J. M. (1991d). Differential development of angiotensin II receptor subtypes in the rat brain. Endocrinology 128:630–632.Google Scholar
  96. Tsutsumi, K., and Saavedra, J. M. (1991e). Characterization of AT2 angiotensin II receptors in rat anterior cerebral arteries. Am. J. Physiol. 261:H667-H670.Google Scholar
  97. Tuor, U. I., Kondysar, M. H., and Harding, R. K. (1988). Effect of angiotensin II and peptide YY on cerebral and circumventricular blood flow. Peptides 9:141–149.Google Scholar
  98. Veniant, M., Clozel, J. P., Kuhn, P., and Clozel, M. (1992). Protective effect of cilazapril on the cerebral circulation. J. Cardiovasc. Pharmacol. 19(Suppl. 6):S94-S99.Google Scholar
  99. Vraamak, T., Waldemar, G., Stradgaard, S., and Paulson, S., (1995). Angiotensin II receptor antagonist CV-11974 and cerebral blood flow autoregulation. J. Hypertens. 13:755–761.Google Scholar
  100. Wada, T., Kanagawa, R., Ishimura, Y., Inada, Y., and Nishikawa, K. (1995). Role of angiotensin II in cerebrovascular and renal damage in deoxyorticosterone acetate-salt hypertensive rats. J. Hypertens. 13:113–122.Google Scholar
  101. Waldemar, G., and Paulson, O. B. (1989). Angiotensin converting enzyme inhibition and cerebral circulation—A review. Br. J. Clin. Pharmacol. 28:177S-182S.Google Scholar
  102. Waldemar, G., Schmidt, J. F., Andersen, A. R., Vorstrup, S., Ibsen, H., and Paulson, O. B. (1989). Angiotensin converting enzyme inhibition and cerebral blood flow autoregulation in normotensive and hypertensive man. J. Hypertens. 7:229–235.Google Scholar
  103. Waldemar, G., Ibsen, H., Strandgaard, S., Andersen, A. R., Reasmissen, S., and Paulson, O. B. (1990). The effect of fosinopril sodium on cerebral blood flow in moderate essential hypertension. Am. J. Hypertens. 13:464–470.Google Scholar
  104. Wei, E. P., Kontos, H. A., and Patterson, J. L. (1978). Vasoconstrictor effect of angiotensin on pial arteries. Stroke 9:487–489.Google Scholar
  105. Welch, K. M. A., Caplan, L. R., Reis, D. J., Siesjö, and Weir, B. (eds.) (1997). Primer on Cerebrovascular Diseases, Academic Press, New York, pp. 1–823.Google Scholar
  106. Werner, C., Hoffman, W. E., Kochs, E., Rabito, S. F., and Miletich, D. J. (1991). Captopril improves neurologic outcome from incomplete cerebral isclemia in rats. Stroke 22:910–914.Google Scholar
  107. Werner, C., Kochs, E., Hoffman, W. E., Blanc, I. F., and Schulte am Esch, J. (1993). Cerebral blood flow and cerebral blood flow velocity during angiotensin-induced arterial hypertension in dogs. Can. J. Anesth. 40:755–760.Google Scholar
  108. Whalley, E. T., and Wahl, M. (1988). Cerebrovascular reactivity to angiotensin and angiotensin-converting enzyme activity in cerebrospinal fluid. Brain Res. 438:1–7.Google Scholar
  109. Winquist, R. J., and Bohr, D. F. (1983). Structural and functional changes in cerebral arteries from spontaneously hypertensive rats. Hypertension 5:292–297.Google Scholar
  110. Wright, J. W., and Harding, J. W. (1994). Brain angiotensin receptor subtypes in the control of physiological and behavioral responses. Neurosci. Biobehav. Rev. 18:21–53.Google Scholar

Copyright information

© Kluwer Academic/Plenum Publishers 1999

Authors and Affiliations

  • Juan M. Saavedra
    • 1
  • Yasuaki Nishimura
    • 1
  1. 1.Section on PharmacologyNational Institute of Mental HealthBethesda

Personalised recommendations