Targeting genes in the renin-angiotensin system.
OBJECTIVE
The renin-angiotensin system plays a key role in the regulation of blood pressure and fluid homeostasis. Owing to its critical contribution to blood pressure control, abnormalities of any component in this system can lead to hypertension and cardiovascular diseases. In this review, we will highlight studies using this approach to uncover new perspectives on the physiology of the renin-angiotensin system.


RESULTS
Over the past decade, application of techniques for manipulating the genome of living animals, including gene targeting through homologous recombination in embryonic stem cells, has provided unique insights into the complex biology of the renin-angiotensin system. Along with advances in understanding functions of the classical components of the system, gene targeting has clarified the functions of newly discovered angiotensin-converting enzyme homologues.


CONCLUSIONS
Since pharmacological antagonists of the renin-angiotensin system are widely used in clinical medicine, advances in the gene-targeting experiments of the system have helped to clarify the mechanisms of action of these agents and may provide clues for improved approaches for the treatment of hypertension and kidney diseases.
Le
Thu H
TH
Division of Nephrology and Department of Medicine, Duke University and Durham VA Medical Centers, Durham, North Carolina 27710, USA.
Coffman
Thomas M
TM
D000808:Angiotensinogen / Q000235:genetics; D000818:Animals; D018390:Gene Targeting / Q000379:methods*; D006801:Humans; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D011945:Receptors, Angiotensin / Q000235:genetics; D012083:Renin / Q000235:genetics; D012084:Renin-Angiotensin System / Q000235:genetics*
D011945:Receptors, Angiotensin; D000808:Angiotensinogen; D007703:Peptidyl-Dipeptidase A; D012083:Renin