Causes and effects of high blood pressure: a longitudinal approach to genetic cosegregational analysis

Numerous biochemical and physiological phenotypic differences exist between genetically normotensive and hypertensive rats. Only some of these differences, however, are likely to be related to the primary mechanisms causing high blood pressure. Others, and perhaps the majority, will be the result of either the secondary effects of hypertension or the result of incidental genetic differences between the strains that bear no relationship to the difference in blood pressure. Cosegregational analysis by cross-breeding normotensive and hypertensive strains permits the identification of phenotypes that are genetically linked to high blood pressure. However, cosegregational analyses are still prone to the confounding effects of hypertension per se, which can obscure important phenotypic traits and might even mimic Mendelian inheritance of phenotypes by producing qualitative shifts in gene expression. This paper discusses a longitudinal approach to genetic analysis designed to increase the sensitivity with which primary causes of high blood pressure are identified, by beginning the analysis during the development of high blood pressure. At this stage, phenotypic abnormalities causing blood pressure to rise are most likely to be present, and the blood pressure elevation is small so that the confounding effects of elevated arterial pressure are minimized.