New aspects of the renin-angiotensin system in blood pressure regulation.
The renin-angiotensin system, composed of enzymatic and signal-transduction cascades, plays a key role in the regulation of arterial blood pressure and in the development of certain forms of experimental and human hypertension. The products of this system, angiotensin peptides, exert a wide range of physiologically important effects on many tissues, including those of the cardiovascular system, through their actions on angiotensin receptors. Molecular genetic and transgenic studies have begun to implicate some of the genes encoding components of the renin-angiotensin system in the development of cardiovascular diseases. Recently, we succeeded in generating mice homozygous for a targeted disruption of the angiotensinogen gene (the only known precursor of angiotensins), resulting in the complete loss of angiotensin signals in vivo. Here, we review new developments related to the functional analysis of the renin-angiotensin system, in particular, by focusing on transgenic approaches including gene targeting.
Fukamizu
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Institute of Applied Biochemistry, University of Tsukuba, Tsukuba, Ibaraki 305, Japan.
Murakami
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