Secretoneurin facilitates endothelium-dependent relaxations in porcine coronary arteries

Abstract

Chan CK, Vanhoutte PM. Secretoneurin facilitates endotheliumdependent relaxations in porcine coronary arteries. Am J Physiol Heart Circ Physiol 300: H1159 -H1165, 2011. First published February 4, 2011 doi:10.1152/ajpheart.00519.2010.-Secretoneurin enhances the adhesion and transendothelial migration properties of monocytes and is a part of the peptide family encoded by the secretogranin II gene. The expression of the secretogranin II gene is upregulated in senescent endothelium. The present study was designed to examine the effects of secretoneurin on endotheliumdependent responsiveness. Isometric tension was measured in rings (with or without endothelium) of porcine coronary arteries. Secretoneurin did not induce contraction of quiescent or contracted rings. In preparations contracted by U-46619, relaxation was observed with high concentrations of the peptide. This relaxation was endothelium dependent and reduced by the nitric oxide synthase inhibitor N -nitro-L-arginine methyl ester (L-NAME). It was abolished when the preparations were incubated with L-NAME in combination with the cyclooxygenase inhibitor indomethacin. The relaxation was not affected by the combination of 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole (TRAM-34) and 6,12,19,20,25,26-hexahydro-5,27:13,18:21,24-trietheno-11,7-etheno-7H-dibenzo[b,m] [1,5,12,16]tetraazacyclotricosine-5,13-diiumditrifluoroacetate hydrate (UCL 1684), which abrogates endothelium-dependent hyperpolarizations. These results indicate that secretoneurin acutely induces relaxation through the activation of endothelial nitric oxide synthase (eNOS) and cyclooxygenase, with nitric oxide playing the dominant role. Prolonged (24 h) incubation with physiological concentrations of secretoneurin enhanced the relaxations to bradykinin and to the calcium ionophore A-23187, but this difference was not observed in preparations incubated with L-NAME or the calmodulin antagonist calmidazolium. Under these conditions, the relaxation to sodium nitroprusside remained unchanged. Incubation with secretoneurin significantly augmented the expression of eNOS and calmodulin as well as the dimerization of eNOS in cultures of porcine coronary arterial endothelial cells. These observations suggest that secretoneurin not only acutely causes but also, upon prolonged exposure, enhances endotheliumdependent relaxations. nitric oxide; secretogranin II ENDOTHELIUM-DEPENDENT, instantaneous decreases in vascular tone (7a) are mediated by nitric oxide in large arteries in response to increased shear stress and other stimuli. Nitric oxide also prevents smooth muscle proliferation as well as platelet aggregation (32,33). Under normal conditions, endothelium-derived nitric oxide is produced by the endothelial isoform of nitric oxide synthase (eNOS) (1). Endothelial cells also contain cyclooxygenase(s) transforming arachidonic acid into endoperoxides, which are metabolized further into vasoactive prostanoids, in particular, the vasodilator prostacyclin (21).In senescent cultured porcine coronary arterial endot...

Thirty Years of Saying NO

“…Modified from Zhao et al 29 (Copyright ©2015, The Authors). α indicates α-adrenergic receptor; 5HT, serotonin (5-hydroxytryptamine); 5HT1d, serotoninergic (5 hydroxytryptamine) receptor 1D subtypes; ACh, acetylcholine; Ang 1-7 , angiotensin [1][2][3][4][5][6][7] ; AdipoR, adiponectin receptor; AVP, arginine vasopressin; B, kinin receptor; E, epinephrine; EP4, prostaglandin E 2 -receptor 4; ER, nongenomic estrogen receptor; ET, endothelin-1; ETb, endothelin-receptor B subtypes; GLP, glucagon-like peptide-1, glucagon-like peptide receptor; GPR55, G-protein-coupled receptor 55; H, histaminergic receptor; HDL, high-density lipoproteins; IP, prostacyclin receptor; IR 1 , insulin receptor; M, muscarinic receptor; Mas, Mas receptor; MC, melanocortin receptor; NE, norepinephrine; P, purinergic receptor; PAR, protease activated receptor; PGE 2 in a nongenomic manner on G-protein-coupled receptors), glucagon-like peptide-1, high-density lipoproteins (HDL; associating with sphingosine 1 -phosphate), insulin (by activating the PI3K/Akt pathway), irisin 52 (an autacoid/hormone secreted by myocytes), melanocortin (α-melanocyte-stimulating hormone), oxytocin, secretoneurin, 79 and vasopressin. 15 Likewise, aggregating platelets (Figure 2) release adenine nucleotides (in particular, ADP) and 5-hydroxytryptamine (serotonin), which induce endothelium-dependent relaxations.…”

“…15 Prolonged incubation with secretoneurin potentiates endothelium-dependent relaxations in isolated arteries. 79 Thyroid hormone, acting on thyroid hormone receptors (TRα 1 ) also upregulates eNOS, augments the endothelial production of NO, and facilitates endothelium-dependent relaxations. 15 …”

iTRAQ‑based quantitative proteomics analysis of the potential application of secretoneurin gene therapy for cardiac hypertrophy induced by DL‑isoproterenol hydrochloride in mice

“…However, subsequent studies demonstrated that it could act as a potential protector against cardiovascular events (6,13,35). SN plays a protective role in myocardial ischemia and heart failure (36,37) by inducing angiogenesis and postnatal vasculogenesis (13,38). However, to the best of our knowledge, the regulation of SN in cardiac…”

Acute activation of endothelial AMPK surprisingly inhibits endothelium‐dependent hyperpolarization‐like relaxations in rat mesenteric arteries

“…To examine the direct effects of A769662 on vascular smooth muscle, arterial rings without endothelium, treated with l ‐NAME and indomethacin, were incubated (for 40 min) in the absence or presence of different pharmacological agents (alone or in combination) {including: A769662 [to directly compare the effects of A769662 on vascular smooth muscle to those on relaxations to other vasodilators (including ACh, SKA‐31, potassium ions and levcromakalim); the same concentration (10 −4 M) of A769662 (for which the present results demonstrate AMPK activation) was used throughout the study], nifedipine [10 −6 M; blocker of voltage‐operated calcium channel (VOCC) (Chan & Vanhoutte, )] and Y27632 [10 −5 M; inhibitor of Rho kinase (Chan, Mak, Man, & Vanhoutte, )]} before exposing them to gradually increasing cumulative concentrations of phenylephrine (10 −9 to 10 −5 M) or of the calcium ionophore A23187 (3 × 10 −6 M). In order to examine the effect of A769662 on calcium release from intracellular stores, rings were incubated with calcium‐free solution (omitting CaCl 2 from control solution) for 5 min before the addition of phenylephrine (Hisayama, Takayanagi, & Okamoto, ; Low, Kwan, & Daniel, ).…”