Essential Hypertension

Role of sympathetic nervous system in hypertension: Development and maintenance of hypertension is associated with the increased activity of the sympathetic nervous system due to the continuous stimulation of the heart, peripheral vasculature and kidneys which causes increased cardiac output, increased vascular resistance and fluid retention.

This aforementioned effect is observed more frequently in patients with prehypertension (systolic pressure 120-139 mmHg and diastolic pressure 80-89 mmHg) or hypertension rather than normotensive patients. A commonly accepted indicator of hypertension is high resting pulse rate which may be the consequence of increased sympathetic nervous activity. Moreover, some patients with hypertension exhibit higher levels of circulating plasma catecholamines at rest than normotensive persons.

Abnormal Na⁺ transport: In many cases of hypertension  the Na-K pump (Na⁺, K⁺-ATPase) is defective or inhibited; or alternatively, permeability to Na⁺ may be increased, resulting in irregular Na⁺ transport across the cell wall irregular. The outcome of such disruption is increased intracellular Na+, which renders a cell more sensitive to sympathetic stimulation. Ca²⁺ flux typically follows that of Na⁺, thus, accumulation of intracellular Ca²⁺ may be responsible for the increased sensitivity. Na⁺, K⁺-ATPase can pump norepinephrine back into sympathetic neurons, thus inactivating this neurotransmitter, thus inhibition of this mechanism may also enhance the effect of norepinephrine, increasing blood pressure.

Congenital (inherited) blood pressure disorders: It has been observed that mutations in at least 10 genes raise or lower blood pressure through a common pathway, by increasing or decreasing water and salt reabsorption by the kidneys. Three rare forms of mendelenian hypertensive syndromes caused by genetic mutations have been identified. These syndromes are glucocorticoid remediable aldosteronism, Liddle’s syndrome and apparent mineralocorticoid excess.

Endothelial dysfunction and vasoactive substances: Investigations of human essential hypertension have correlated this disorder with endothelial dysfunction. Vascular endothelial cells play an important role in cardiovascular regulation by production of potent local vasoactive substances, including: 1) nitric oxide, a vasodilator molecule which is produced by arterial and venous endothelium and diffuses through the vessel wall into the smooth muscle, 2) the vasoconstrictor peptide endothelin, which produces a salt sensitive rise in blood pressure. 3) Atrial natriuretic peptide, which is produced in response to increased blood volume from the atria of the heart, in order to increase the excretion of sodium and water from the kidneys, so a defect in this system may cause fluid retention and hypertension. 4) Bradykinin, a potent vasodilator.

Arterial senescence - arteriosclerosis and atherosclerosis: As an individual is ageing, significant deleterious changes occur in the structure of arterial walls, most importantly in the large elastic arteries, the coronary arteries and the large arteries that supply the brain with blood.  Age-related pathologies in which these vessels are involved, include principally arteriosclerosis and atherosclerosis. Arteriosclerosis involves loss of elasticity and hardening of the arteries. These alterations greatly increase resistance to blood flow, reducing the normal circulation of blood and greatly increasing cardiac work load. Atherosclerosis is a common variant of arteriosclerosis, involving deposition of fatty plaques on the internal surface of affected vessels. As these plaques enlarge, they narrow the vessel lumens and reduce their elasticity. Often, the plaques enlarge to the point of obstructing blood flow, thereby putting tissue below the blockage at-risk for ischemic injury.