Renin-Angiotensin System

The renin-angiotensin system (RAS) is considered one of the key modulators of blood volume/pressure, and cardiac and vascular function. The RASpathway is common to many tissues. However, the most notable occurrence of this pathway is in the kidney. The RAS pathway is a cascadebeginning with the production of angiotensinogen in the liver. Sympathetic stimulation of β1-adrenoceptors, renal artery hypotension, anddecreased sodium in the distal tubules stimulate the release of renin by the kidney. Renin hydrolyzes angiotensinogen to yield the relatively inactiveprecursor angiotensin I. Angiotensin I is cleaved by angiotensin converting enzyme (ACE) to yield the more active angiotensin II (ATII). Angiotensin IIthen acts on ATI receptors to stimulate systemic vasoconstriction and expression of plasminogen activator inhibitor (PAI). Conversely, angiotensin IIbinding to ATII receptors may cause vasodilation and apoptosis. ATII acts on the adrenal cortex to stimulate aldosterone production, which in turnstimulates sodium resorption from the distal tubules.

Angiotensin I human acetate hydrate

Hypertensin IAsp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-LeuC62H89N17O14 · xC2H4O2 · yH2O FW 1296.48 EC No. 2158049≥90% (HPLC)Angiotensin I is a putative neurotransmitter. It is the precursor ofangiotensin II and of angiotensin fragment 1‑7, which are thehormones involved in regulation of fluid volume and the release ofaldosterone.mol wt 1296 Da by calculation (Average Mass)Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu-OH · 2CH3COOH · 6H2OB

A9650-1MG 1 mg

A9650-5MG 5 mg

A9650-10MG 10 mg

A9650-50MG 50 mg

Angiotensin II human acetate

Hypertensin IIAsp-Arg-Val-Tyr-Ile-His-Pro-PheC50H71N13O12 · xH2O FW 1046.18 (Anh) [68521‑88‑0] ECNo. 2061823 BRN 3929368~95% (HPLC), powderAngiotensin (Ang) II is important in regulating cardiovascular hemo-dynamics and cardiovascular structure. Most of the known effects ofAng II in adult tissues are attributable to the angiotensin II type I (AT1)receptor. The AT1 and AT2 receptors have differential pharmacologicaland biochemical properties and appear to exert opposite effects interms of cardiovascular hemodynamics and cell growth. In addition,the renin-angiotensin and nitric oxide-generating systems appear to

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interract in the regulation of cardiovascular function. Ang II stimulatesangiogenesis and increases microvessel density. In nature, angiotensinII is produced by the action of angiotensin converting enzyme onangiotensinogen; the C-terminal-His-Leu is cleaved.Free of trifluoracetic acidPeptide content not less than 75%Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-OH.2CH3COOH.H2OB

A9525-1MG 1 mg

A9525-5X1MG 5 × 1 mg

A9525-5MG 5 mg

A9525-10MG 10 mg

A9525-50MG 50 mg

Angiotensinogen from human plasma

Hypertensinogen; Renin substrate[11002‑13‑4]≥80% (SDS-PAGE), lyophilized powderLyophilized powder containing sodium phosphate buffer salt, pH 6.8.Package size based on protein content.

Protein determined by A1%280

IB

A2562-.1MG 0.1 mg

Angiotensinogen from porcine plasma

Angiotensinogen from hog plasma; Hypertensinogen; Renin substrate[64315‑16‑8]lyophilized powder, activity: 1,500‑3,000 units/g proteinLyophilized powder containing sodium citrate.suitable for measuring renin by RIAcomposition

Protein ~65% (modified Warburg-Christian)One unit will yield 1.0 nmole of angiotensin I in the presence of reninat pH 6.0 at 37 °C measured by RIA.B

A2283-.1UN 0.1 unit

A2283-1UN 1 unit

Angiotensin Converting Enzyme from rabbit lung

ACE; Peptidyl-dipeptidase A; Peptidyldipeptide Hydrolase[9015‑82‑1] E.C. 3.4.15.1lyophilized powder, activity: 2‑6 units/mg protein (modifiedWarburg-Christian)Removes C-terminal dipeptides from susceptible substrates, e.g.,angiotensin I and bradykinin.May contain traces of sodium chloride.One unit will produce 1.0 μmole of hippuric acid from Hippuryl-His-Leuper min in 50 mM HEPES and 300 mM NaCl at pH 8.3 at 37 °C.B

A6778-.1UN 0.1 unit

A6778-.25UN 0.25 unit

A6778-1UN 1 unit

A6778-2UN 2 units

A6778-5UN 5 units

Angiotensin Converting Enzyme from porcine kidney

ACE; Peptidyl-dipeptidase A[9015‑82‑1] E.C. 3.4.15.1lyophilized powder, activity: ≥10 units/mg protein (Bradford)Removes C-terminal dipeptides from susceptible substrates, e.g.,angiotensin I and bradykinin.ACE is a monomer with molecular weight of ~170 kDapH range for activity: 7‑8.5Temperature optimum: 37 °CZinc is required for activityInhibitors: captopril, enalaprilat, lisinopril etc. (1‑10 μM)

Lyophilized powder containing Tris buffer salts.One unit will produce 1.0 μmole of hippuric acid from hippuryl-His-Leuper min in 100 mM Tris-HCl, 300 mM NaCl and 10 μM ZnCl2 at pH 8.3at 37 °C.B

A2580-.1UN 0.1 unit

A2580-.5UN 0.5 unit

A2580-1UN 1 unit

Activation peptide

Signal Active site

Peptidase S1

Disulfides

Chymase

N-Linked Glycans

........

