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

1991 ◽  
Vol 69 (8) ◽  
pp. 1184-1189 ◽  
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.

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

1990 ◽  
Vol 68 (10) ◽  
pp. 1346-1350 ◽  
Author(s):  
Yong-Yuan Guan ◽  
Chiu-Yin Kwan ◽  
Edwin E. Daniel
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Saphenous Vein ◽  
Mesenteric Artery ◽  
Inhibitory Effect ◽  
Contractile Responses ◽  
Intracellular Ca ◽  
Adrenoceptor Agonists ◽  
The Difference ◽  
Muscle Calcium

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.

Does in vitro activation of postsynaptic α2-adrenoceptor utilize intracellular Ca2+ for contraction in dog saphenous vein?

1989 ◽  
Vol 67 (9) ◽  
pp. 1086-1091 ◽  
Author(s):  
Y. Y. Guan ◽  
C. Y. Kwan ◽  
E. E. Daniel
Keyword(s):  
Saphenous Vein ◽  
Krebs Solution ◽  
Free Medium ◽  
High Concentration ◽  
Dog Saphenous Vein ◽  
Ph Buffering ◽  
Intracellular Ca ◽  
Muscle Calcium ◽  
Subsequent Addition

Dog saphenous vein spiral strips were employed to determine whether an intracellular source of Ca2+ is used for contraction upon activation of the α2-adrenoceptor by B-HT 920 in Ca2+-free Krebs solution containing 50 μM EGTA. The studies were carried out in parallel with the activation of the α1-adrenoceptor by phenylephrine (Phe) under the condition that B-HT 920 (10−5 M) and Phe (2 × 10−6 M) gave rise to a similar level of responses in Ca2+-containing Krebs solution. A similar level of responses to these agonists at equieffective concentrations in Ca2+-free medium were also observed. Such responses to Phe and B-HT 920 were inhibited by 10−7 M rauwolscine and 10−7 M prazosin, respectively, and were not affected by 10−7 M nifedipine or 5 mM Mn2+. The responses to B-HT 920 (10−5 M) and submaximal concentration of Phe (2 × 10−6 M) in Ca2+-free medium were additive. However, if the vascular strips were first contracted maximally with 10−4 M Phe in Ca+2-free medium to deplete the intracellular Ca store, subsequent addition of B-HT 920 failed to induce additional response. Our results strongly suggest that activation of α2-adrenoceptor in dog saphenous vein in Ca2+-free medium indeed utilizes intracellular Ca2+ for contraction. We also found that the failure of earlier studies to demonstrate the contractile effects of B-HT 920 in dog saphenous vein was due to experimental artifacts derived from the use of high concentration of EGTA and artificial pH-buffering reagent.Key words: adrenoceptor, saphenous vein, vascular muscle, calcium.

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

1991 ◽  
Vol 11 (1) ◽  
pp. 161-164 ◽  
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.

Gender-dependent modulation of α1-adrenergic responses in rat mesenteric arteries

2003 ◽  
Vol 284 (5) ◽  
pp. H1737-H1743 ◽  
Author(s):  
Alyson P. McKee ◽  
Dee A. Van Riper ◽  
Cathy A. Davison ◽  
Harold A. Singer
Keyword(s):  
Smooth Muscle ◽  
Endothelial Damage ◽  
Selective Inhibitor ◽  
Mesenteric Arteries ◽  
Resistance Arteries ◽  
Adrenergic Agonist ◽  
Contractile Responses ◽  
Cyclooxygenase 1 ◽  
Acid Metabolites ◽  
Selective Increase

