Nickel inhibits endothelin-induced contractions of vascular smooth muscle

1990 ◽  
Vol 258 (6) ◽  
pp. C1025-C1030 ◽  
Author(s):  
K. Blackburn ◽  
R. F. Highsmith
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Isometric Force ◽  
Inhibitory Effect ◽  
Rat Aorta ◽  
Porcine Coronary Artery ◽  
Force Development ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Dose Dependent

Endothelin (ET)-induced contractions of vascular smooth muscle (VSM) are dependent on extracellular Ca2+ yet display only partial sensitivity to L-type Ca2+ antagonists. The purpose of this study was to evaluate the effect of nickel (Ni2+), a Ca2+ channel antagonist with clearly documented differential potency toward L- vs. T-type Ca2+ currents on ET-mediated contractions in VSM. Treatment of rings of left anterior descending porcine coronary artery (LAD) with Ni2+ produced a profound dose-dependent inhibition of isometric force development in response to porcine ET (ET-1). At a concentration of 360 microM, Ni2+ exerted a significant inhibitory effect on contracture in response to doses of ET-1 ranging from 3 to 100 nM. In contrast, the same concentration of Ni2+ failed to significantly affect peak force development in response to KCl depolarization (5-77 mM) or to phenylephrine (0.3-30 mM). In addition, 360 microM Ni2+ significantly inhibited the contractile response of rat aorta to 10 nM ET-1. We conclude that ET-1 activates a Ni2(+)-sensitive process in VSM which may signal an additional Ca2+ influx pathway that appears to be functionally distinct from the L-type Ca2+ channel.

Sodium cromoglycate: evidence of tachykinin antagonist activity in the human skin

1993 ◽  
Vol 75 (1) ◽  
pp. 167-172 ◽  
Author(s):  
D. C. Crossman ◽  
M. R. Dashwood ◽  
G. W. Taylor ◽  
R. Wellings ◽  
R. W. Fuller
Keyword(s):  
Sodium Cromoglycate ◽  
Human Skin ◽  
High Performance ◽  
Gel Filtration ◽  
Inhibitory Effect ◽  
Intradermal Injection ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Dose Dependent

The mechanism of action of the antiasthmatic drug sodium cromoglycate (SCG) is unclear. One possibility is that SCG antagonizes the effects of the tachykinin substance P (SP), an agent known to cause airway edema. However, when SP is inhaled by humans, it has no demonstrable effect on airway function; therefore, the possibility that SCG prevents SP-induced changes in microvascular permeability was examined in human skin in vivo where potent edema-producing effects are seen. SCG (5–500 nmol) caused significant (P < 0.05) dose-dependent inhibition of SP-induced edema (wheal) formation when coadministered by intradermal injection. There was no effect on the nonreceptor-mediated flare response. SCG also significantly (P < 0.05) inhibited the wheal response to the related tachykinin neurokinin B but had no inhibitory effect on the cutaneous responses to histamine and prostaglandin E2. In addition, SCG (0.1–10 mM) caused dose-dependent inhibition of binding of SP labeled with 125I-labeled Bolton-Hunter to a number of tissues known to contain SP binding sites, as assessed by autoradiography. These concentrations were equivalent to the final concentrations of SCG found to inhibit the wheal response in the skin. The possibility that SCG interacted with SP was investigated both by gel filtration and high-performance liquid chromatography. No strong interaction was demonstrated with an 8,000 M excess of SCG under both hydrophobic and hydrophilic conditions. These results raise the possibility that SCG may have tachykinin antagonist properties.

scholarly journals The Vasorelaxant Effect ofp-Cymene in Rat Aorta Involves Potassium Channels

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Martapolyana T. M. Silva ◽  
Fernanda P. R. A. Ribeiro ◽  
Maria Alice M. B. Medeiros ◽  
Pedrita A. Sampaio ◽  
Yonara M. S. Silva ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Potassium Channels ◽  
Vascular Smooth Muscle ◽  
Channel Blocker ◽  
Antimicrobial Activities ◽  
Rat Aorta ◽  
Relaxant Effect ◽  
Vasorelaxant Effect ◽  
Dose Dependent ◽  
Relaxing Effect

