This Article Free Full Text (Free PDF) Free References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Ito, T. Articles by Saavedra, J. Search for Related Content PubMed PubMed Citation Articles by Ito, T. Articles by Saavedra, J. Social Bookmarking                   What's this?

Pre-treatment with candesartan protects from cerebral ischaemia

Section on Pharmacology, NIMH, NIH, Bethesda MD 20892, USA

Yasuaki Nishimura

Section on Pharmacology, NIMH, NIH, Bethesda MD 20892, USA

Juan Saavedra

Section on Pharmacology, NIMH, NIH, Bethesda MD 20892, USA, Saavedrj{at}irp.nimh.nih.gov

Angiotensin II (Ang II) regulates cerebral blood flow by stimulating cerebral vasoconstriction via AT₁receptors. In adult spontaneously hypertensive rats (SHR), the cerebrovascular autoregulatory curve is shifted to the right, in the direction of higher blood pressures, an indication of excessive cerebrovascular vasoconstriction. A restricted capacity to dilate cerebral blood vessels may be responsible for the enhanced vulnerability to cerebrovascular ischaemia during hypertension. We found that chronic treatment with the AT₁-receptor antagonist, candesartan, (0.5 mg/kg/day for 14 days, via osmotic minipumps implanted in the subcutaneous tissue) blocked Ang II binding to AT₁ -receptors in cerebral blood vessels and in brain areas involved in the regulation of cerebrovascular flow, and increased the ratio of lumen-wall area in the middle cerebral artery. Candesartan treatment normalised the lower part of the autoregulatory curve in SHR, and markedly decreased cerebral ischaemia as a consequence of middle cerebral artery occlusion with reperfusion. Protection from ischaemia is related to arterial remodelling, enhanced compensatory vasodilatation in the peripheral area of ischaemia, decreased reduction in cerebral blood flow following the occlusion of a major cerebral blood vessel, and protection from injury in the periphery of the lesion. Our results indicate that pre-treatment with AT₁-antagonists such as candesartan could be of benefit in the prevention and treatment of brain ischaemia.

Key Words: renin angiotensin system • angiotensin receptors • genetic hypertension • stroke • brain injury

Journal of Renin-Angiotensin-Aldosterone System, Vol. 2, No. 3, 174-179 (2001)
DOI: 10.3317/jraas.2001.024


CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				G. C. Newman, H. Bang, S. I. Hussain, and J. F. Toole Association of diabetes, homocysteine, and HDL with cognition and disability after stroke Neurology, November 27, 2007; 69(22): 2054 - 2062. [Abstract] [Full Text] [PDF]

				J. Zhou, J. Pavel, M. Macova, Z.-X. Yu, H. Imboden, L. Ge, T. Nishioku, J. Dou, E. Delgiacco, and J. M. Saavedra AT1 Receptor Blockade Regulates the Local Angiotensin II System in Cerebral Microvessels From Spontaneously Hypertensive Rats Stroke, May 1, 2006; 37(5): 1271 - 1276. [Abstract] [Full Text] [PDF]

				J. P. Forder, D. H. Munzenmaier, and A. S. Greene Angiogenic protection from focal ischemia with angiotensin II type 1 receptor blockade in the rat Am J Physiol Heart Circ Physiol, April 1, 2005; 288(4): H1989 - H1996. [Abstract] [Full Text] [PDF]

				H. Ando, J. Zhou, M. Macova, H. Imboden, and J. M. Saavedra Angiotensin II AT1 Receptor Blockade Reverses Pathological Hypertrophy and Inflammation in Brain Microvessels of Spontaneously Hypertensive Rats Stroke, July 1, 2004; 35(7): 1726 - 1731. [Abstract] [Full Text] [PDF]

				I. Kusaka, G. Kusaka, C. Zhou, M. Ishikawa, A. Nanda, D. N. Granger, J. H. Zhang, and J. Tang Role of AT1 receptors and NAD(P)H oxidase in diabetes-aggravated ischemic brain injury Am J Physiol Heart Circ Physiol, June 1, 2004; 286(6): H2442 - H2451. [Abstract] [Full Text] [PDF]