II. Physiology: Overall Process

  1. Step 1: Renin release
    1. Stimulators of renin release
      1. Kidney detects decreased effective blood flow
      2. Increased sympathetic tone
      3. Renal Artery Stenosis
    2. Renin secreted from renal cortex
      1. Secreted from juxtaglomerular cells
      2. Cells located at afferent arteriole of glomerulus
  2. Step 2: Renin mediated step
    1. Renin cleaves Angiotensinogen to Angiotensin I
  3. Step 3: Angiotensin-converting enzyme (ACE) mediated
    1. Angiotensin I converted by ACE to Angiotensin II
    2. Conversion by ACE occurs in pulmonary vasculature
  4. Step 4: Angiotensin II Effects
    1. Sodium and water retention
      1. Stimulates aldosterone secretion
      2. Directly affects renal tubule
    2. Vasomotor tone balance
      1. Angiotensin II is a potent Vasoconstrictor
        1. Increases systemic vascular resistence
        2. May be Norepinephrine mediated
      2. Antagonist to nitric oxide (potent vasodilator)

III. Physiology: Angiotensin II Effects

  1. Increases oxygen demand
  2. Increases coronary and renal Vasoconstriction
  3. Increases Preload and Afterload
  4. Predisposes to Left Ventricular Hypertrophy
  5. Increases Catecholamine release (e.g. Norepinephrine)
  6. Increases aldosterone

IV. Agents that decrease Angiotensin II levels

V. References

  1. Rose (1987) Pathophysiology of Renal Disease, p. 474-7
  2. Bicket (2002) Am Fam Physician 66(3):461-8 [PubMed]

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Ontology: Angiotensinogen (C0003017)

Definition (CSP) a serum alpha-globulin synthesized in the liver, which is cleaved by renin to form angiotensin I.
Definition (MSH) An alpha-globulin of about 453 amino acids, depending on the species. It is produced by the liver and secreted into blood circulation. Angiotensinogen is the inactive precursor of natural angiotensins. Upon successive enzyme cleavages, angiotensinogen yields angiotensin I, II, and III with amino acids numbered at 10, 8, and 7, respectively.
Concepts Biologically Active Substance (T123) , Amino Acid, Peptide, or Protein (T116)
MSH D000808
SnomedCT 54592005
LNC LP15390-5, MTHU008275
English Hypertensinogen, Proangiotensin, Renin Substrate, Renin-Substrate, Angiotensinogen (protein renin substrate), Angiotensinogen, Serpin A8, Angiotensinogen [Chemical/Ingredient], angiotensinogen, renin substrate, Angiotensinogen (substance)
Swedish Angiotensinogen
Czech angiotensinogen
Finnish Angiotensinogeeni
French Proangiotensine, Substrat de la rénine, Angiotensinogène, Hypertensiogène
Russian GIPERTENZINOGEN, RENIN-SUBSTRAT, ANGIOTENZINOGEN, АНГИОТЕНЗИНОГЕН, ГИПЕРТЕНЗИНОГЕН, РЕНИН-СУБСТРАТ
Italian Substrato reninico, Ipertensinogeno, Angiotensinogeno
Polish Hipertensynogen, Angiotensynogen
Japanese アンギオテンシノーゲン, アンジオテンシノゲン, アンジオテンシノーゲン, ハイパーテンシノーゲン, レニン基質
Spanish angiotensinógeno (sustancia), angiotensinógeno, Renina-Sustrato, Angiotensinógeno, Hipertensinógeno
German Angiotensinogen, Hypertensinogen, Reninsubstrat
Portuguese Angiotensinogênio, Hipertensinogênio, Substrato da Renina

Ontology: Angiotensins (C0003018)

