Interaction Between L-Type Ca2+ Channels and Sarcoplasmic Reticulum in the Regulation of Vascular Tone in Isolated Rat Small Arteries

The aim of our research is to study the effect relaxant action of diterpenoid alkaloids talatisamine, 14-O-benzoylthalatisamine and 14-O-acetylthalatisamine was studied using isolated rat aortic rings. Alkaloids significantly and dose-dependently inhibited contraction of the aortic rings caused by high KCl content. At the same time, under these conditions, alkaloids significantly reduced Ca2+-induced contraction of the aortic rings. The relaxing effects of alkaloids are significantly suppressed by verapamil, a potent potentiometer-dependent Ca2+ channel blocker. The alkaloids also significantly reduced norepinephrine-induced aortic ring contraction in normal as well as Ca2+ free Krebs solutions. The data obtained indicate that talatisamine, 14-benzoylthalatisamine and 14-O-acetylthalatisamine exhibit a pronounced relaxant effect in almost the same way in the case of contraction induced by a high content of KCl and norepinephrine. The mechanism of the relaxant action of alkaloids is probably complex and may include suppression of Ca2+influx through voltage-dependent and receptor-driven Ca2+ channels, as well as inhibition of Ca2+transport in the sarcoplasmic reticulum.

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Abstract 89: Enhanced TP Sensitivity and HO-dependent CO Release Mediates H2O2-Induced Vasoconstriction and Dilation: A Response Affected by Antioxidants

Hypertension ◽

10.1161/hyp.60.suppl_1.a89 ◽

2012 ◽

Vol 60 (suppl_1) ◽

Author(s):

Nitin Puri ◽

Fan Zhang ◽

Sumit Ranjan Monu ◽

Yilun Zhang ◽

Nader G Abraham ◽

...

Keyword(s):

Hydrogen Peroxide ◽

Vascular Tone ◽

Lipid Peroxides ◽

Internal Diameter ◽

Vascular Effects ◽

H2o2 Treatment ◽

Dilatory Response ◽

Regulation Of Vascular Tone ◽

Isolated Rat

Hydrogen peroxide (H2O2) is a non-radical oxidant and is employed to ascertain the role of redox mechanisms in regulation of vascular tone. Where both dilation and constriction have been reported in response to this oxidant; we examined the hypothesis that the ability of H2O2 to affect vasoconstriction or dilatation is conditioned by redox mechanisms and may be amenable to modulation by antioxidants. Freshly isolated rat renal interlobular (RIA) or mesenteric (MA) arteries were used for investigation of the effect of H2O2 on their internal diameter (ID), in the absence or presence of antioxidants including, tempol, PEG-SOD, BHT and biliverdin (BV). In arteries without antioxidant pretreatment, H2O2 (1.0 and 10.0 μM) reduced (p< 0.05) the ID of RIA (90.0±0.6 to 85.0±1.9 and 71.6±1.4 μm, respectively) and MA (90.4±2.3 to 85.0±2.1 and 74.2±1.8 μm, respectively); a response obliterated by all antioxidants used (p<0.05). However, in contrast to tempol and PEG-SOD, antioxidants targeting lipid peroxides and OH. (BHT, BV) not only blocked constriction but also uncovered vasodilation in response to H2O2 (91.3±2.5 to 95.2±2.4 and 102.5±2.8 μm, with BHT), which was also endothelium dependent [Δ ID- BHT+H2O2 (10 μM): 11.85±0.73 vs. in endothelium denuded: 0.80±0.49 μm, p<0.05]. Without enhancing vascular TxB2 synthesis (2.01±0.72 vs. 1.87±0.41 ng/mg/hr) H2O2 caused vasoconstriction which was blocked (p<0.05) by inhibitors of the COX-TXA2 pathway (indomethacin, SQ29548). However, H2O2 treatment sensitized the arteries to a TP agonist- U46619 (EC50: 0.63±0.07 vs. 0.17±0.08 nmol/l, in arteries without and with H2O2, respectively), an effect reversed by PEG-SOD pretreatment. The dilatory response to H2O2 was accompanied by enhanced vascular heme oxygenase (HO)-dependent CO generation (BHT: 157.2±19.9 vs. BHT+H2O2: 301.25±25.3, p<0.05 and BV: 162.6±17.3 vs. BV + H2O2: 255.9±19.9, p<0.05 as opposed to tempol: 135.0±19.9 vs. tempol + H2O2: 125.3±18.6 pmol/mg/hr) and was abolished (p<0.05) by either an inhibitor of HO or in RIA from animals treated with HO-1& 2 AS-ODN. These results demonstrate that H2O2 has antioxidant-modifiable pleotropic vascular effects brought about by enhanced TP sensitivity to constrictor agonist(s) or dilatory HO-derived products.