........

10 20 30 40 50 60 70 80 90 100 110 120 130 140 150 160 170 180 190 200 210 220 230 240

(Human)

Chymase human

Mast cell protease I[97501‑92‑3] E.C. 3.4.21.39activity: ≥30 units/mg protein, Isolated from human mast cellsChymase plays an important role in generating angiotensin II inresponse to injury of vascular tissues. Inhibition of chymase may beuseful for preventing vascular proliferation in grafted vessels. Cardiacchymase has been shown to participate directly in the pathophysiologicstate after myocardial infarction in hamsters. Human chymaseselectively converts Big Endothelin 1 to the 31 amino acid lengthpeptide Endothelin 1 [ET-1(1‑31)]. ET-1(1‑31) increases Ca2+ concen-tration and produces NO in endothelial cells through Big Endothelin.Chymase may contribute to development of induced dermatitis bypromoting eosinophile infiltration. In addition chymase is reported todegrade the ECM, and processes procollagenase, inflammatorycytokines, and other bioactive peptides. Chymase inhibitors may findapplications for the treatment of cardiovascular as well as inflammatorydiseases.Chymase is a 137 amino acid, cathepsin G-like, serine proteinase foundprimarily in mast cells. Mast cell chymase is particularly abundant in thedermis of human skin. Human mast cell chymase was found to beessentially identical to cardiac chymase. It has a molecular mass ofapproximately 30 kDa.Preferential cleavage: Phe-|-Xaa > Tyr-|-Xaa > Trp-|-Xaa > Leu-|-Xaa.

IN B DRY ICE

C9612-50UG 50 μg

Angiotensin II human (continued)

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Plasma Derived Proteins and EnzymesRenin-Angiotensin System

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Kallikrein from human plasma

Kininogenase; Kininogenin[9001‑01‑8] E.C. 3.4.21.34buffered aqueous solution, activity: ≥10 units/mg proteinSolution in 20 mM Tris-HCl, pH 7.8 with 100 mM NaCl.One unit will hydrolyze 1.0 μmole of Nα-benzoyl-L-arginine ethyl ester(BAEE) to Nα-benzoyl-L-arginine and ethanol per min at pH 8.7 at 25°C.

IB DRY ICE

K2638-50UG 50 μg

Kininogen high molecular weight, Two Chain fromhuman plasma

lyophilized powderHigh molecular weight kininogen, two chain, is a participant in contactphase activation of the intrinsic blood coagulation cascade that forms asubstrate on which blood factor XI is held in proximity to factor XIIallowing reciprocal activation of the two factors. It is also involved inthe activation of prekallikrein. High molecular weight kininogen bindsto proteoglycans on the surface of platelets, endothelial cells, andother cell types. Domain 5 of high molecular weight kininogen inhibitsplatelet aggregation and angiogenesis.

Lyophilized from 4 mM sodium acetate, pH 5.3, 0.15 M NaClPrepared by kallikrein digestion of human kininogen. Purified toremove kallikrein and kinin.Package size based on protein content

IB

K1632-.1MG 0.1 mg

Kininogen, low molecular weight from human plasma

LMW kininogen>95% (SDS-PAGE), lyophilized powderLMW kininogen is a major extracellular cysteine proteinase inhibitor.Tissue kallikrein releases bradykinin, a potent bronchoconstrictor andvasoactive agent, from both HMW and LMY kininogen.

Lyophilized from a solution in sodium acetate and sodium chloride.mol wt 64 kDaOne unit will hydrolyze 1.0 μmole of Nα-benzoyl-L-arginine ethyl ester(BAEE) to Nα-benzoyl-L-arginine and ethanol per min at pH 8.7 at25°C.

IB DRY ICE

K3628-.1MG 0.1 mg

Active Site

N-Linked Glycan

Disulfides

Signal Peptide

Renin(Human Sequence)

Activation peptide

....

....

....

....

20 40 60 80 100 120 140 160 180 200 220 240 260 280 300 320 340 360 380 400

Renin human

E.C. 3.4.23.15recombinant, expressed in HEK 293 cells, activity: ≥90 unit/μgprotein, ≥99% (SDS-PAGE)Prorenin granules are stored within modified smooth muscle cellsadjacent to the distal tubule and the afferent arteriole. Prorenin isreleased into the blood from the juxtaglomerular cells in the wall of theafferent arteriole. Prorenin is then hydrolyzed by plasma kallekrein toproduce active renin.Expressed in HEK cells as prorenin. The prorenin is activated to reninusing trypsin and re-purified.One unit will produce one fluorescent unit from the hydrolysis of ReninSubstrate I (Arg-Glu(EDANS)-Ile-His-Pro-Phe-His-Leu-Val-Ile-His-Thr-Lys(dabcyl)-Arg) at 37 °C at pH 8.0N B DRY ICE

R2779-10UG 10 μg

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