Merck
  • Home
  • Search Results
  • Cardiovascular and pharmacological implications of haem-deficient NO-unresponsive soluble guanylate cyclase knock-in mice.

Cardiovascular and pharmacological implications of haem-deficient NO-unresponsive soluble guanylate cyclase knock-in mice.

Nature communications (2015-10-08)
Robrecht Thoonen, Anje Cauwels, Kelly Decaluwe, Sandra Geschka, Robert E Tainsh, Joris Delanghe, Tino Hochepied, Lode De Cauwer, Elke Rogge, Sofie Voet, Patrick Sips, Richard H Karas, Kenneth D Bloch, Marnik Vuylsteke, Johannes-Peter Stasch, Johan Van de Voorde, Emmanuel S Buys, Peter Brouckaert
ABSTRACT

Oxidative stress, a central mediator of cardiovascular disease, results in loss of the prosthetic haem group of soluble guanylate cyclase (sGC), preventing its activation by nitric oxide (NO). Here we introduce Apo-sGC mice expressing haem-free sGC. Apo-sGC mice are viable and develop hypertension. The haemodynamic effects of NO are abolished, but those of the sGC activator cinaciguat are enhanced in apo-sGC mice, suggesting that the effects of NO on smooth muscle relaxation, blood pressure regulation and inhibition of platelet aggregation require sGC activation by NO. Tumour necrosis factor (TNF)-induced hypotension and mortality are preserved in apo-sGC mice, indicating that pathways other than sGC signalling mediate the cardiovascular collapse in shock. Apo-sGC mice allow for differentiation between sGC-dependent and -independent NO effects and between haem-dependent and -independent sGC effects. Apo-sGC mice represent a unique experimental platform to study the in vivo consequences of sGC oxidation and the therapeutic potential of sGC activators.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Sodium fluoride, BioReagent, suitable for insect cell culture, ≥99%
Sigma-Aldrich
Anti-Guanylyl Cyclase β1 (ER-19) antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
Calcium chloride, anhydrous, BioReagent, suitable for insect cell culture, suitable for plant cell culture, ≥96.0%
Sigma-Aldrich
Ethylenediaminetetraacetic acid, ACS reagent, 99.4-100.6%, powder
Sigma-Aldrich
Calcium chloride, meets USP testing specifications
Sigma-Aldrich
Anti-Guanylyl Cyclase α1 antibody produced in rabbit, IgG fraction of antiserum, buffered aqueous solution
Sigma-Aldrich
Sodium citrate tribasic dihydrate, ACS reagent, ≥99.0%
Sigma-Aldrich
Sodium citrate tribasic dihydrate, for molecular biology, ≥99%
Sigma-Aldrich
Sodium citrate tribasic dihydrate, ≥98%
Sigma-Aldrich
Ethylenediaminetetraacetic acid, purified grade, ≥98.5%, powder
Sigma-Aldrich
Ethylenediaminetetraacetic acid, anhydrous, crystalline, BioReagent, suitable for cell culture
Sigma-Aldrich
Ethylenediaminetetraacetic acid, BioUltra, anhydrous, ≥99% (titration)
Sigma-Aldrich
Sodium citrate tribasic dihydrate, BioXtra, ≥99.0% (titration)
SAFC
L-Glutamine
Sigma-Aldrich
Sodium citrate tribasic dihydrate, puriss. p.a., ACS reagent, ≥99.0% (NT)
Sigma-Aldrich
Calcium chloride solution, BioUltra, for molecular biology, ~1 M in H2O
Sigma-Aldrich
Ethanol, purum, secunda spirit, denaturated with 2% 2-butanone and 0.5% 4-methyl-2-pentanone, S15, ~96% (based on denaturant-free substance)
Sigma-Aldrich
L-Glutamine, BioUltra, ≥99.5% (NT)
Sigma-Aldrich
L-Glutamine, γ-irradiated, BioXtra, suitable for cell culture
Sigma-Aldrich
L-Glutamine, meets USP testing specifications, suitable for cell culture, 99.0-101.0%, from non-animal source
Sigma-Aldrich
L-Glutamine, ReagentPlus®, ≥99% (HPLC)
Sigma-Aldrich
Guanosine 3′,5′-cyclic monophosphate sodium salt, ≥99% (HPLC), powder
Sigma-Aldrich
Glycerol, FCC, FG
Sigma-Aldrich
Calcium chloride, anhydrous, powder, 99.99% trace metals basis
Sigma-Aldrich
Sodium citrate dihydrate, ≥99%, FG
Sigma-Aldrich
Ethylenediaminetetraacetic acid solution, 0.02% in DPBS (0.5 mM), sterile-filtered, BioReagent, suitable for cell culture
Sigma-Aldrich
Glycerol, BioReagent, suitable for cell culture, suitable for insect cell culture, suitable for electrophoresis, ≥99% (GC)
Sigma-Aldrich
Glycerol, for molecular biology, ≥99.0%
Sigma-Aldrich
Glycerol, BioXtra, ≥99% (GC)
Sigma-Aldrich
Glycerol, ≥99.5%