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Roles of different peptide fragments derived from proadrenomedullin in the regulation of vascular tone in isolated rat aorta

Peptides ◽

10.1016/s0196-9781(03)00109-8 ◽

2003 ◽

Vol 24 (4) ◽

pp. 563-568 ◽

Cited By ~ 7

Author(s):

Juxiang Li ◽

Yongsheng Ren ◽

Xianhong Dong ◽

Guangzhen Zhong ◽

Shengying Wu ◽

...

Keyword(s):

Vascular Tone ◽

Rat Aorta ◽

Peptide Fragments ◽

Regulation Of Vascular Tone ◽

Isolated Rat

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Regulation of vascular tone by UTP and UDP in isolated rat intrapulmonary arteries

European Journal of Pharmacology ◽

10.1016/s0014-2999(99)00150-8 ◽

1999 ◽

Vol 370 (2) ◽

pp. 139-143 ◽

Cited By ~ 26

Author(s):

Annalisa Rubino ◽

Laila Ziabary ◽

Geoffrey Burnstock

Keyword(s):

Vascular Tone ◽

Regulation Of Vascular Tone ◽

Isolated Rat

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Heterogeneity of L-type calcium current density in coronary smooth muscle

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1997.273.4.h2083 ◽

1997 ◽

Vol 273 (4) ◽

pp. H2083-H2089 ◽

Cited By ~ 15

Author(s):

D. K. Bowles ◽

Q. Hu ◽

M. H. Laughlin ◽

M. Sturek

Keyword(s):

Smooth Muscle ◽

Current Density ◽

Vascular Tone ◽

Coronary Circulation ◽

Arterial Diameter ◽

Miniature Swine ◽

Heterogeneous Distribution ◽

Small Arteries ◽

Voltage Gated ◽

Regulation Of Vascular Tone

Heterogeneity of vascular responses to physiological and pharmacological stimuli has been demonstrated throughout the coronary circulation. Typically, this heterogeneity is based on vessel size. Although the cellular mechanisms for this heterogeneity are unknown, one plausible factor may be heterogeneous distribution of ion channels important in regulation of vascular tone. Because of the importance of voltage-gated Ca2+ channels in regulation of vascular tone, we hypothesized that these channels would be unequally distributed throughout the coronary arterial bed. To test this hypothesis, voltage-gated Ca2+current was measured in smooth muscle from conduit arteries (>1.0 mm), small arteries (200–250 μm), and large arterioles (75–125 μm) of miniature swine using whole cell voltage-clamp techniques. With 2 mM Ca2+ or 10 mM Ba2+ as charge carrier, voltage-gated Ca2+ current density was inversely related to arterial diameter, i.e., large arterioles > small arteries > conduit. Peak inward currents (10 mM Ba2+) were increased ∼2.5- and ∼1.5-fold in large arterioles and small arteries, respectively, compared with conduit arteries (−5.58 ± 0.53, −3.54 ± 0.34, and −2.26 ± 0.31 pA/pF, respectively). In physiological Ca2+ (2 mM), small arteries demonstrated increased inward current at membrane potentials within the physiological range for vascular smooth muscle (as negative as −40 mV) compared with conduit arteries. In addition, cells from large arterioles showed a negative shift in the membrane potential for half-maximal activation compared with small and conduit arteries (−13.23 ± 0.88, −6.22 ± 1.35, and −8.62 ± 0.81 mV, respectively; P < 0.05). Voltage characteristics and dihydropyridine sensitivity identified this Ca2+ current as predominantly L-type current in all arterial sizes. We conclude that L-type Ca2+ current density is inversely related to arterial diameter within the coronary arterial vasculature. This heterogeneity of Ca2+ current density may provide, in part, the basis for functional heterogeneity within the coronary circulation.

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Na+-Ca2+ exchange contributes to increase of cytosolic Ca2+ concentration during depolarization in heart muscle

AJP Cell Physiology ◽

10.1152/ajpcell.1986.250.4.c651 ◽

1986 ◽

Vol 250 (4) ◽

pp. C651-C656 ◽

Cited By ~ 43

Author(s):

S. S. Sheu ◽

V. K. Sharma ◽

A. Uglesity

Keyword(s):

Sarcoplasmic Reticulum ◽

Channel Blocker ◽

Ventricular Myocytes ◽

Transport Systems ◽

High K ◽

K Concentration ◽

Cardiac Excitation ◽

Ca2 Channels ◽

Isolated Rat

The possible role of Na+-Ca2+ exchange in contributing to depolarization-induced increase in cytosolic Ca2+ concentration ([Ca2+]i) of isolated rat ventricular myocytes was investigated. Measured with the Ca2+-sensitive indicator quin 2, [Ca2+]i increased from 177 +/- 12 (mean +/- SE, n = 11) to 468 +/- 41 nM when cells were depolarized with solutions containing 50 mM KCl [high extracellular K+ concentration ([K+]o)]. Approximately 73% of this high-[K+]o-induced increase in [Ca2+]i was abolished by the Ca2+ channel blocker verapamil (5 microM). For cells pretreated with 10 mM caffeine to deplete the Ca2+ stored in sarcoplasmic reticulum, 50 mM KCl still produced an increase in [Ca2+]i, even in the presence of 5 microM verapamil. However, if extracellular Na+ was replaced by Li+ or tris(hydroxymethyl)aminomethane, this increase was completely abolished. The results suggest that, in addition to voltage-sensitive Ca2+ channels, voltage-sensitive Na+-Ca2+ exchange can also contribute to the increase in [Ca2+]i on depolarization. Therefore both Ca2+ transport systems may play important roles in regulating cardiac excitation and contraction.

