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• Discovery

  Angiotensin II is the active peptide hormone of the reninangiotensin system (RAS) with broad functions, including a vasopressor effect and thirst stimulation. It is a drug target for hypertension and renal diseases. In 1940, two groups of researchers separately discovered a potent vasoconstrictor by incubating plasma with renin; the substance was named both “angiotonin” and “hypertensin.” In 1958, they agreed to rename it “angiotensin” (angio=blood vessel; tensin=tension).;

• Structure

  Ang II is a linear peptide with no known secondary modification. Ang II is produced by the subsequent cleavage of angiotensinogen (AGT) by renin and angiotensin I (Ang I) by ACE (See Renin Angiotensin System). Mr. 1046 of Ang II in humans. Freely soluble in water.;

• Gene, mRNA, and mRNA

  AGT is located on chromosome 1q42.2 in humans. AGT belongs to the SERPIN family A, member 8. AGT protein sequences are highly variable but the functional domains (Ang I) are relatively conserved among vertebrates. Ang I sequences were identified by the incubation of a renin source (kidney extract) and an angiotensinogen source (plasma). Lamprey Ang I with sequence NRVYVHPFTL was first sequenced using peptide purification. However, the lamprey genome data suggested a different Ang I sequence, and was later confirmed as the native AGT. The purified teleost-type Ang I produced in the buccal gland was suggested to be involved in endocrine mimicry to reduce host immunorejection.;

• Agonist

  A nonpeptide ligand, L-162,313 was shown to bind to AT1A, AT1B, and the AT2 receptor and act as an agonist on AT1A and AT1B receptors in mice (34.9 and 23.3% of the maximum response of Ang II, respectively). Early studies used CGP42112A as the agonist for the AT2 receptor but compound 21, with little affinity for the AT1 receptor, was recently developed as a specific agonist of the AT2 receptor in humans.;

• Antagonist

  Saralasin ([Sar1 ], [Ala8 ]-Ang II) is a partial agonist of angiotensin II receptors, though it is commonly mistaken as a competitive antagonist. Antagonists including losartan, irbesartan, olmesartan, candesartan, and valsartan are commonly used clinically as AT1 blockers. Two AT2 receptor antagonists, PD123177 (discontinued) and PD123319 (available), were developed to inhibit AT2 activities.;

• Biological functions

  Ang II/AT1 axis mediates vasoconstriction, thirst, release of vasopressin and aldosterone, renal sodium reabsorption, fibrosis, inflammation, angiogenesis, vascular aging, and atherosclerosis. Ang II-induced effects included blood pressure control; drinking; adrenergic stimulation; modulation of the ion pump and transporter activities in the gill, kidney, and intestine in fish; control of the filtering nephron population in fish; and regulation of ventral skin absorption in amphibians. The injection of Ang II significantly increased ventral skin drinking in the frog. Lamprey Ang II is a vasodepressor instead of a vasopressor when injected intraarterially. The intracerebroventricular (ICV) injection of Ang II into the trout increased the systemic blood pressure, heart rate, and ventilation rate. The ICV injection of Ang II elicits tachycardia in contrast to bradycardia when injected peripherally. Central Ang II injection also inhibits the vagal-mediated baro-reflex, indicating that brain RAS is involved in the heart rate control.
  The AT2 receptor is mostly embryonic. The expression decreases in adults and is confined in certain tissues such as the kidney. The effects of AT2 are often antagonistic to AT1, and activation of the AT2 receptor usually indicates a pathophysiological condition of AT1-mediated action with potential harmful consequences. AT2 is abundantly expressed in the spleen of the adult eel, which suggests an immune-related function.;

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