The purpose of this study was to test the hypothesis that pathways modulating vasoconstriction in rat mesenteric resistance arteries are gender dependent. Net contractile responses to phenylephrine were significantly increased by endothelium disruption in arteries from males but not females. This gender-dependent effect was stimulus specific, because disruption of endothelium increased reactivity to serotonin comparably in arteries from both genders. Ovariectomy unmasked an increase in net α1-adrenergic contractile responsiveness after endothelium disruption, suggesting α1-adrenergic-stimulated production of endothelial vasodilators is suppressed in control females by gonadal sex steroids. Production of modulatory endothelium-derived vasodilators in males is balanced by production of vasoconstricting arachidonic acid metabolites. This was revealed by decreased α1-adrenergic contractile responses in arteries from males after pretreatment with indomethacin or the cyclooxygenase-1 selective inhibitor SC-560. The indomethacin-induced effect persisted after endothelium disruption, indicating smooth muscle as the source of cyclooxygenase-1-derived vasoconstrictors and was attenuated after orchiectomy. This study indicates gender differences in the expression of two pathways modulating α1-adrenergic sensitivity in mesenteric arteries: an endothelium-dependent vasodilator pathway and a balancing smooth muscle cyclooxygenase-1-dependent vasoconstrictor pathway. One consequence of these differences is that endothelial damage produces a selective increase in α1-adrenergic agonist reactivity in arteries from males.

The Relationship of Human Saphenous Vein Smooth Muscle Contractile Responses to Donor Age and Gender

1995 ◽  
Vol 29 (1) ◽  
pp. 15-21 ◽  
Author(s):  
Kelvin G. M. Brockbank ◽  
Mark G. Davies ◽  
Shirley M. Fields ◽  
Per-Otto Hagen
Keyword(s):  
Smooth Muscle ◽  
Saphenous Vein ◽  
Donor Age ◽  
Human Saphenous Vein ◽  
Age And Gender ◽  
Contractile Responses ◽  
And Gender ◽  
Relationship Of ◽  
The Relationship ◽  
Muscle Contractile

L-type Ca2+ channels, resting [Ca2+]i, and ET-1-induced responses in chronically hypoxic pulmonary myocytes

2000 ◽  
Vol 279 (5) ◽  
pp. L884-L894 ◽  
Author(s):  
Larissa A. Shimoda ◽  
James S. K. Sham ◽  
Tenille H. Shimoda ◽  
J. T. Sylvester
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Chronic Hypoxia ◽  
Induced Responses ◽  
Arterial Smooth Muscle Cell ◽  
Slight Effect ◽  
Intracellular Ca ◽  
Pulmonary Arterial ◽  
Pulmonary Arterial Smooth Muscle ◽  
Ca2 Channels

In the lung, chronic hypoxia (CH) causes pulmonary arterial smooth muscle cell (PASMC) depolarization, elevated endothelin-1 (ET-1), and vasoconstriction. We determined whether, during CH, depolarization-driven activation of L-type Ca2+ channels contributes to 1) maintenance of resting intracellular Ca2+ concentration ([Ca2+]i), 2) increased [Ca2+]i in response to ET-1 (10−8 M), and 3) ET-1-induced contraction. Using indo 1 microfluorescence, we determined that resting [Ca2+]i in PASMCs from intrapulmonary arteries of rats exposed to 10% O2 for 21 days was 293.9 ± 25.2 nM (vs. 153.6 ± 28.7 nM in normoxia). Resting [Ca2+]i was decreased after extracellular Ca2+ removal but not with nifedipine (10−6 M), an L-type Ca2+ channel antagonist. After CH, the ET-1-induced increase in [Ca2+]i was reduced and was abolished after extracellular Ca2+ removal or nifedipine. Removal of extracellular Ca2+ reduced ET-1-induced tension; however, nifedipine had only a slight effect. These data indicate that maintenance of resting [Ca2+]i in PASMCs from chronically hypoxic rats does not require activation of L-type Ca2+ channels and suggest that ET-1-induced contraction occurs by a mechanism primarily independent of changes in [Ca2+]i.