Definition (NCI) Expressed in liver by human AGT Gene (Serpin Family), secreted 485-aa 53-kDa Angiotensinogen is cleaved by renin (in response to lowered blood pressure) to inactive decapeptide Angiotensin I, which is cleaved by ACE to generate active octapeptide vasopressor Angiotensin II (maintains blood pressure and regulates the volume and mineral balance of body fluids). Angiotensin II is cleaved to Angiotensin III heptapeptide, an aldosterone stimulant.
Definition (CSP) angiotensin I, an inactive decapeptide, is cleaved by angiotensin converting enzyme to form the octapeptide angiotensin II, a powerful vasopressor, which is then cleaved to the heptapeptide angiotensin III, an aldosterone stimulant.
Definition (MSH) Oligopeptides which are important in the regulation of blood pressure (VASOCONSTRICTION) and fluid homeostasis via the RENIN-ANGIOTENSIN SYSTEM. These include angiotensins derived naturally from precursor ANGIOTENSINOGEN, and those synthesized.
Concepts Pharmacologic Substance (T121) , Biologically Active Substance (T123) , Amino Acid, Peptide, or Protein (T116)
MSH D000809
SnomedCT 304274007, 9974009
LNC LP40491-0
English Angiotensin, Angiotensins, Angiotensins [Chemical/Ingredient], angiotensin, angiotensins, Angiotensin (substance), Angiotensin, NOS
Swedish Angiotensiner
Czech angiotensiny
Finnish Angiotensiinit
Russian ANGIOTENZINY, ANGIOTENZIN, АНГИОТЕНЗИН, АНГИОТЕНЗИНЫ
Italian Angiotensina, Angiotensine
Croatian ANGIOTENZINI
Polish Angiotensyny
Japanese アンギオテンシン, アンギオテンシン類, アンギオトニン, アンジオテンシン, アンジオテンシン類, アンジオトニン, ハイパーテンシン
Norwegian Angiotensiner, Angiotensin
Spanish angiotensina (sustancia), angiotensina, Angiotensina, Angiotensinas
French Angiotensines, Angiotensine
German Angiotensine, Angiotensin
Portuguese Angiotensina, Angiotensinas

Ontology: Renin (C0035094)

Definition (CHV) an enzyme released by the kidneys that helps regulate blood pressure
Definition (CHV) an enzyme released by the kidneys that helps regulate blood pressure
Definition (NCI) Renin (406 aa, ~45 kDa) is encoded by the human REN gene. This protein plays a role in activation of angiotensin.
Definition (CSP) do not confuse with "rennin" which is another name for CHYMOSIN, EC 3.4.23.4.
Definition (MSH) A highly specific (Leu-Leu) endopeptidase that generates ANGIOTENSIN I from its precursor ANGIOTENSINOGEN, leading to a cascade of reactions which elevate BLOOD PRESSURE and increase sodium retention by the kidney in the RENIN-ANGIOTENSIN SYSTEM. The enzyme was formerly listed as EC 3.4.99.19.
Concepts Amino Acid, Peptide, or Protein (T116) , Enzyme (T126)
MSH D012083
SnomedCT 112052004
LNC LP15273-3, LP32149-4, MTHU003186
English Angiotensin Forming Enzyme, Angiotensin-Forming Enzyme, Angiotensinogenase, Renin, angiotensin forming enzyme, angiotensinogenase, Renin [Chemical/Ingredient], renin, renins, EC 3.4.23.15, Renin Precursor, Renal, Angiotensin-forming enzyme, Renin (substance)
Swedish Renin
Czech renin
Finnish Reniini
Russian RENIN, ANGIOTENZINOGENAZA, ANGIOTENZIN-OBRAZUIUSHCHII FERMENT, АНГИОТЕНЗИН-ОБРАЗУЮЩИЙ ФЕРМЕНТ, АНГИОТЕНЗИНОГЕНАЗА, РЕНИН
Japanese アンジオテンシン形成酵素, アンジオテンシノゲナーゼ, アンギオテンシン形成酵素, レニン, アンギオテンシノゲナーゼ
French Angiotensinogénase, Rénine
Croatian RENIN
Polish Renina
Spanish angiotensinogenasa, enzima formadora de angiotensina, renina (sustancia), renina, Renina, Angiotensinogenasa, Enzima Formadora de Angiotensina
German Angiotensin-I-bildendes Enzym, Angiotensinogenase, Renin
Italian Renina
Portuguese Renina, Angiotensinogenase, Enzima Formadora de Angiotensina