Pathogenesis

Pathogenesis
Changes in blood pressure tend to occur over time. Development of hypertension is a slow insidious process. We have been taught to wait and to plan for treatment once the blood pressure reaches a level we deem appropriate for treatment.

Traditionally, this level has been 140/90 mm Hg. Studies are currently underway to determine whether it makes sense to intervene sooner and thus preventing development of true hypertension with behavioral techniques and pharmacotherapy.

For example, it would be helpful to know whether treatment started at 130 mm Hg would prevent progression to systolic levels in the 140s: this information could have an important impact on determining risk of cardiovascular events and on decisions regarding expensive pharmacotherapy.

This intriguing issue delves into the pathogeneses of hypertensive cardiovascular disease. Why is a high blood pressure injurious to the circulation?

Although not known with certainty, most experts would suggest that rising arterial pressures creates increase mechanical stretch and strain on vascular beds, which results in localized areas of injuries.


With repetitive injury and subsequent repair over time, remodeling and restructuring occurs, which affects compliance if the elastic vessels and leads to a loss of distensibility. Subsequent calcification ensues.

The net result is increasing peripheral vascular resistance and higher levels of arterial pressure.

There is also increasing evidence that subtle derangements in sodium and water handling by the kidney may lead to development of higher levels of blood pressure through increasing blood volume.

It is also theorized that hypertension could injure the kidney and interfere with sodium and water excretion.

Thus it is a combination of factors that result in increasing levels of blood pressure and subsequent vascular and target organ injury.

Many factors are involved in the injury process. For example, dietary salt is a substantial concern especially in people who have measurable increases in blood pressure in response to increased ingestion of salt.

There are also data suggesting that dietary salt may cause non-hemodynamic injury to the circulation and heart.

Neurohormones such as angiotensin II and norepinephrine have been implicated in leading to vascular disease.

Angiotensin II, in particular, has been identified as a major factor in the injury and repair responses that occur in blood vessels, the heart, and the kidneys.

Drugs that block the rennin-angiotensin system have a potent capability of attenuating structural changes that occur in vascular beds.

The sympathetic nervous system employs catecholamines, such as norepinephrine, to raise blood pressure.

Catecholamines have also been linked to the pathogenesis of hypertension. They increase heart rate and cardiac output and raise blood pressure. The impact of stress and hyperexcitability on raising blood pressure mediated through effects of both the renin-angiotensin system and the sympathetic nervous system.

Therefore, there is great interest in targeting neurohormonal systems with various pharmacotherapies to prevent progression of hypertensive cardiovascular disease.

Other hormones such as insulin and cytokines may contribute to development of vascular disease, as well.
Pathogenesis