The monoterpenes are the main constituents of most essential oils andp-cymene is a monoterpene commonly found in various species of aromatic herbs, which has been reported for anti-inflammatory, antinociceptive, and antimicrobial activities. However, there is no report concerning its pharmacological activity on the vascular smooth muscle. The aim of current work was to investigate the effects ofp-cymene in isolated rat aorta and also study its mechanism of action. In this work, we show thatp-cymene has a relaxant effect, in a dose-dependent way, on the vascular smooth muscle, regardless of the presence of the endothelium. Using a nonselective potassium channel blocker, the CsCl, the relaxant effect ofp-cymene was attenuated. In the presence of more selective potassium channels blockers, such as TEA or 4-AP, no change in the relaxant effect ofp-cymene was evidenced, indicating thatBKCaandKVchannels are not involved in that relaxant effect. However, in the presence of glibenclamide or BaCl2,KATPandKirblockers, respectively, the relaxant effect ofp-cymene was attenuated. The data presented indicate thatp-cymene has a relaxing effect on rat aorta, regardless of the endothelium, but with the participation of theKATPandKirchannels.

Blood pressure regulates the activity and function of the Na-K-2Cl cotransporter in vascular smooth muscle

2004 ◽  
Vol 286 (4) ◽  
pp. H1552-H1557 ◽  
Author(s):  
Gengru Jiang ◽  
Fatma Akar ◽  
Scott L. Cobbs ◽  
Koba Lomashvilli ◽  
Randala Lakkis ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Muscle Tone ◽  
Isometric Force ◽  
Blood Pressure Measurement ◽  
Acute Effect ◽  
Rat Aorta ◽  
Mean Blood Pressure ◽  
Acute Response

The Na-K-2Cl cotransporter (NKCC1) is one of several transporters that have been linked to hypertension, and its inhibition reduces vascular smooth muscle tone and blood pressure. NKCC1 in the rat aorta is stimulated by vasoconstrictors and inhibited by nitrovasodilators, and this is linked to the contractile state of the smooth muscle. To determine whether blood pressure also regulates NKCC1, we examined the acute effect of hypertension on NKCC1 in rats after aortic coarctation. In the hypertensive aorta (28-mmHg rise in mean blood pressure), an increase in NKCC1 activity (measured as bumetanide-sensitive 86Rb efflux) was apparent by 16 h and reached a plateau of 62% greater than control at 48 h. In contrast, there was a slight decrease in NKCC1 activity in the hypotensive aorta (21% decrease in mean blood pressure). Measurement of NKCC1 mRNA by real-time PCR revealed a fivefold increase in the hypertensive aorta compared with the hypotensive aorta or sham aorta. The inhibition by bumetanide of isometric force response to phenylephrine was significantly greater in the hypertensive aorta than in the control aorta or hypotensive aorta. We conclude that NKCC1 in rat aortic smooth muscle is regulated by blood pressure, most likely through changes in transporter abundance. This upregulation of NKCC1 is associated with a greater contribution to force generation in the hypertensive aorta. This is the first demonstration that NKCC1 in vascular smooth muscle is regulated by blood pressure and indicates that this transporter is important in the acute response of vascular smooth muscle to hypertension.

Contractile regulation of the Na+-K+-2Cl− cotransporter in vascular smooth muscle

2001 ◽  
Vol 281 (2) ◽  
pp. C579-C584 ◽  
Author(s):  
Fatma Akar ◽  
Gengru Jiang ◽  
Richard J. Paul ◽  
W. Charles O'Neill
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Isometric Force ◽  
Specific Inhibitor ◽  
Smooth Muscle Contraction ◽  
Rat Aorta ◽  
Direct Result ◽  
Aortic Smooth Muscle ◽  
Butanedione Monoxime ◽  
Stimulation Of

Vasoconstrictors activate the Na+-K+-2Cl− cotransporter NKCC1 in rat aortic smooth muscle, but the mechanism is unknown. Efflux of86Rb+ from rat aorta in response to phenylephrine (PE) was measured in the absence and presence of bumetanide, a specific inhibitor of NKCC1. Removal of extracellular Ca2+ completely abolished the activation of NKCC1 by PE. This was not due to inhibition of Ca2+-dependent K+ channels since blocking these channels with Ba2+ in Ca2+-replete solution did not prevent activation of NKCC1 by PE. Stimulation of NKCC1 by PE was inhibited 70% by 75 μM ML-9, 97% by 2 μM wortmannin, and 70% by 2 mM 2,3-butanedione monoxime, each of which inhibited isometric force generation in aortic rings. Bumetanide-insensitive Rb+efflux, an indication of Ca2+-dependent K+channel activity, was reduced by ML-9 but not by the other inhibitors. Stretching of aortic rings on tubing to increase lumen diameter to 120% of normal almost completely blocked the stimulation of NKCC1 by PE without inhibiting the stimulation by hypertonic shrinkage. We conclude that activation of the Na+-K+-2Cl− cotransporter by PE is the direct result of smooth muscle contraction through Ca2+-dependent activation of myosin light chain kinase. This indicates that the Na+-K+-2Cl− cotransporter is regulated by the contractile state of vascular smooth muscle.

