| | Principal Investigators
| Juan M. Saavedra, M.D. |
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Dr. Saavedra is chief of the Section on Pharmacology, Division of Intramural Research Programs,
National Institute of Mental Health, National Institutes of Health. He graduated from Medical School in
1965 and was board certified in Psychiatry in 1970 at the University of Buenos Aires, Argentina.
He joined the laboratory of Julius Axelrod (Section on Pharmacology, Laboratory of Clinical Science,
NIMH) as a Guest Researcher in 1971, was a Fogarty International Fellow from 1972-1973,
Visiting Scientist from 1973 to 1979, and Medical Officer (Psychiatry, Civil Service Excepted Appointment)
from 1979 to 1983. From 1983-1988 he joined the Section on Clinical Pharmacology, Laboratory of
Clinical Science, NIMH, and in 1989 he became chief of the newly created Section on Pharmacology,
DIRP, NIMH. Dr. Saavedra is also a Research Professor of Psychiatry, Department of Psychiatry,
Uniformed Services School of the Health Sciences, Bethesda, Maryland. |
| Research Interests |
| Dr. Saavedra's laboratory studies basic molecular mechanisms controlling the reaction to stress, and basic mechanisms related to the control of the cerebral circulation with special interest on mechanisms of protection against brain ischemia and stroke. The current focus is the role of the brain Angiotensin system, and in particular that of Angiotensin II AT1 receptors, because receptor blockade decreases the hypothalamic-pituitary-adrenal and sympathetic responses to stress, and protects from brain ischemia and stroke. The approach is multidisciplinary, including neuroanatomy, biochemistry, pharmacology, molecular biology and neurosurgery components. |
| Representative Selected Recent Publications: |
- Armando, I., Carranza, A., Nishimura, Y., Hoe, K-L., Barontini, M., Terrón, J.A., Falcón-Neri, A., Ito, T., and Saavedra, J.M.:
Peripheral administration of an Angiotensin II AT1 receptor antagonist decreases the hypothalamic-pituitary-adrenal response to stress.
Endocrinology, 142:3880-3889, 2001.
- Armando, I., Terrón J. A., Falcón-Neri, A., Ito, T., Häuser, W., Inagami, T., and Saavedra, J.M.: Increased
Angiotensin II AT1 receptor expression in paraventricular nucleus and hypothalamic-pituitary-adrenal axis stimulation in AT2 receptor gene disrupted mice. Neuroendocrinology, 76:137-147, 2002.
- Hoe, K-L., and Saavedra, J.M.: Site-directed mutagenesis of the gerbil and human Angiotensin II AT1 receptors identifies amino acid residues attributable to the binding affinity for the non-peptidic antagonist losartan.
Molecular Pharmacology, 61:1404-1415, 2002.
- Ito, T., Yamakawa, H.,
Bregonzio, C., Terrón, J.A., Falcón-Neri,
A., and Saavedra, J.M.: Protection against ischemia
and improvement of cerebral blood flow in genetically
hypertensive rats by chronic pretreatment with an
Angiotensin II AT1 antagonist. Stroke 33:2297-2303,
2002.
- Yamakawa, H., Jezova,
M., and Saavedra, J.M.: Normalization of endothelial
and inducible nitric oxide synthase expression in
brain microvessels of spontaneously hypertensive rats
by Angiotensin II AT1 receptor inhibition. J. Cereb.
Blood Flow Metab. (in press).
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