Merck
  • Home
  • Search Results
  • Endothelin A receptor blocker atrasentan lowers blood pressure by the reduction of nifedipine-sensitive calcium influx in Ren-2 transgenic rats fed a high-salt diet.

Endothelin A receptor blocker atrasentan lowers blood pressure by the reduction of nifedipine-sensitive calcium influx in Ren-2 transgenic rats fed a high-salt diet.

Journal of hypertension (2014-09-26)
Ivana Vaněčková, Zdenka Dobešová, Jaroslav Kuneš, Zdenka Vernerová, Josef Zicha
ABSTRACT

Our previous experiments demonstrated that selective endothelin A (ETA) receptor blockade had antihypertensive effects in Ren-2 transgenic rats (TGRs), but the mechanisms responsible for this change of blood pressure (BP) have not been explored yet. Four-week-old male heterozygous TGRs and their normotensive controls--Hannover Sprague-Dawley (HanSD) rats--were fed high-salt diet (2% NaCl) and were treated with selective ETA receptor blocker atrasentan (5 mg/kg per day) for 8 weeks. At the end of the study, the contribution of principle vasoactive systems was evaluated by the sequential blockade of the renin-angiotensin system (captopril), sympathetic nervous system (pentolinium) and nitric oxide synthase [N-nitro-L-arginine methyl ester (L-NAME)]. The role of calcium influx through L-type voltage-dependent calcium channels in BP maintenance was evaluated using nifedipine. In a separate group of animals, the efficiency of distinct vasodilator systems--prostanoids (blocked by nonselective cyclooxygenase inhibitor indomethacin) and Ca-activated K channels (inhibited by tetraethylammonium)--was also analyzed. Atrasentan attenuated the development of hypertension in heterozygous TGRs, but had no effects in Hannover Sprague-Dawley rats. Moreover, atrasentan moderately attenuated renin-angiotensin system-dependent vasoconstriction, whereas it had no effect on sympathetic vasoconstriction. The nifedipine-sensitive BP component was markedly decreased by atrasentan treatment. In contrast, vasodilatation mediated by nitric oxide, endogenous prostanoids or Ca-activated K channels was reduced in atrasentan-treated TGRs, indicating the absence of compensatory augmentation of endothelin B receptor-mediated vasodilation in these animals. BP-lowering effect of chronic atrasentan treatment in TGRs was mainly caused by reduced Ca influx through L-type voltage-dependent calcium channels due to missing ETA receptor-dependent vasoconstriction and attenuated angiotensin II-dependent vasoconstriction.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Fluorescein 5(6)-isothiocyanate, BioReagent, suitable for fluorescence, mixture of 2 components, ≥90% (HPLC)
Supelco
Acetone solution, certified reference material, 2000 μg/mL in methanol: water (9:1)
Trolamine impurity A, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Fluorescein 5(6)-isothiocyanate, ≥90% (HPLC)
Sigma-Aldrich
Ethanolamine, liquid, BioReagent, suitable for cell culture, ≥98%
Sigma-Aldrich
Ethanolamine, ≥98%
Sigma-Aldrich
Acetone, suitable for HPLC, ≥99.9%
Sigma-Aldrich
Ethanolamine, ACS reagent, ≥99.0%
Sigma-Aldrich
Acetone, purum, ≥99.0% (GC)
Sigma-Aldrich
Ethanolamine, ≥99%
Sigma-Aldrich
Fluorescein isothiocyanate isomer I, ≥97.5% (HPLC)
Sigma-Aldrich
Ethanolamine, purified by redistillation, ≥99.5%
Supelco
Ethanolamine, analytical standard
Supelco
Aucubin, analytical standard
Sigma-Aldrich
Ethanolamine, puriss. p.a., ACS reagent, ≥99.0% (GC/NT)
Sigma-Aldrich
Acetone, suitable for HPLC, ≥99.8%
Sigma-Aldrich
Acetone, suitable for HPLC, ≥99.9%
Sigma-Aldrich
Acetone, HPLC Plus, for HPLC, GC, and residue analysis, ≥99.9%
Sigma-Aldrich
Acetone, ACS reagent, ≥99.5%
Sigma-Aldrich
Acetone, puriss., meets analytical specification of Ph. Eur., BP, NF, ≥99% (GC)
Sigma-Aldrich
Acetone, puriss. p.a., ACS reagent, reag. ISO, reag. Ph. Eur., ≥99.5% (GC)
Sigma-Aldrich
Fluorescein isothiocyanate isomer I, ≥97.5% (HPLC)
Sigma-Aldrich
Fluorescein isothiocyanate isomer I, suitable for protein labeling, ≥90% (HPLC), powder
SAFC
Ethanolamine
Aucubin, primary reference standard