Effects of length oscillation on the subsequent force development in swine tracheal smooth muscle

2000 ◽  
Vol 88 (6) ◽  
pp. 2246-2250 ◽  
Author(s):  
Lu Wang ◽  
Peter D. Paré ◽  
Chun Y. Seow
Keyword(s):  
Smooth Muscle ◽  
Isometric Force ◽  
Inhibitory Effect ◽  
Tidal Breathing ◽  
Temporary Reduction ◽  
Force Development ◽  
Rate Of Recovery ◽  
Length Changes ◽  
Force Reduction

It has been shown that deep inspiration (DI) taken before application of bronchoconstricting stimuli causes a reduction in the subsequent bronchoconstriction; a fast DI has a greater inhibitory effect than a slow DI. We hypothesize that periodic length changes imposed on a relaxed airway smooth muscle (ASM) would attenuate subsequent bronchoconstriction by disrupting the organization of the contractile apparatus, and this could be an important mechanism for the observed bronchoprotective effect of DI and tidal breathing. Length oscillations of different amplitude, frequency, and duration were applied to a relaxed muscle. The effects of such perturbations on force development were then assessed. Results show that oscillations reduce the subsequent force generation and that the magnitude of force reduction is proportional to amplitude and duration of the length oscillation. After the oscillation, isometric force recovered to the preoscillation level in a series of isometric contractions, and the rate of recovery was facilitated by frequent stimulation. The in vitro behavior of ASM found in this study could account for the observed temporary reduction in bronchoconstriction subsequent to a DI.

Antiplatelet Effect of Hsien-Ho-T'sao (Agrimonia Pilosa)

1985 ◽  
Vol 13 (01n04) ◽  
pp. 109-118 ◽  
Author(s):  
Jih-Pyang Wang ◽  
Mei-Feng Hsu ◽  
Che-Ming Teng
Keyword(s):  
Platelet Rich Plasma ◽  
Atp Release ◽  
Water Extract ◽  
Creatine Phosphate ◽  
Inhibitory Effect ◽  
Malondialdehyde Formation ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Induced Aggregation ◽  
Dose Dependent

The water extract of Hsien-Ho-T'sao (HHT) produced a dose-dependent inhibition on collagen-induced aggregation of platelet-rich plasma (PRP). The IC50 was about 3.5 mg/ml. In addition, HHT inhibited also the aggregation induced by ADP, A23187 or arachidonate in PRP. Greater inhibition was observed in the preparation of washed platelets. Increase of the calcium concentration in medium could not overcome the inhibitory effect of HHT. ATP release from platelets induced by collagen or A23187 was inhibited by HHT. In the presence of EDTA, ATP release caused by thrombin or A23187 was also inhibited by HHT. Malondialdehyde and thromboxane B2 formation was greatly inhibited by HHT in platelets challenged by collagen and thrombin. In arachidonate-stimulated platelets, thromboxane B2, but not malondialdehyde formation was inhibited. HHT showed more marked inhibition on aggregation in the presence of indomethacin, creatine phosphate/creatine phosphokinase or a combination of both. Hydrogen peroxide-induced hemolysis was makred reduced by HHT. It was concluded that HHT might have some membrane-active properties which interfered with the activation of phospholipase A2.

Dual Actions of Halothane on Intracellular Calcium Stores of Vascular Smooth Muscle

1996 ◽  
Vol 84 (3) ◽  
pp. 580-595 ◽  
Author(s):  
Takashi Akata ◽  
Walter A. Boyle
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Intracellular Calcium ◽  
Inhibitory Effect ◽  
Isometric Tension ◽  
Mesenteric Arteries ◽  
Calcium Stores ◽  
Free Solution ◽  
Dependent Inhibition ◽  
Permeabilized Muscle

