The phenotypic patterns of essential @entity101 are the key to identifying " XXXX " genes.

@entity8 @entity101 @entity28 @entity1640 @entity3190 @entity842 @entity74 @entity2412
The genes that cause or increase susceptibility to essential @entity101 (EH) and related animal models remain unknown. Their identification is unlikely to be realized with current @entity74 , because of ambiguities in the genotype-phenotype relationships in these @entity74 . In turn, the phenotype is not just an aggregate of traits, but needs to be related to specific components of the circulatory control system at different stages of EH. Hence, clues about important genes must come through the phenotype, reversing the order of current approaches. A recent systems analysis has highlighted major differences in circulatory control in the two main syndromes of EH: (1) stress-and-salt-related EH (SSR-EH)--a constrictor @entity101 with low blood volume; (2) hypertensive @entity28 --SSR-EH plus @entity28 . Each is initiated through sensitization of central synapses linking the cerebral cortex to the @entity1640 defense area. Several mechanisms are probably involved, including cerebellar effects on baroreflexes. The result is a sustained increase in sympathetic neural activity at stimulus levels that have no effect in normal subjects. Subsequent progression of EH is largely through interactions with non-neural mechanisms, including changes in concentration of vascular autacoids (e.g., @entity842 ) and the amplifying effect of structural changes in large resistance vessels. The rising vasoconstriction increases heterogeneity of blood flow, causing rarefaction (decreased microvascular density) and deterioration of vital organs. SSR-EH also increases food intake in response to stress, but only 40% of these individuals develop hypertensive @entity28 . Their brain ignores the adiposity signals that normally reduce eating. @entity3190 masks the sympathetic vasoconstriction through its dilator action, raises blood volume, whilst renal @entity8 and other @entity2412 are common. In each syndrome the neural and non-neural determinants of @entity101 provide targets for identifying high BP genes. Reading the genome from the phenotype will require new approaches, such as those used in developmental genetics. In addition, transgenic technology may help verify hypotheses and examine whether an observed effect is through single or multiple mechanisms. To obtain answers will require substantial collaborative efforts between physiologists and geneticists.
