Evidence against the role of α1-adrenoceptor reserve in buffering the inhibitory effect of nifedipine on the contractility of canine vascular smooth muscle

The relationship between the postsynaptic α1-adrenoceptor reserve and the sensitivity of vasoconstriction induced by α-adrenoceptor agonists to the dihydropyridine Ca2+ entry blocker nifedipine was investigated in isolated muscle strips of dog mesenteric artery (DMA) and saphenous vein (DSV). The amplitudes of the contractile responses of DMA induced by phenylephrine were the same as those in DSV in the presence and in the absence of extracellular Ca2+. The use of 3 × 10−9 M phenoxybenzamine to irreversibly block the α1-adrenoceptors revealed a marked difference in the size of the α1-adrenoceptor reserve between DMA (40%) and DSV (7%). In spite of a larger receptor reserve, the contractile responses induced by phenylephrine in DMA were more sensitive to nifedipine compared with those in DSV. These results suggest that the postsynaptic α1-adrenoceptor reserve in vascular smooth muscle, at least in DMA and DSV, does not play an important role in buffering the inhibitory effect of nifedipine on the contractile response to a full agonist of α1-adrenoceptors. Other factors, such as the difference in the membrane depolarizing effect, the ability to utilize intracellular Ca2+ for contraction, and the possible existence of α1-adrenoceptor subtypes, may contribute to the different inhibitory effects of nifedipine on these blood vessels.Key words: adrenoceptors, nifedipine, smooth muscle, calcium, saphenous vein, mesenteric artery.

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Inhibitory effects of tetramethyl and tetraethyl derivatives of pyrazine on dog saphenous vein

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y91-173 ◽

1991 ◽

Vol 69 (8) ◽

pp. 1184-1189 ◽

Cited By ~ 9

Author(s):

Z. L. Wang ◽

C. Y. Kwan ◽

A. Ohta ◽

M. C. Chen

Keyword(s):

Smooth Muscle ◽

Saphenous Vein ◽

Inhibitory Effect ◽

Induced Responses ◽

Adrenergic Agonist ◽

Dog Saphenous Vein ◽

Contractile Responses ◽

Intracellular Ca ◽

Prostaglandin F ◽

Muscle Calcium

The effects of two structurally similar pyrazine derivatives, tetramethylpyrazine (TMP) and tetraethylpyrazine (TEP) on the contractile responses of dog saphenous vein to KCl (via membrane depolarization), phenylephrine (PHE, α1-adrenergic agonist), and B-HT 920 (α2-adrenergic agonist) were investigated. The relaxant or inhibitory effect of TMP and TEP was most potent on KCl-induced responses and least potent on PHE-induced responses. Their effect on KCl-induced responses was more prominent at 30 mM KCl than at 100 mM KCl. In Ca2+-free medium, PHE and B-HT 920 elicited transient responses, which were also markedly and reversibly inhibited by TMP and TEP. Similar results were also obtained when prostaglandin F2α was used as an agonist. In all four types of contractile responses involving different receptors, the inhibitory effect of TEP was consistently more potent than that of TMP. We conclude that both TMP and TEP behave as a nonselective smooth muscle relaxant having similar and multiple actions including their general interference with the processes involving both Ca2+ entry and intracellular Ca2+ release.Key words: vascular smooth muscle, calcium channels, tetramethylpyrazine, tetraethylpyrazine, α-adrenoceptors, saphenous vein.