Background Halothane has been reported to affect the integrity of intracellular Ca2+ stores in a number of tissues including vascular smooth muscle. However, the actions of halothane on intracellular Ca2+ stores are not yet fully understood. Methods Employing the isometric tension recording method, the action of halothane in isolated endothelium-denuded rat mesenteric arteries under either intact or beta-escinmembrane-permeabilized conditions was investigated. Results Halothane (0.125-5%) produced concentration-dependent contractions in Ca2+ free solution in both intact and membrane-permeabilized muscle strips. Ryanodine treatment or repetitive application of phenylephrine eliminated both caffeine-and halothane-induced contractions in the Ca2+ free solution. When either halothane and caffeine, caffeine and halothane, phenylephrine and halothane, or inositol 1,4,5-triphosphate and halothane were applied consecutively in the Ca2+ free solution in either intact or membrane-permeabilized muscle strips, the contraction induced by application of the second agent of the pair was inhibited compared to application of that agent alone. However, when procaine was applied before and during application of the first agent, the contraction induced by the first agent was inhibited and the contraction induced by the second agent was restored. Heparin inhibited the inositol 1,4,5-triphosphate-mediated contraction, but not contractions induced by halothane or caffeine. Halothane (0.125-5%), applied during Ca2+ loading, produced concentration-dependent inhibition of the caffeine contraction (used to estimate the amount of Ca2+ in the store) in both intact and membrane-permeabilized muscle strips. In contrast, halothane applied with procaine during Ca2+ loading produced concentration-dependent enhancement of the caffeine contraction. This enhancement was observed only in the intact but not in the membrane-permeabilized condition. Conclusions Halothane has two distinct actions on the intracellular Ca2+ stores of vascular smooth muscle, a Ca2+ releasing action and a stimulating action on Ca2+ uptake. Halothane releases Ca2+ from the stores that are sensitive to both caffeine/ryanodine and phenylephrine/inositol 1,4,5-triphosphate through a procaine-sensitive mechanism. The observed inhibitory effect on Ca2+ uptake is probably caused by the Ca2+ uptake after blockade of Ca2+ release may be membrane-mediated.

INHIBITORY EFFECT OP HALOTHANE AND ISOFLURANE ON CITOSOLIC Ca2+INCREASE AND CONTRACTION IN VASCULAR SMOOTH MUSCLE OF RAT AORTA

1991 ◽  
Vol 75 (3) ◽  
pp. A531-A531 ◽  
Author(s):  
H. TSUCHIDA ◽  
E. NOTSUKI ◽  
M. TAMAKAGE ◽  
S. FUJITA ◽  
A. NAMIKI
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Inhibitory Effect ◽  
Rat Aorta

Synthetic atrial peptide inhibits intracellular calcium release in smooth muscle

1986 ◽  
Vol 250 (1) ◽  
pp. C171-C174 ◽  
Author(s):  
K. D. Meisheri ◽  
C. J. Taylor ◽  
H. Saneii
Keyword(s):  
Smooth Muscle ◽  
Calcium Release ◽  
Rabbit Aorta ◽  
Inhibitory Effect ◽  
Physiological Salt Solution ◽  
Phasic Contraction ◽  
Dependent Inhibition ◽  
Isolated Rabbit Aorta ◽  
Dose Dependent Inhibition ◽  
45Ca Efflux

The effects of a synthetic atrial peptide (atriopeptin II; AP II) on the agonist-induced intracellular Ca2+ release was examined in the isolated rabbit aorta. The agonist-induced phasic contraction in a Ca2+-free physiological salt solution containing 2 mM ethyleneglycol-bis(beta-aminoethyl-ether)-N,N'-tetraacetic acid (EGTA-PSS) was used as an indicator of the intracellular Ca2+ release. The addition of AP II (10(-9)-10(-7) M) for 15 min to the tissue during the EGTA-PSS exposure caused a dose-dependent inhibition of norepinephrine (NE; 10(-6) M)-induced phasic contraction. The half-maximal inhibiting concentration of AP II was 3 X 10(-9) M, with 10(-7) M AP II causing 91% inhibition. This was confirmed by studying the inhibitory effect of AP II (10(-7) M) on NE-stimulated 45Ca efflux. Furthermore, the internal Ca2+ release by histamine (10(-5) M) and caffeine (25 mM), both of which share this internal Ca2+ pool with NE, was also inhibited by AP II. Thus AP II appears to be a potent inhibitor of the intracellular Ca2+ release that is utilized by various agonists for the activation of vascular smooth muscle. This may be an important mechanism by which AP II produces relaxation of blood vessels.

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