Angiotensin II

Angiotensin II is an endogenous octapeptide and the primary effector of the renin-angiotensin-aldosterone system (RAAS). It is a potent vasoconstrictor that regulates blood pressure, fluid balance, and cardiovascular homeostasis. The synthetic form (Giapreza) received FDA approval in 2017 for treatment of distributive shock in critically ill patients who fail catecholamine therapy.

Angiotensin II binds primarily to AT1 receptors on vascular smooth muscle and the adrenal cortex. AT1 activation triggers Gq-mediated signaling leading to vasoconstriction, aldosterone secretion, sodium and water retention, and sympathetic nervous system potentiation. These combined effects rapidly increase mean arterial pressure. AT2 receptors mediate opposing vasodilatory and anti-proliferative effects. In septic shock, exogenous Ang II restores vasomotor tone and reduces catecholamine requirements.

The FDA approval of Giapreza was supported by the ATHOS-3 trial (2017), a randomized controlled trial demonstrating that Angiotensin II significantly increased MAP in patients with distributive shock compared to placebo. Research continues on Ang II's roles in cardiac remodeling, renal function, and as a therapeutic target in hypertension, heart failure, and COVID-19 (ACE2 receptor modulation). Extensive evidence base from decades of RAAS pharmacology.