From animal models to humans

1. Essential hypertension is a mixture of several 'hypertensions' with diff erent aetiologies, Analyses of inbred rat models of hypertension have so fa r provided several candidate loci and genes that may be responsible for hyp ertension, Among them, SA and alpha-adducin were evaluated in humans both b y linkage and association analyses, However, the results are still controve rsial. Two major reasons may account for these discrepancies. 2. Heterogeneity of human essential hypertension still keeps us from compre hensive conclusions. Comparative analysis of more than one homogeneous popu lation may be necessary to overcome this problem, 3. As in the case of SA, a lack of information on the physiological or path ophysiological roles of candidate genes makes it difficult to evaluate them in human hypertension. Efforts to find good intermediate phenotypes regula ted directly by putative hypertension genes are essential to dissect a hete rogeneous mixture of 'hypertensions', In this context, physiological studie s on congenic strains as well as conventional rat models will become import ant.