From animal models to humans.
1. Essential hypertension is a mixture of several 'hypertensions' with different aetiologies. Analyses of inbred rat models of hypertension have so far provided several candidate loci and genes that may be responsible for hypertension. Among them, SA and alpha-adducin were evaluated in humans both by linkage and association analyses. However, the results are still controversial. Two major reasons may account for these discrepancies. 2. Heterogeneity of human essential hypertension still keeps us from comprehensive conclusions. Comparative analysis of more than one homogeneous population may be necessary to overcome this problem. 3. As in the case of SA, a lack of information on the physiological or pathophysiological roles of candidate genes makes it difficult to evaluate them in human hypertension. Efforts to find good intermediate phenotypes regulated directly by putative hypertension genes are essential to dissect a heterogeneous mixture of 'hypertensions'. In this context, physiological studies on congenic strains as well as conventional rat models will become important.
Department of Laboratory Medicine, Shimane Medical University, Izumo, Japan. nabika@shimane-med.ac.jp
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D000818:Animals; D002148:Calmodulin-Binding Proteins / Q000235:genetics; D003066:Coenzyme A Ligases; D004195:Disease Models, Animal; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D011506:Proteins / Q000235:genetics; D051381:Rats; D011919:Rats, Inbred Strains; D000099291:Adducins
D002148:Calmodulin-Binding Proteins; D003066:Coenzyme A Ligases; D011506:Proteins; D000099291:Adducins; C081817:Acsm3 protein, rat