The pathophysiology of essential hypertension has been extensively studied over the last 50 years. Peripheral vascular resistance is usually increased in hypertensive individuals. Normally, the autonomic nervous system, kidneys, adrenal cortex, local hormones, and cytokines regulate vascular resistance. Failure of the normal regulation of vascular resistance leads to hypertension. The failure can theoretically occur in any part of the regulatory system. Initially, overactivity of the sympathetic nervous system plays a major role in the development and maintenance of hypertension. The excessive activation of the renin-angiotensin system (RAS) or enhanced sensitivity to its primary effector, Ang II, contributes to the development and maintenance of hypertension. The fact that inhibitors of the formation of Ang II or its antagonists at the receptor level are highly useful antihypertensive drugs supports the likely involvement of RAS in the pathogenesis of hypertension. Since calcium ions are required for the contraction of vascular smooth muscle (VSM), excessive permeability of VSM cells to Ca2 + or altered sodium-calcium exchange may also be involved. Activation of Ang II receptors leads to enhanced entry of calcium ions into VSM cells, so that the calcium and Ang II hypotheses are not mutually exclusive.
Various biochemical abnormalities in VSM cells have been proposed to play a role in the development of essential hypertension, including: (1) increased ratio of cyclic guanosine monophosphate/cyclic adenosine monophosphate (AMP); (2) decreased basal adenylyl cyclase; and (3) altered activity of cyclic AMP-dependent protein kinase. It is not clear whether any of these changes are consistently present in hypertensive individuals and whether they are causative or secondary to another abnormality in the biochemistry of VSM.
Over the last decade genetics of essential hypertension has been investigated.8 The estimates for the extent of genetic contributions to the pathogenesis of essential hypertension range from 30% to 50%. The studies have failed, however, to identify one single gene responsible for essential hypertension. It appears that multiple candidate and susceptibility genes may contribute to the disease. Candidate genes have been identified in the RAS. Genetic linkages between ACE and essential hypertension have been suggested.9 Polymorphisms of the Ang II receptor (AT^ gene have been related to differential responses to antihypertensive drugs and severe forms of essential hypertension were found to be associated with a specific defect in this gene.10 Mutations of subunits of the epithelial sodium-channel gene have been found in Liddle's syndrome that is known to be associated with increased renal reabsorption of sodium and hypertension.11 Linkages between adrenergic receptor genes and hypertension have been reported. b2-Adrenergic receptor gene, known to affect blood flow and arterial pressure, has been implicated in the genetics of essential hypertension. It has been suggested that essential hypertension is caused by a combination of small quantitative changes in the expression of many susceptibility genes with the environmental factors.7'12
The mutations of susceptibility genes may also be responsible for the excessive sensitivity to salt and higher risk for hypertension in black Americans. Hypertension appears to be primarily responsible for the higher mortality of black Americans from heart disease, renal failure, and stroke (see 6.10 Stroke/Traumatic Brain and Spinal Cord Injuries; 6.25 Renal Dysfunction in Hypertension and Obesity; 6.33 Antiarrythmics).13
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Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...