Angiotensin II

The renin-angiotensin aldosterone hormonal cascade that regulates blood pressure and water (fluid) balance begins with the biosynthesis of renin by the juxtaglomerular cells that line the afferent (and occasionally efferent) arteriole of the renal glomerulus.^1,2 A drop in blood pressure decreases the perfusion of the juxtaglomerular apparatus, resulting in the release of the enzyme renin. Renin proceeds to cleave angiotensinogen to produce angiotensin I. Angiotensin I is in turn converted to angiotensin II by angiotensin-converting enzyme (ACE), which is found mainly in lung capillaries. Angiotensin II is the major bioactive product of the renin-angiotensin system, binding to receptors on intraglomerular mesangial cells, causing these cells to contract along with the blood vessels surrounding them and causing the release of aldosterone from the adrenal cortex. Angiotensin II has multifaceted effects on aldosterone secretion, vasoconstriction, sodium reabsorption, and fluid volume, all of which serve to raise blood pressure. Laboratory studies with cultured cardiomyocytes have implicated angiotensin as a direct cause of left ventricular hypertrophy associated with hypertension. Angiotensin II also inhibits renin release by the kidney via a feedback mechanism.

Several investigators have found that a subgroup of patients with severe chronic heart failure has elevated plasma angiotensin II levels despite long-term ACE inhibitor use.^3,4 This phenomenon has been referred to as ACE escape or angiotensin II reactivation and has been associated with increased mortality.^4-7