Role of G proteins in agonist-induced Ca2+ sensitization of tracheal smooth muscle

1998 ◽  
Vol 275 (4) ◽  
pp. L748-L755 ◽  
Author(s):  
Thomas L. Croxton ◽  
Boris Lande ◽  
Carol A. Hirshman
Keyword(s):  
Smooth Muscle ◽  
G Proteins ◽  
Airway Smooth Muscle ◽  
Tracheal Smooth Muscle ◽  
Heterotrimeric G Proteins ◽  
Contractile Responses ◽  
Intracellular Ca ◽  
Increased Sensitivity ◽  
Rho Family

Increased sensitivity to intracellular Ca2+ concentration ([Ca2+]) is an important mechanism for agonist-induced contraction of airway smooth muscle, but the signal transduction pathways involved are uncertain. We studied Ca2+ sensitization with acetylcholine (ACh) and endothelin (ET)-1 in porcine tracheal smooth muscle by measuring contractions at a constant [Ca2+] in strips permeabilized with α-toxin or β-escin. The peptide inhibitor G protein antagonist 2A (GP Ant-2A), which has selectivity for Gq over Gi, inhibited contractile responses to ET-1, ACh, and guanosine 5′- O-(3-thiotriphosphate) (GTPγS), but the proportional inhibition of ACh responses was less than that of ET-1. Pretreatment with pertussis toxin reduced ACh contractions but had no effect on those of ET-1 or GTPγS. Clostridium botulinum C3 exoenzyme, which inactivates Rho family monomeric G proteins, caused similar reductions in contractile responses to ACh, ET-1, and GTPγS. Farnesyltransferase inhibition, which inhibits Ras G proteins, reduced responses to ET-1. We conclude that the heterotrimeric G proteins Gq and Gi both contribute to Ca2+ sensitization by ACh, whereas ET-1 responses involve Gq but not Gi. Both Gq and Gi pathways likely involve Rho family small G proteins. A Ras-mediated pathway also contributes to Ca2+ sensitization by ET-1 in airway smooth muscle.

48-h Hypoxic exposure results in endothelium-dependent systemic vascular smooth muscle cell hyperpolarization

2002 ◽  
Vol 283 (1) ◽  
pp. R79-R85 ◽  
Author(s):  
Scott Earley ◽  
Jay S. Naik ◽  
Benjimen R. Walker
Keyword(s):  
Smooth Muscle ◽  
Membrane Potential ◽  
Vascular Smooth Muscle ◽  
Vessel Wall ◽  
Hypoxic Exposure ◽  
Resting Membrane Potential ◽  
Resistance Arteries ◽  
Adrenergic Agonist ◽  
Intracellular Ca ◽  
Oxide Synthase

Chronic hypoxia (CH) results in reduced sensitivity to vasoconstrictors in conscious rats that persists upon restoration of normoxia. We hypothesized that this effect is due to endothelium-dependent hyperpolarization of vascular smooth muscle (VSM) cells after CH. VSM cell resting membrane potential was determined for superior mesenteric artery strips isolated from CH rats (Pb = 380 Torr for 48 h) and normoxic controls. VSM cells from CH rats studied under normoxia were hyperpolarized compared with controls. Resting vessel wall intracellular Ca2+ concentration ([Ca2+]i) and pressure-induced vasoconstriction were reduced in vessels isolated from CH rats compared with controls. Vasoconstriction and increases in vessel wall [Ca2+]i in response to the α1-adrenergic agonist phenylephrine (PE) were also blunted in resistance arteries from CH rats. Removal of the endothelium normalized resting membrane potential, resting vessel wall [Ca2+]i, pressure-induced vasoconstrictor responses, and PE-induced constrictor and Ca2+ responses between groups. Whereas VSM cell hyperpolarization persisted in the presence of nitric oxide synthase inhibition, heme oxygenase inhibition restored VSM cell resting membrane potential in vessels from CH rats to control levels. We conclude that endothelial derived CO accounts for persistent VSM cell hyperpolarization and vasoconstrictor hyporeactivity after CH.

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