MilliporeSigma
  • Home
  • Search Results
  • Different compartmentation of responses to brain natriuretic peptide and C-type natriuretic peptide in failing rat ventricle.

Different compartmentation of responses to brain natriuretic peptide and C-type natriuretic peptide in failing rat ventricle.

The Journal of pharmacology and experimental therapeutics (2014-07-16)
Lise Román Moltzau, Jan Magnus Aronsen, Silja Meier, Jonas Skogestad, Øivind Ørstavik, Gustav B Lothe, Ivar Sjaastad, Tor Skomedal, Jan-Bjørn Osnes, Finn Olav Levy, Eirik Qvigstad
ABSTRACT

We previously found a negative inotropic (NIR) and positive lusitropic response (LR) to C-type natriuretic peptide (CNP) in the failing heart ventricle. In this study, we investigated and compared the functional responses to the natriuretic peptides (NPs), brain (BNP) and C-type natriuretic peptide (CNP), and relate them to cGMP regulation and effects on downstream targets. Experiments were conducted in left ventricular muscle strips and ventricular cardiomyocytes from Wistar rats with heart failure 6 weeks after myocardial infarction. As opposed to CNP, BNP did not cause an NIR or LR, despite increasing cGMP levels. The BNP-induced cGMP elevation was mainly and markedly regulated by phosphodiesterase (PDE) 2 and was only marginally increased by PDE3 or PDE5 inhibition. Combined PDE2, -3, and -5 inhibition failed to reveal any functional responses to BNP, despite an extensive cGMP elevation. BNP decreased, whereas CNP increased, the amplitude of the Ca(2+) transient. BNP did not increase phospholamban (PLB) or troponin I (TnI) phosphorylation, Ca(2+) extrusion rate constant, or sarcoplasmatic reticulum Ca(2+) load, whereas CNP did. Both BNP and CNP reduced the peak of the L-type Ca(2+) current. Cyclic GMP elevations by BNP and CNP in cardiomyocytes were additive, and the presence of BNP did not alter the NIR to CNP or the CNP-induced PLB and TnI phosphorylation. However, a small increase in the LR to maximal CNP was observed in the presence of BNP. In conclusion, different responses to cGMP generated by BNP and CNP suggest different compartmentation of the cGMP signal and different roles of the two NPs in the failing heart.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Cilostamide, phosphodiesterase inhibitor
Sigma-Aldrich
Prazosin hydrochloride, ≥99.0% (HPLC)
Sigma-Aldrich
Guanosine 3′,5′-cyclic monophosphate sodium salt, ≥99% (HPLC), powder
Sigma-Aldrich
Atropine sulfate salt monohydrate, ≥97% (TLC), crystalline
USP
Prazosin hydrochloride, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
Timolol maleate salt, ≥98% (TLC), powder
Atropine sulfate, European Pharmacopoeia (EP) Reference Standard
Timolol for system suitability, European Pharmacopoeia (EP) Reference Standard
USP
Atropine sulfate, United States Pharmacopeia (USP) Reference Standard
Prazosin hydrochloride, European Pharmacopoeia (EP) Reference Standard
Supelco
Atropine Sulfate, Pharmaceutical Secondary Standard; Certified Reference Material
Isoflurane, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Guanosine 3′,5′-cyclic monophosphate, ≥98% (HPLC), powder
Sildenafil citrate, European Pharmacopoeia (EP) Reference Standard
Timolol maleate, European Pharmacopoeia (EP) Reference Standard