Cajaninstilbene Acid Relaxes Rat Renal Arteries: Roles of Ca2+ Antagonism and Protein Kinase C-Dependent Mechanism

Abstract

Cajaninstilbene acid (CSA) is a major active component present in the leaves of Cajanus cajan (L.) Millsp. The present study explores the underlying cellular mechanisms for CSA-induced relaxation in rat renal arteries. Vascular reactivity was examined in arterial rings that were suspended in a Multi Myograph System and the expression of signaling proteins was assessed by Western blotting method. CSA (0.1–10 µM) produced relaxations in rings pre-contracted by phenylephrine, serotonin, 9, 11-dideoxy-9α, 11α-epoxymethanoprostaglandin F2α (U46619), and 60 mM KCl. CSA-induced relaxations did not show difference between genders and were unaffected by endothelium denudation, nor by treatment with NG-nitro-L-arginine methyl ester, indomethacin, ICI-182780, tetraethylammonium ion, BaCl2, glibenclamide, 4-aminopyridine or propranolol. CSA reduced contraction induced by CaCl2 (0.01–5 mM) in Ca2+-free 60 mM KCl solution and by 30 nM (−)-Bay K8644 in 15 mM KCl solution. CSA inhibited 60 mM KCl-induced Ca2+ influx in smooth muscle of renal arteries. In addition, CSA inhibited contraction evoked by phorbol 12-myristate 13-acetate (PMA, protein kinase C agonist) in Ca2+-free Krebs solution. Moreover, CSA reduced the U46619- and PMA-induced phosphorylation of myosin light chain (MLC) at Ser19 and myosin phosphatase target subunit 1 (MYPT1) at Thr853 which was associated with vasoconstriction. CSA also lowered the phosphorylation of protein kinase C (PKCδ) at Thr505. In summary, the present results suggest that CSA relaxes renal arteries in vitro via multiple cellular mechanisms involving partial inhibition of calcium entry via nifedipine-sensitive calcium channels, protein kinase C and Rho kinase.

Mechanisms of U46619‐induced contraction in mouse intrarenal artery

“…Furthermore, the vasocontraction was greatly attenuated by the PKCδ inhibitor rottlerin, while the PKCβ inhibitor hispidin, or PKCζ pseudosubstrate inhibitor PKC‐PS showed no effect. A previous study shows that CSA relaxes rat renal arteries by reducing U46619‐induced phosphorylation of PKCδ, which aligns with our findings that PKCδ plays an important role in U46619‐induced renal contraction …”

Cajaninstilbene Acid Prevents Corticosterone-Induced Apoptosis in PC12 Cells by Inhibiting the Mitochondrial Apoptotic Pathway

“…This increase in intracellular Ca 2+ can induce mitochondrial dysfunction via the activation of mPTPs, which results in a cascade of reactions that lead to cell death [30,31,32]. Moreover, the observed ∆Ψm is thought to be mediated by the opening of mPTPs [31,32,33], and reductions in ∆Ψm that accompany early apoptosis have been reported under different conditions [31,32,34]. We found that intracellular Ca 2+ concentrations were significantly higher in cells treated with CORT, which also caused pathological and abnormal opening of mPTPs and disruptions of ∆Ψm in PC12 cells (Figs.…”

Inhibitory effect of rhynchophylline on contraction of cerebral arterioles to endothelin 1: Role of rho kinase

“…Following washing three times with Krebs buffer and being equilibrated for 15 min, the arteries were contracted with KCl (60 mM), Bay K8644 (3 Â 10 À 7 M) or ET-1 (2À5 Â 10 À 8 M). Before the arteries were constricted by Bay K8644 (3 Â 10 À 7 M), 30 mM KCl was added into the solution to enlarge the constriction caused by Bay K8644 (3 Â 10 À 7 M) (Zhang et al, 2012). After the contraction was stabilized, the effects of Rhy were examined.…”