A multifactorial and heterogeneous etiology of essential hypertension has been proposed.[12] However, some initiating factors may be dampened as the hypertensive state progresses.[13] The following factors have been shown to disrupt the delicate balance of cardiac output and resistance, ultimately resulting in hypertension:

  • Disturbance of autoregulation (reflex and persistently increasing vascular resistance to match an increased cardiac output)[14]

  • Excess sodium intake through a variety of mechanisms[15][16]

  • Renal sodium retention[17][18][19][20]

  • Dysregulation of the renin-angiotensin-aldosterone axis, with elevated plasma renin activity[21]

  • Increased sympathetic drive[22]

  • Increased peripheral resistance[23]

  • Endothelial dysfunction[24]

  • Cell membrane transporter perturbations[25]

  • Insulin resistance/hyperinsulinemia.[26]


Blood pressure (BP), the product of cardiac output and peripheral vascular resistance, is affected by preload, contractility, vessel hypertrophy, and peripheral constriction. The pathology associated with, and the perpetuation of, the hypertensive state involves structural changes, remodeling, and hypertrophy in resistance arterioles.[13] These changes have also been associated with the early and progressive development of small vessel atherosclerosis, which is likely the cause of end-organ damage seen in advanced hypertension. This occurs through a complex series of interrelated processes including thrombosis, endothelial injury and dysfunction, the inflammatory cascade, oxidative stress, and autonomic dysregulation in the setting of genetic predisposition.[27]

Trials have demonstrated the importance of systolic BP in the pathophysiology of hypertension and its associated complications, which differs from older conventional thinking.[28] The rise in systolic BP continues throughout life, in contrast to diastolic BP, which increases until approximately 50 years of age, tends to level off over the following decade, and may stabilize or decline subsequently.

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