Angiotensin 1-7 vs Angiotensin II

Comparative Analysis

Angiotensin 1-7 and Angiotensin II represent two opposing forces within the renin-angiotensin system (RAS), functioning as biological counterbalances that regulate cardiovascular homeostasis through fundamentally different mechanisms. While both peptides originate from the same angiotensinogen precursor, their physiological effects create a delicate equilibrium essential for maintaining optimal blood pressure and cardiovascular health. Angiotensin II, the classical effector of the RAS, operates through AT1 receptors to promote vasoconstriction, aldosterone release, and sodium retention. This peptide increases peripheral vascular resistance, enhances cardiac contractility, and stimulates the sympathetic nervous system, collectively elevating blood pressure. Its actions extend beyond cardiovascular regulation to include cellular proliferation, inflammation promotion, and oxidative stress induction. These effects make Angiotensin II a primary target for hypertension management through ACE inhibitors and ARBs. In contrast, Angiotensin 1-7 functions as the protective arm of the RAS, primarily acting through the Mas receptor to produce vasodilation, anti-inflammatory effects, and cardioprotection. This heptapeptide promotes nitric oxide release, enhances endothelial function, and exhibits anti-fibrotic properties. Its actions directly oppose those of Angiotensin II, creating a counter-regulatory mechanism that prevents excessive vasoconstriction and tissue damage. The enzymatic pathways generating these peptides differ significantly. Angiotensin II formation relies heavily on ACE conversion from Angiotensin I, while Angiotensin 1-7 can be produced through multiple routes, including direct ACE2-mediated conversion from Angiotensin II or alternative pathways from Angiotensin I. This diversity in formation pathways suggests evolutionary importance in maintaining cardiovascular balance. Receptor selectivity distinguishes these peptides functionally. Angiotensin II's high affinity for AT1 receptors triggers rapid vasoconstriction and aldosterone release, while its interaction with AT2 receptors may produce opposing effects. Angiotensin 1-7's selective binding to Mas receptors consistently produces protective cardiovascular effects, including improved insulin sensitivity and reduced cardiac remodeling. Clinical implications reveal their therapeutic potential in opposite directions. While Angiotensin II analogs might benefit patients with severe hypotension or distributive shock, Angiotensin 1-7 shows promise for treating hypertension, heart failure, and metabolic disorders. Research indicates that Angiotensin 1-7 may protect against diabetic complications, reduce cardiac fibrosis, and improve endothelial dysfunction. The balance between these peptides appears crucial for cardiovascular health. Conditions favoring Angiotensin II dominance contribute to hypertension, atherosclerosis, and cardiac remodeling, while enhanced Angiotensin 1-7 activity provides cardiovascular protection. Understanding this balance has led to therapeutic strategies aimed at shifting the equilibrium toward the protective Angiotensin 1-7/Mas axis while reducing harmful Angiotensin II/AT1 receptor activation.