Between 1950 and 1960, remarkable advances were made in the develQpment Qf antihypertensive drugs, but since then, prQgress has been less rapid. This dQes nQt mean that no. new drugs have been intrQduced: Qn the cQntrary, their number has increased sharply; but since the advent Qf the beta-adrenergic blQckers no. new pharmacQdynamic principle has been discQvered that CQuid be applied widely as an antihypertensive. This has nQt been fQr want Qf effQrts, because many attempts have been made to. find new ways and means Qf influencing blQQd- pressure regulatiQn Qr the mechanisms invQlved in the pathQgenesis Qf hypertensiQn. HQwever, the results Qf these endeavQrs have mQstly been disapPQinting. Even thQugh high blQQd pressure can be treated mQre satisfactQrily tQday than many Qther diseases, the success achieved in cQmbating Qne Qf man's mQst frequent ailments shQuld nQt induce cQmplacency, but rather stimulate research tQwards further imprQvements. The present standstill affQrds an QPPQrtunity to. review the field Qf antihy- pertensive agents, fQr it is unlikely that fundamentally new drugs will appear in the near future. AlthQugh greater knQwledge has been gained Qf the mechanisms Qf blQQd-pressure regulatiQn and Qf the pathQgenesis Qf hypertensiQn, these ad- vances have had no. direct cQnsequences in the search fQr new therapeutics.

Cardiovascular disease and mortality risk are significantly increased in people with metabolic syndrome, a cluster of interrelated metabolic disorders including obesity, insulin resistance, glucose intolerance, dyslipidemia and hypertension. A complex interplay between predisposing and protective factors ultimately determines whether an individual will develop this set of disorders or not. Genetic factors are one of the significant contributors that predispose to, or protect against, each component of the metabolic syndrome. As in other complex diseases and traits, such genetic factors are likely to be multiple and interacting, with individual polymorphisms producing only a moderate effect. The identification of genetic variants influencing the metabolic syndrome is of great importance to understanding pathogenesis, identifying groups of individuals with different relative risk, and developing or improving therapies against this cluster of metabolic disorders. This has greatly stimulated both theoretical and applied genetic research in recent years. A range of new analytical tools has been developed for the dissection of complex traits. Applied genetic analyses have identified large numbers of candidate markers and chromosomal regions (over 600 for obesity, which represents only one of the disorders of this cluster). In this chapter, the authors present a basic overview of the genetic approaches currently used for the identification of candidate genetic factors involved in the metabolic syndrome. The authors also summarise current evidence suggesting that genetic variants within elements of the endocrine system are directly involved in the risk of the metabolic syndrome. The authors focused their attention on endocrine pathways for which candidate genetic variants have been identified, and they introduced the foundations of a new hypothesis which postulates the involvement of a network of endocrine genetic setpoints as a combined contributor to the risk of the metabolic syndrome.