Intracerebroventricularly infused [d-Arg1]angiotensin III, is superior to [d-Asp1]angiotensin II, as a pressor agent in rats

Wright, John W.; Roberts, Kim A.; Cook, Vickie I.; Murray, Cathy E.; Sardinia, Michael F.; Harding, Joseph W.

doi:10.1016/0006-8993(90)90428-e

Cited by 33 publications

(24 citation statements)

References 27 publications

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“…In the brain, Ang III, and not Ang II, is the agonist responsible for mediating vasoconstriction and BP elevation via the AT 1 R. 15,[23][24][25][26][27] Ang III was also shown to mediate vasopressin release when administered directly into the 3rd ventricle of the brain. 15,27 Similarly, in the adrenal RAS, aldosterone production is stimulated by Ang III as well as Ang II.…”

Section: Discussionmentioning

confidence: 99%

Conversion of Renal Angiotensin II to Angiotensin III Is Critical for AT ₂ Receptor–Mediated Natriuresis In Rats

et al. 2008

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Abstract-In the kidney, angiotensin II (Ang II) is metabolized to angiotensin III (Ang III) by aminopeptidase A (APA).In turn, Ang III is metabolized to angiotensin IV by aminopeptidase N (APN T he intrarenal renin-angiotensin system (RAS) is separate from the peripheral RAS and contributes independently to the regulation of blood pressure and sodium excretion. [1][2][3][4] All of the precursors of angiotensin peptide synthesis are located within the renal proximal tubule (RPT), including angiotensinogen, renin, and angiotensin converting-enzyme mRNA. [5][6][7][8] Interstitial fluid concentrations of angiotensin II (Ang II) and angiotensin III (Ang III) are far greater (nanomolar) than can be explained solely on the basis of equilibration with circulating concentrations (femtomolar). 9,10 These findings suggest that important influences are exerted by locally generated angiotensins. Additionally, the 2 major receptor subtypes that mediate actions of RAS, the angiotensin type-1 receptor (AT 1 R) and the angiotensin type-2 receptor (AT 2 R), are both present in RPT cells, consistent with a primary role for tubular angiotensins as paracrine substances in the control of renal function. 11,12 The enzymes responsible for the metabolism of Ang II are also highly expressed in the kidney. Aminopeptidase A (APA), a membrane-bound zinc-dependent aminopeptidase, is distributed at the surface of glomerular endothelial and mesangial cells and podocytes and all along the nephron, with highest expression in the RPT. 13,14 As shown in Figure 1, APA preferentially cleaves the N-terminal acidic amino acid (aspartate) from Ang II to generate Ang III, which serves as the rate-limiting step in Ang II metabolism. 15 Aminopeptidase N (APN) is also a membrane-bound, zinc-dependent aminopeptidase and is a major constituent of RPT cell brush border membranes. 16,17 The metabolism of Ang III to Ang IV is mediated by APN, which preferentially releases neutral amino acids from the N-terminal end of oligopeptides. 18 Specific pharmacological inhibitors of APA and APN have been used to elucidate the role of Ang II and Ang III within local tissue RAS. Selective APA inhibitor, EC-33 (3-amino-4-thio-butyl-sulfonic acid, inhibition constant K i ϭ0

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Section: Discussionmentioning

confidence: 99%

Conversion of Renal Angiotensin II to Angiotensin III Is Critical for AT ₂ Receptor–Mediated Natriuresis In Rats

et al. 2008

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“…[29][30][31] In addition to these studies, recent findings suggest that Ang III may be an important agonist, if not the final mediator of some actions of Ang II. 23,[32][33][34] This was clearly shown in the study by Zini et al, 23 in which the use of a specific antagonist of aminopeptidase A, demonstrated that the central action of Ang II on vasopressin secretion in rats is dependent on its prior conversion to Ang III.…”

