Blood pressure homeostatis in humans is a result of the coordinated interactions of multiple physiological systems that are affected by many genetic and environmental factors. In many individuals, these factors combine to cause an elevation in blood pressure, or hypertension. Our interest in determinating the mechanisms regulating blood pressure stems from the fact that hypertension is a major health problem of populations worldwide, and causes devastating consequence such as stroke, heart failure and renal failure.

At present, high blood pressure is detected by screening, meaning that it cannot be diagnosed until it has developed. Recommendations for primary prevention of essential hypertension currently emphasize avoidance of factors that predispose to hypertension, such as obesity, physical inactivity, alcoholism and a high salt intake. Although such recommendations, if broadly accepted by the general public, would lead to a healthier population, they are difficult to uphold without patient compliance.

Identification of genetic marlers for a predisposition to hypertension in the future may permit focused intervention on such hypertensinogenic factors. For example, if an individual is found to have a genetic predisposition to impaired sodium homeostatis, the early introduction of salt restriction may help prevent hypertension, or at least delay onset. We may also predict blood pressure responsiveness to specific lifestyle interventions.

Drug Responsiveness

Drug effects are likely to be polygenocally determined. It may be feasible to develop gene markers for individual drug responsiveness in the future. This new field, termed “pharmacogenomics”, well probably help clinicians to prescribe more individualized of empirical treatment, to hypertensive patients. There have been several attempts to raltae genetic polymorphisms to drug responsiveness. There have also been attempts to ralate polymorphisms of the reninangiotensin sytem genes to effects to ACE inhibitors on the heart, and certain gene variants to diuretic responsiveness.

Target Organ Protection

Although many advances have been made in the treatment of hypertension, target organ damage remains a major cause of morbidity, and susceptibility genes may markerdly increase the risk of particular hypertensive complications.

In contrast to the numerous determinants of blood pressure level, it seems likely that target organ failure represents the “weak link” in a process of damage and repair, therefore, a smaller number of genes could predispose an individual to hypertensive complications. Genetic determinants for hypertensive organ damage may be closer to our traditional model of inborn errors of metabolism than to the complex trait of hypertension. Identifications of markers may enable us to intervene early before irreversible changes occur.

Essential hypertension has a complex pathogenesis in which many genetic and environmental factors interact. Identification of the causative genes of monogenic hypertension and its physiological dysfunction is still at an early stage. In the future, high-throughput techniques will accelerate the pace of discovery. Clinical practice in the management of hypertension will be altered by a new understanding of the condition.