Vasorelaxant effect of trans‐4‐chloro‐β‐nitrostyrene, a synthetic nitroderivative, in rat thoracic aorta

Abstract

Previously, we showed that 1‐nitro‐2‐phenylethene, a nitrostyrene derivative of 1‐nitro‐2‐phenylethane, induced vasorelaxant effects in rat aorta preparations. Here, we studied mechanisms underlying the vasorelaxant effects of its structural analog, trans‐4‐chloro‐β‐nitrostyrene (T4CN), in rat aortic rings. Increasing concentrations of T4CN (0.54‐544.69 µm) fully and similarly relaxed contractions induced by phenylephrine (PHE, 1 µm) or KCl (60 mm) in endothelium‐intact aortic rings with IC50 values of 66.74 [59.66–89.04] and 79.41 [39.92–158.01] µm, respectively. In both electromechanical and pharmacomechanical couplings, the vasorelaxant effects of T4CN remained unaltered by endothelium removal, as evidenced by the IC50 values (108.35 [56.49–207.78] and 65.92 [39.72–109.40] µm, respectively). Pretreatment of endothelium‐intact preparations with L‐NAME, ODQ, glibenclamide, or TEA did not change the vasorelaxant effect of T4CN. Under Ca2+‐free conditions, T4CN significantly reduced the phasic contractions induced by caffeine or PHE, as well as the contractions due to exogenous CaCl2 in aortic preparations stimulated with PHE (in the presence of verapamil). These results suggest that in rat aortic rings, T4CN induced vasorelaxation independently from the activation of soluble guanylate cyclase/cGMP pathway, an effect that may be related to the electrophilicity of the substituted chloro‐nitrostyrene. This vasorelaxation seems to involve inhibition of both calcium influx from the extracellular milieu and calcium mobilization from intracellular stores mediated by IP3 receptors and by ryanodine‐sensitive Ca2+ channels.

Activation of the Mas receptors by AVE0991 and MrgD receptor using alamandine to limit the deleterious effects of Ang II‐induced hypertension

“…Vascular contractile and relaxation responses were evaluated with phenylephrine (Phe, 3 × 10 −9 –10 −4 mol/L) and acetylcholine (Ach, 10 −9 –10 −5 mol/L), respectively (Appendix S1). 25 …”

Verapamil downregulates iron uptake and upregulates divalent metal transporter 1 expression in H9C2 cardiomyocytes

“…TRIzol reagent and Superscript II reverse transcriptase were obtained from Invitrogen Corp., Carlsbad, CA, USA, and Bradford assay kit from Bio-Rad, Hercules, CA, USA. Verapamil (Sigma) was dissolved in distilled water and then with KHS (Krebs-Henseleit solution) to achieve desired concentration [17]. The Health Department of Shanghai Government and the Animal Research Ethics Committee of Fudan University approved the experimental procedures of this study (Permit Number: FU-P 31271132).…”

Mechanisms underlying the vasorelaxant effect of hydrogen sulfide on human saphenous vein

“…When a stable and sustained contraction (approximately 15-20 min) was achieved, each subsequent dose of NaHS was added only after the previous one reached its relaxing plateau or after 20 min if no response was obtained. Acetylcholine (1 µM) was used to test endothelial layer integrity [17,18].…”

“…This effect seems to be mediated through the activation of NO pathway and prostacyclin in addition to direct or indirect action on different K + and Ca 2+ channels (Figure 7). After the first study exploring relaxing effect of H 2 S reported its effect on rat portal vein [18,20], the latter investigations were mainly focused on the arteries. Also, there are only few studies obtained on the human vessels [6,14,21].…”