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Chloride-dependent calcium transients induced by angiotensin II in vascular smooth muscle cells

AJP Cell Physiology ◽

10.1152/ajpcell.00605.2002 ◽

2004 ◽

Vol 286 (1) ◽

pp. C112-C118 ◽

Cited By ~ 7

Author(s):

Yunn-Hwa Ma ◽

Hsiao-Wen Wei ◽

Kwan-Hwa Su ◽

Harlan E. Ives ◽

R. Curtis Morris

Keyword(s):

Smooth Muscle ◽

Angiotensin Ii ◽

Vascular Smooth Muscle ◽

Smooth Muscle Cells ◽

Vascular Smooth Muscle Cells ◽

Muscle Cells ◽

Ang Ii ◽

Intracellular Ca ◽

The Difference ◽

Peak Increase

Cl– is essential for the vasoconstrictive response to angiotensin II (ANG II). In vascular smooth muscle cells (VSMC), we determined whether ANG II-induced transient increase in intracellular Ca2+ concentration ([Ca2+]i) is Cl– dependent. After incubating the cells at different extracellular Cl– concentration ([Cl–]e) for 40 min, the ANG II-induced Ca2+ transients at 120 meq/l Cl– were more than twice those at either 80 or 20 meq/l Cl–. Replacing Cl– with bicarbonate or gluconate yielded similar results. In addition, after removal of extracellular Ca2+, ANG II-induced as well as platelet-derived growth factor-induced Ca2+ release exhibited Cl– dependency. The difference of Ca2+ release with high vs. low [Cl–]e was not affected by acutely altering [Cl–]e 1 min before administration of ANG II when [Cl–]i was yet to be equilibrated with [Cl–]e. Pretreatment of a Cl– channel inhibitor, 5-nitro-2-(3-phenylpropylamino)benzoic acid, increased ANG II-induced Ca2+ release and entry at 20 meq/l Cl– but did not alter those at 120 meq/l Cl–. However, after equilibration, a reduced [Cl–]e did not affect thapsigargin-induced Ca2+ release, suggesting that Cl– may not affect the size of intracellular Ca2+ stores. Nevertheless, at high [Cl–], the peak increase of inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] induced by ANG II was approximately sixfold that at low [Cl–]. Thus the Cl–-dependent effects of ANG II on Ca2+ transients may be mediated, at least in part, by a Cl–-dependent Ins(1,4,5)P3 accumulation in VSMC.

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The effects of EGTA on vascular smooth muscle contractility in calcium-free medium

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y88-172 ◽

1988 ◽

Vol 66 (8) ◽

pp. 1053-1056 ◽

Cited By ~ 32

Author(s):

Y. Y. Guan ◽

C. Y. Kwan ◽

E. E. Daniel

Keyword(s):

Smooth Muscle ◽

Vascular Smooth Muscle ◽

Physiological Saline ◽

Mesenteric Arteries ◽

Induced Response ◽

Free Medium ◽

Smooth Muscle Contractility ◽

Contractile Responses ◽

Low Concentrations ◽

Intracellular Ca

The effect of EGTA, commonly present in Ca2+-free physiological saline solution, on the contractile responses induced by Ca2+ and phenylephrine was studied in dog mesenteric arteries and aortas of rats and rabbits. EGTA substantially enhanced the contractile responses of these vascular strips or rings to added Ca2+ after a prolonged preincubation period in the Ca2+-free medium. The maximal level of the enhanced contractile responses was independent of EGTA concentration, but the rate of the maximal responses was faster at higher EGTA concentration, presumably as a result of faster removal of intracellular Ca2+. Such a Ca2+-induced response was sensitive to the Ca2+ antagonist, nifedipine. EGTA present at low concentrations (50 and 400 μM) in Ca2+-free medium also inhibited the phenylephrine-induced contractile response more prominently for the longer preincubation periods of the vascular tissues in Ca2+-free medium. Our results suggest that EGTA, even when added at low concentrations to the vascular smooth muscle for a sufficiently long period in a Ca2+-free medium, may cause destabilization of the cell membranes leading to increased permeability to subsequently added Ca2+. EGTA may also remove the superficially bound Ca2+ and subsequently reduce the intracellular Ca2+ pool via extraction of the intracellular Ca2+ at the cell membrane surfaces.