Section: Ang IIImentioning

confidence: 88%

“…63 This considerable mismatch in the central nervous system, between the distribution of the AT 4 receptor and RAS components, leads us to propose that Ang IV may not be the native ligand for the AT 4 receptor. We have recently identified an alternative ligand for the AT 4 receptor, a decapeptide which is identical to an internal sequence of the sheep (amino acids [30][31][32][33][34][35][36][37][38][39] and human (amino acids 32-41) ␤ globin which we extracted from sheep brain using an AT 4 radioreceptor binding assay and a multistep protein purification procedure. 85 This abundant peptide (approximately 2 nmol of peptide per gram of tissue) and Ang IV share very high affinity for the AT 4 receptor with their binding sites exhibiting very similar affinities for competing ligands and both peptides displayed very similar binding patterns.…”

Section: Ang IVmentioning

confidence: 99%

Bioactive angiotensin peptides

et al. 1998

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Angiotensin II is recognised as the principle active peptide of the renin-angiotensin system, exerting effects on fluid and electrolyte homeostasis, and cardiovascular control including neural and long term trophic effects. However, recent studies indicate that other angiotensin peptides such as angiotensin III, angiotensin II (1-7) and angiotensin IV, may have specific actions. Interestingly, recent work involving angiotensin IV demonstrates that this peptide binds to specific receptors and may be Keywords: angiotensin metabolites; angiotensin III; angiotensin II(1-7); angiotensin IV; globin Bioactive angiotensin peptidesThe renin-angiotensin system (RAS) was initially identified as a circulating humoral system with the effector peptide, angiotensin II (Ang II), generated by an enzymatic cascade. Angiotensinogen, which is synthesized in the liver, is cleaved by renin, a product of the juxtaglomerular cells of the kidney, to form Ang I, which in turn is cleaved by angiotensinconverting enzyme (ACE) to form Ang II. ACE is membrane bound and predominates on the endothelial cells of all vascular beds. Apart from the production of Ang II in plasma, Ang II, renin and ACE have all been described in tissues such as the brain, kidney, adrenal, vasculature, heart and ovaries. This suggests a separate and distinct RAS in these tissues and implies endocrine, paracrine and autocrine roles for Ang II. Actions of Ang IIAng II regulates blood pressure, fluid volume homeostasis and pituitary hormone release via AT 1 and AT 2 receptors located in the kidney, adrenal gland, and the cardiovascular and nervous systems. [2][3][4][5] In the kidney, for instance, Ang II acts on renal vessels, glomeruli, tubules and renomedullary interstitial cells, to alter renal blood flow, glomerular filtration rate and electrolyte reabsorption.6-9 Ang II also acts on the adrenal cortex to stimulate aldosterone secretion and hence renal sodium reabsorption. 10Ang II is a potent vasoconstrictor, acting directly on vascular smooth muscle and indirectly via facilitation of noradrenaline release from sympathetic terminals. 11,12 In the heart, Ang II exerts positive iono- tropic and chronotropic effects and facilitates sympathetic activity. 13Acting on the brain, Ang II induces fluid and salt ingestion, modulates neuroendocrine systems, including vasopressin and corticotropin releasing factor release, and interacts with the autonomic control of the cardiovascular system to influence blood pressure. 3,14,15 In many instances, these effects are complementary to those of the systemic peptide on peripheral target organs. Thus, systematic Ang II affects the brain through AT 1 receptors located in the circumventricular organs, regions with a deficient blood brain barrier. In addition, endogenous neurally derived Ang II appears to act at many central nervous system sites behind the blood brain barrier. [16][17][18] Most of the classical actions of Ang II are mediated via the AT 1 receptor whereas AT 2 receptor stimulation may cause opposing effects. This was o...

