Genetics of experimental hypertension.
Experimental models of genetic hypertension are used to develop paradigms to study human essential hypertension while removing some of the complexity inherent in the study of human subjects. Since 1991 several quantitative trait loci responsible for blood pressure regulation have been identified in various rat crosses. More recently, a series of interesting quantitative trait loci influencing cardiac hypertrophy, stroke, metabolic syndrome and renal damage has also been described. It is recognized that the identification of large chromosomal regions containing a quantitative trait locus is only a first step towards gene identification. The next step is the production of congenic strains and substrains to confirm the existence of the quantitative trait locus and to narrow down the chromosomal region of interest. Several congenic strains have already been produced, with further refinement of the methodology currently in progress. The ultimate goal is to achieve positional cloning of the causal gene, a task which has so far been elusive. There are several areas of cross-fertilization between experimental and human genetics of hypertension, with a successful transfer of two loci directly from rats to humans and with new pharmacogenetic approaches which may be utilized in both experimental and clinical settings.
Dominiczak
A F
AF
Department of Medicine and Therapeutics, University of Glasgow, Western Infirmary, UK. anna.dominiczak@clinmed.gla.ac.uk
Clark
J S
JS
Jeffs
B
B
Anderson
N H
NH
Negrin
C D
CD
Lee
W K
WK
Brosnan
M J
MJ
D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001794:Blood Pressure / Q000235:genetics; D002874:Chromosome Mapping; D004195:Disease Models, Animal; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000235:genetics*; D051379:Mice; D010641:Phenotype; D019655:Quantitative Trait, Heritable; D051381:Rats; D013045:Species Specificity
D000959:Antihypertensive Agents