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Characteristic of the vasorlaxant action of the talatisamine alkaloid and its derivatives

Pharmaceutics and Pharmacology Research ◽

10.31579/2693-7247/027 ◽

2021 ◽

Vol 4 (2) ◽

pp. 01-05

Author(s):

Mirzayeva Yu.T

Keyword(s):

Sarcoplasmic Reticulum ◽

Channel Blocker ◽

Aortic Ring ◽

Diterpenoid Alkaloids ◽

Relaxant Effect ◽

Ring Contraction ◽

Voltage Dependent ◽

Ca2 Channels ◽

Isolated Rat

The aim of our research is to study the effect relaxant action of diterpenoid alkaloids talatisamine, 14-O-benzoylthalatisamine and 14-O-acetylthalatisamine was studied using isolated rat aortic rings. Alkaloids significantly and dose-dependently inhibited contraction of the aortic rings caused by high KCl content. At the same time, under these conditions, alkaloids significantly reduced Ca2+-induced contraction of the aortic rings. The relaxing effects of alkaloids are significantly suppressed by verapamil, a potent potentiometer-dependent Ca2+ channel blocker. The alkaloids also significantly reduced norepinephrine-induced aortic ring contraction in normal as well as Ca2+ free Krebs solutions. The data obtained indicate that talatisamine, 14-benzoylthalatisamine and 14-O-acetylthalatisamine exhibit a pronounced relaxant effect in almost the same way in the case of contraction induced by a high content of KCl and norepinephrine. The mechanism of the relaxant action of alkaloids is probably complex and may include suppression of Ca2+influx through voltage-dependent and receptor-driven Ca2+ channels, as well as inhibition of Ca2+transport in the sarcoplasmic reticulum.

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Role of Cav1.2 L-type Ca2+ channels in vascular tone: effects of nifedipine and Mg2+

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.01214.2005 ◽

2007 ◽

Vol 292 (1) ◽

pp. H415-H425 ◽

Cited By ~ 47

Author(s):

Jin Zhang ◽

Roberto Berra-Romani ◽

Martina J. Sinnegger-Brauns ◽

Jõrg Striessnig ◽

Mordecai P. Blaustein ◽

...

Keyword(s):

Vascular Tone ◽

Myogenic Tone ◽

Wild Type ◽

Small Arteries ◽

New Information ◽

High K ◽

Key Factor ◽

Ca2 Channels ◽

External K

Ca2+ entry via L-type voltage-gated Ca2+ channels (LVGCs) is a key factor in generating myogenic tone (MT), as dihydropyridines (DHPs) and other LVGC blockers, including Mg2+, markedly reduce MT. Recent reports suggest, however, that elevated external Mg2+ concentration and DHPs may also inhibit other Ca2+-entry pathways. Here, we explore the contribution of LVGCs to MT in intact, pressurized mesenteric small arteries using mutant mice (DHPR/R) expressing functional but DHP-insensitive Cav1.2 channels. In wild-type (WT), but not DHPR/R, mouse arteries, nifedipine (0.3–1.0 μM) markedly reduced MT and vasoconstriction induced by high external K+ concentrations ([K+]o), a measure of LVGC-mediated Ca2+ entry. Blocking MT and high [K+]o-induced vasoconstriction by <1 μM nifedipine in WT but not in DHPR/R arteries implies that Ca2+ entry via Cav1.2 LVGCs is obligatory for MT and that nifedipine inhibits MT exclusively by blocking LVGCs. We also examined the effects of Mg2+ on MT and LVGCs. High external Mg2+ concentration (10 mM) blocked MT, slowed the high [K+]o-induced vasoconstrictions, and decreased their amplitude in WT and DHPR/R arteries. To verify that these effects of Mg2+ are due to block of LVGCs, we characterized the effects of extracellular and intracellular Mg2+ on LVGC currents in isolated mesenteric artery myocytes. DHP-sensitive LVGC currents are inhibited by both external and internal Mg2+. The results indicate that Mg2+ relaxes MT by inhibiting Ca2+ influx through LVGCs. These data provide new information about the central role of Cav1.2 LVGCs in generating and maintaining MT in mouse mesenteric small arteries.

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