Mechanism of Ca²⁺release and entry during contraction elicited by norepinephrine in rat resistance arteries

Abstract

Lagaud, G. J. L., V. Randriamboavonjy, G. Roul, J. C. Stoclet, and R. Andriantsitohaina. Mechanism of Ca 2ϩ release and entry during contraction elicited by norepinephrine in rat resistance arteries. Am. J. Physiol. 276 (Heart Circ. Physiol. 45): H300-H308, 1999.-The intracellular Ca 2ϩ stores and the mechanisms of Ca 2ϩ entry produced by norepinephrine (NE) were investigated in small mesenteric resistance arteries of the rat. In Ca 2ϩ -free medium, NE (10 µM) elicited a transient increase in both intracellular free Ca 2ϩ concentration ([Ca 2ϩ ] i ) and tension that were both drastically reduced by caffeine and only partially reduced by the two sarco(endo)plasmic reticulum Ca 2ϩ -ATPase (SERCA) blockers thapsigargin and cyclopiazonic acid, despite the presence of SERCA2a and SERCA2b isoforms in the medial smooth muscle layer of the artery. After depletion of intracellular Ca 2ϩ stores with 10 µM NE, addition of exogenous CaCl 2 (2.5 mM) produced large and sustained increases in both [Ca 2ϩ ] i and contraction of the arteries provided that the agonist was continuously present. In these conditions, the responses to CaCl 2 were inhibited by the voltage-dependent Ca 2ϩ entry blocker nitrendipine (1 µM), the putative inhibitor of receptoroperated Ca 2ϩ entry SKF-96365 (30 µM), and NiCl 2 (1 mM). The inhibition produced by SKF-96365 and NiCl 2 was greater than that of nitrendipine. Also, the responses to CaCl 2 were greatly reduced or abolished in the presence of the Na ϩ /Ca 2ϩ exchanger inhibitors 1,3-dimethyl-2-thiourea, 3Ј,4Ј-dichlorobenzamil, MgCl 2 , and amiloride or after omission of NaCl in the medium. Also, protein kinase C inhibitors, calphostin C and staurosporine, and tyrosine kinase inhibitors, genistein and tyrphostin 23, both reduced the responses to CaCl 2 . The inhibitory effect of protein kinase C inhibitor and tyrosine kinase were additive. These results suggest that NE releases Ca 2ϩ from intracellular stores that are caffeine sensitive and partially sensitive to SERCA inhibitors. They indicate that in addition to Ca 2ϩ influx via nitrendipine-sensitive and SKF-96365-sensitive channels, Na ϩ /Ca 2ϩ exchanger participates in the CaCl 2 -induced contraction produced in NE-exposed vessels. The pathway leading to Ca 2ϩ entry probably involves tyrosine kinase and protein kinase C. All the above mechanisms require ongoing receptor stimulation. calcium entry; intracellular calcium stores IT IS WELL ESTABLISHED that the contractile response to a number of agonists including norepinephrine (NE) comprises two distinct components in Ca 2ϩ -containing medium: an initial phasic component that results from the inositol 1,4,5-trisphosphate [Ins(1,4,5)P 3 ]-mediated release of Ca 2ϩ from intracellular Ca 2ϩ stores followed by a tonic component that requires Ca 2ϩ entry in the continuous presence of the agonist,

Stimulated Tyrosine Phosphorylation of Phosphatidylinositol 3-Kinase Causes Acidic pH-Induced Contraction in Spontaneously Hypertensive Rat Aorta

“…Tyrosine phosphorylation has been shown to be associated with Ca 2ϩ entry through VDCC (Wijetunge et al, 1992(Wijetunge et al, , 1998Lagaud et al, 1999). A recent study has specifically shown the involvement …”

“…Consistently, tyrosine kinase inhibitors have been shown to attenuate vasoconstriction caused by a number of agents, including noradrenaline and angiotensin II in intact arteries (Di Salvo et al, 1993Laniyonu et al, 1994;Carmines et al, 2001). Recent studies have shown that the voltage-dependent Ca 2ϩ channels (VDCCs), activated by many vasoactive agents, are inhibited by tyrosine kinase inhibitors via tyrosine kinases (Wijetunge et al, 1992;Wijetunge et al, 1998;Lagaud et al, 1999). In addition to the effects on Ca 2ϩ channels, tyrosine kinases may regulate other mechanisms controlling the contractile state of smooth muscle cells.…”

The F-BAR Protein NOSTRIN Dictates the Localization of the Muscarinic M3 Receptor and Regulates Cardiovascular Function

“…High-resolution echocardiography analysis was performed using a Vevo2100-high resolution imaging system (VisualSonics, Toronto, Canada) with a 40-MHz transducer (MS-550D) as described. 34 Myograph vascular reactivity analysis of thoracic aortae and mesenteric arteries was performed on a DMT 610M small vessel myograph (Danish Myograph Technology, Aarhus, Denmark) as described 35,36 and analyzed using LabChart 7 software (AdInstruments, Oxford, United Kingdom). Hindlimb perfusion was measured as described.…”

Endothelium-independent vasodilation induced by kolaviron, a biflavonoid complex from Garcinia kola seeds, in rat superior mesenteric arteries

“…The concentration used for each blocker/inhibitor of K + channels is sufficient to antagonize selectively those channels in arterial smooth muscle (Nelson and Quayle, 1995;Lagaud et al, 1999;Cortes et al, 2001;Oliveira et al, 2006). After stabilization of the tonic contraction induced by PHE, increasing cumulative concentrations of KV (1, 10, 30, 100, 300, 500 and 1,000 µg/ml) were added to the organ bath.…”

“…To further investigate the mechanism of vasorelaxation induced by KV, concentrationresponse curves to CaCl2 were constructed using endothelium-denuded rings (Lagaud et al, 1999). Briefly, the rings were pre-contracted with 60 mM KCl to confirm tissue viability.…”