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“…[13][14][15] In addition, recent findings suggest that Ang III may be an important agonist, if not the final mediator of Ang II actions in the central nervous system. 7,[16][17][18] This was clearly shown in studies by Zini et al 7 and Reaux et al, 19 in which the use of specific inhibitors of aminopeptidase A, required for the conversion of Ang II to Ang III, blocked Ang IImediated vasopressin secretion and pressor effects in rats. The ability of Ang III to mediate vasopressin release was confirmed by the ability of aminopeptidase A inhibitors to block Ang IImediated increases in the firing rate of vasopressinergic neurones in the supraoptic nucleus.…”

mentioning

confidence: 80%

Bioactive angiotensin peptides: focus on angiotensin IV

Mustafa

Lee

Chai

et al. 2001

J Renin Angiotensin Aldosterone Syst

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The ability of Ang II (1-7) to mediate and oppose Ang II actions has been recently reviewed. [46][47][48][49] Angiotensin 1-9 and ACE2 Recently, a novel ACE-related enzyme (ACE2) has also been discovered, that catalyses carboxypeptidase cleavage of Ang I to generate Ang (1-9), which subsequently serves as a substrate for the generation of Ang II (1-7). ACE2 is found on the endothelium of coronary and intrarenal vessels and renal tubular epithelium, raising the possibility that the formation of Ang II (1-7) may be important in regulating cardiac and renal function. 50,51 Angiotensin IV Angiotensin IV (Ang IV), originally considered to be biologically inactive, has attracted recent attention because of its ability to elicit many biological actions. Ang IV binds with high affinity to a pharmacologically-distinct binding site, designated the AT 4 receptor. 52,53 This binding site shows highest selectivity for Ang IV, with approximately 10-fold lower affinity for Ang III. Affinities for Ang II and [Sar 1 -Ile 8 ] Ang II are markedly lower, while losartan, PD 123177 and CGP 42112A show no activity. [54][55][56][57][58] The AT 4 -receptor has a distinct distribution pattern in the brain, being found in regions associated with cognitive, sensory and motor function in the guinea pig, 55 sheep 59 and monkey. 60 We recently localised the AT 4 receptor in human forebrain, midbrain, and pons, using an iodinated Ang IV analogue, Norleucine 1 -Ang IV (Nle 1 -Ang IV), a more stable analogue of Ang IV with higher affinity for the AT 4receptor. The distribution of the AT 4 -receptor in the human brain was similar to that reported in other species. 61 The AT 4 -receptor is also found in abundance in peripheral tissues, such as the heart, adrenal cortex, kidney, vascular smooth muscle cells and numerous other tissues. 62 REVIEW Figure 1 Schematic representation of the enzymatic events leading to the formation of angiotensin peptides.

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Intracerebroventricularly infused [d-Arg1]angiotensin III, is superior to [d-Asp1]angiotensin II, as a pressor agent in rats

Cited by 33 publications

References 27 publications

Conversion of Renal Angiotensin II to Angiotensin III Is Critical for AT ₂ Receptor–Mediated Natriuresis In Rats

Conversion of Renal Angiotensin II to Angiotensin III Is Critical for AT ₂ Receptor–Mediated Natriuresis In Rats

Bioactive angiotensin peptides

Bioactive angiotensin peptides: focus on angiotensin IV

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Intracerebroventricularly infused [d-Arg1]angiotensin III, is superior to [d-Asp1]angiotensin II, as a pressor agent in rats

Cited by 33 publications

References 27 publications

Conversion of Renal Angiotensin II to Angiotensin III Is Critical for AT 2 Receptor–Mediated Natriuresis In Rats

Conversion of Renal Angiotensin II to Angiotensin III Is Critical for AT 2 Receptor–Mediated Natriuresis In Rats

Bioactive angiotensin peptides

Bioactive angiotensin peptides: focus on angiotensin IV

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Conversion of Renal Angiotensin II to Angiotensin III Is Critical for AT ₂ Receptor–Mediated Natriuresis In Rats

Conversion of Renal Angiotensin II to Angiotensin III Is Critical for AT ₂ Receptor–Mediated Natriuresis In Rats