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Effects of salbutamol on intracellular calcium oscillations in porcine airway smooth muscle

Journal of Applied Physiology ◽

10.1152/jappl.1997.82.6.1836 ◽

1997 ◽

Vol 82 (6) ◽

pp. 1836-1843 ◽

Cited By ~ 16

Author(s):

Y. S. Prakash ◽

H. F. M. Van Der Heijden ◽

M. S. Kannan ◽

G. C. Sieck

Keyword(s):

Smooth Muscle ◽

Intracellular Calcium ◽

Airway Smooth Muscle ◽

Inhibitory Effect ◽

Calcium Oscillations ◽

Adrenoceptor Agonist ◽

Intracellular Ca ◽

Adrenoceptor Agonists ◽

A Cell ◽

Agonist Concentration

Prakash, Y. S., H. F. M. van der Heijden, M. S. Kannan, and G. C. Sieck. Effects of salbutamol on intracellular calcium oscillations in porcine airway smooth muscle. J. Appl. Physiol. 82(6): 1836–1843, 1997.—Relaxation of airway smooth muscle (ASM) by β-adrenoceptor agonists involves reduction of intracellular Ca2+concentration ([Ca2+]i). In porcine ASM cells, acetylcholine induces [Ca2+]ioscillations that display frequency modulation by agonist concentration and basal [Ca2+]i. We used real-time confocal microscopy to examine the effect of salbutamol (1 nM to 1 μM), a β2-adrenoceptor agonist, on [Ca2+]ioscillations in freshly dissociated porcine ASM cells. Salbutamol decreased the frequency of [Ca2+]ioscillations in a concentration-dependent fashion, completely inhibiting the oscillations at 1 μM. These effects were mimicked by a cell-permeant analog of adenosine 3′,5′-cyclic monophosphate. The inhibitory effect of salbutamol was partially reversed by BAY K 8644. Salbutamol reduced [Ca2+]ieven when sarcoplasmic reticulum (SR) Ca2+ reuptake and Ca2+ influx were blocked. Lanthanum blockade of Ca2+ efflux attenuated the inhibitory effect of salbutamol on [Ca2+]i. The [Ca2+]iresponse to caffeine was unaffected by salbutamol. On the basis of these results, we conclude that β2-adrenoceptor agonists have little effect on SR Ca2+ release in ASM cells but reduce [Ca2+]iby inhibiting Ca2+ influx through voltage-gated channels and by enhancing Ca2+ efflux.

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Contractile and Endothelium-Dependent Dilatory Responses of Cerebral Arteries at Various Extracellular Magnesium Concentrations

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.1991.20 ◽

1991 ◽

Vol 11 (1) ◽

pp. 161-164 ◽

Cited By ~ 21

Author(s):

Mária Faragó ◽

Csaba Szabó ◽

Eörs Dóra ◽

Ildikó Horváth ◽

Arisztid G. B. Kovách

Keyword(s):

Smooth Muscle ◽

Vascular Reactivity ◽

Calcium Influx ◽

Cerebral Arteries ◽

Inhibitory Effect ◽

Contractile Responses ◽

Middle Cerebral Arteries ◽

The Right ◽

Endothelial Receptor

To clarify the effect of extracellular magnesium (Mg2+) on the vascular reactivity of feline isolated middle cerebral arteries, the effects of slight alterations in the Mg2+ concentration on the contractile and endothelium-dependent dilatory responses were investigated in vitro. The contractions, induced by 10−8-10−5 M norepinephrine, were significantly potentiated at low Mg2+ (0.8 m M v. the normal, 1.2 m M). High (1.6 and 2.0 m M) Mg2+ exhibited an inhibitory effect on the contractile responses. No significant changes, however, in the EC50 values for norepinephrine were found. The endothelium-dependent relaxations induced by 108–10−5 M acetylcholine were inhibited by high (1.6 and 2.0 m M) Mg2+. Lowering of the Mg2+ concentration to 0.8 m M or total withdrawal of this ion from the medium failed to alter the dilatory potency of acetylcholine. The changes in the dilatory responses also shifted the EC50 values for acetylcholine to the right. The present results show that the contractile responses of the cerebral arteries are extremely susceptible to the changes of Mg2+ concentrations. In response to contractile and endothelium-dependent dilatory agonists, Mg2+ probably affects both the calcium influx into the endothelial and smooth muscle cells as well as the binding of acetylcholine to its endothelial receptor. Since Mg2+ deficiency might facilitate the contractile but not the endothelium-dependent relaxant responses, the present study supports a role for Mg2+ deficiency in the development of the cerebral vasospasm.

