Pathophysiology of Hypertension

Cardiac output and peripheral resistance

Maintenance of a normal blood pressure is dependent on the balance between the cardiac output and peripheral vascular resistance. Most patients with essential hypertension have a normal cardiac output but a raised peripheral resistance. Peripheral resistance is determined not by large arteries or the capillaries but by small arterioles, the walls of which contain smooth muscle cells. Contraction of smooth muscle cells is thought to be related to a rise in intracellular calcium concentration, which may explain the vasodilatory effect of drugs that block the calcium channels. Prolonged smooth muscle constriction is thought to induce structural changes with thickening of the arteriolar vessel walls possibly mediated by angiotensin, leading to an irreversible rise in peripheral resistance.
It has been postulated that in very early hypertension the peripheral resistance is not raised and the elevation of the blood pressure is caused by a raised cardiac output, which is related to sympathetic overactivity. The subsequent rise in peripheral arteriolar resistance might therefore develop in a compensatory manner to prevent the raised pressure being transmitted to the capillary bed where it would substantially affect cell homeostasis.


Renin-angiotensin system

The renin-angiotensin system may be the most important of the endocrine systems that affect the control of blood pressure. Renin is secreted from the juxtaglomerular apparatus of the kidney in response to glomerular underperfusion or a reduced salt intake. It is also released in response to stimulation from the sympathetic nervous system.
Renin is responsible for converting renin substrate (angiotensinogen) to angiotensin I, a physiologically inactive substance which is rapidly converted to angiotensin II in the lungs by angiotensin converting enzyme (ACE). Angiotensin II is a potent vasoconstrictor and thus causes a rise in blood pressure. In addition it stimulates the release of aldosterone from the zona glomerulosa of the adrenal gland, which results in a further rise in blood pressure related to sodium and water retention.