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Growth-dependent alterations of intracellular Ca(2+)-handling mechanisms of vascular smooth muscle cells. PDGF negatively regulates functional expression of voltage-dependent, IP3-mediated, and CA(2+)-induced Ca2+ release channels.

Circulation Research ◽

10.1161/01.res.69.5.1327 ◽

1991 ◽

Vol 69 (5) ◽

pp. 1327-1339 ◽

Cited By ~ 24

Author(s):

M Masuo ◽

T Toyo-oka ◽

W S Shin ◽

T Sugimoto

Keyword(s):

Smooth Muscle ◽

Vascular Smooth Muscle ◽

Smooth Muscle Cells ◽

Vascular Smooth Muscle Cells ◽

Muscle Cells ◽

Functional Expression ◽

Voltage Dependent ◽

Intracellular Ca

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Ets-1 is an early response gene activated by ET-1 and PDGF-BB in vascular smooth muscle cells

AJP Cell Physiology ◽

10.1152/ajpcell.1998.274.2.c472 ◽

1998 ◽

Vol 274 (2) ◽

pp. C472-C480 ◽

Cited By ~ 83

Author(s):

Shinji Naito ◽

Shunichi Shimizu ◽

Shigeto Maeda ◽

Jianwei Wang ◽

Richard Paul ◽

...

Keyword(s):

Gene Expression ◽

Smooth Muscle ◽

Vascular Smooth Muscle ◽

Smooth Muscle Cells ◽

Vascular Smooth Muscle Cells ◽

Inositol Phosphate ◽

Muscle Cells ◽

Tetraacetic Acid ◽

Acetoxymethyl Ester ◽

Intracellular Ca

Ets-1 is a transcription factor that activates expression of matrix-degrading proteinases such as collagenase and stromelysin. To study the control of ets-1 gene expression in rat vascular smooth muscle cells (VSMC), cells were exposed to factors known to regulate VSMC migration and proliferation. Platelet-derived growth factor-BB (PDGF-BB), endothelin-1 (ET-1), and phorbol 12-myristate 13-acetate (PMA) induced a dose-dependent expression of ets-1 mRNA. These effects were abrogated by inhibition of protein kinase C (PKC) by H-7 or chronic PMA treatment. Ets-1 mRNA was superinduced by PDGF-BB and ET-1 in the presence of cycloheximide. The chelation of intracellular Ca2+ by 1,2-bis(2-aminophenoxy)ethane- N, N, N′, N′-tetraacetic acid-acetoxymethyl ester and the depletion of endoplasmic reticulum intracellular Ca2+concentration ([Ca2+]i) by thapsigargin inhibited PDGF-BB- and ET-1-induced ets-1 mRNA, whereas ethylene glycol-bis(β-aminoethyl ether)- N, N, N′, N′-tetraacetic acid had no effect. However, [Ca2+]irelease alone was not sufficient to increase ets-1 mRNA. Forskolin blocked ET-1-, PDGF-BB-, and PMA-induced ets-1 mRNA, as well as inositol phosphate formation, consistent with an effect through impairment of PKC activation. Inhibitors of ets-1 gene expression, such as H-7 and herbimycin A, inhibited the ET-1 induction of collagenase I mRNA. We propose that ets-1 may be an important element in the orchestration of matrix proteinase expression and of vascular remodeling after arterial injury.

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