Cyclic Nucleotides and Blood Vessel Contraction

Kramer, G. L.; Hardman, Joel G.

doi:10.1002/cphy.cp020208

Cited by 18 publications

(16 citation statements)

References 101 publications

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“…In contrast to contraction, relaxation is believed to be brought about by the lowering of cytoplasmic Ca2+ concentrations (Kramer & Hardman, 1980). The present study shows that the [Ca2+]i is decreased by Iso in normal media, accompanied by a relaxation.…”

Section: Multiple Mechanisms Of Relaxant Actions Of Isoprenaline In Rmentioning

confidence: 99%

“…The present study shows that the [Ca2+]i is decreased by Iso in normal media, accompanied by a relaxation. The relaxant effect of 16-adrenoceptor agonists involves cyclic AMP (Takayanagi et al, 1972;Kramer & Hardman, 1980), which is reported to stimulate Ca2+ uptake by the Ca2+ store (Kramer & Hardman, 1980), to inhibit Ca2 + influx (Meisheri & van Breemen, 1982) and to inhibit the contractile system directly (Adelstein & Hathaway, 1979;Itoh et al, 1982;Morgan & Morgan, 1984). If stimulation of Ca2+ uptake by the ryanodine-sensitive Ca2+ store is a main cause of Iso-induced relaxation, the relaxation should be abolished or greatly reduced by ryanodine, since the drug blocks the function of the ryanodinesensitive Ca2+ store.…”

Section: Multiple Mechanisms Of Relaxant Actions Of Isoprenaline In Rmentioning

confidence: 99%

“…One possible mechanism of vasodilatation is the increased Ca2+ uptake by the Ca2+ store and the Ca2+ sinks (Kramer & Hardman, 1980). The relaxing effect of f-adrenoceptor agonists involves adenosine 3': 5'-cyclic monophosphate (cyclic AMP) (Takayanagi et al, 1972;Kramer & Hardman, 1980), and cyclic AMP stimulates 45Ca2+ uptake by smooth muscle microsomes (Fitzpatrick & Szentivanyi, 1977, Hisayama & Takayanagi, 1983Raeymaekers et al, 1988).…”

Section: Introductionmentioning

confidence: 99%

“…The relaxing effect of f-adrenoceptor agonists involves adenosine 3': 5'-cyclic monophosphate (cyclic AMP) (Takayanagi et al, 1972;Kramer & Hardman, 1980), and cyclic AMP stimulates 45Ca2+ uptake by smooth muscle microsomes (Fitzpatrick & Szentivanyi, 1977, Hisayama & Takayanagi, 1983Raeymaekers et al, 1988). However, few studies have critically evaluated the cause-effect relationship between the increased Ca2+ uptake by the stores and relaxation in intact smooth muscle preparations (Morgan & Morgan, 1984).…”

Section: Introductionmentioning

confidence: 99%

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Ryanodine reveals multiple contractile and relaxant mechanisms in vascular smooth muscle: simultaneous measurements of mechanical activity and of cytoplasmic free Ca²⁺ level with fura‐2

Hisayama

Takayanagi

Okamoto

1990

British J Pharmacology

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1 The effects of ryanodine on changes in cytoplasmic Ca2+ level ([Ca2+]i) and muscle tension induced by maximum concentrations of phenylephrine (Phe; 1 pM), prostaglandin F2, (PGF2,, 10UM), caffeine (Caf, 30 mM) and isoprenaline (Iso, 1 M) were examined in rat aortic strips using fura-2. Treatment of the preparation with ryanodine had no effect on the concentration-response curves for Iso in relaxing the 0.1 M Phe-or 40 mm K+-induced precontraction.7 It is suggested that Phe and Caf mobilize Ca2 + from a ryanodine-sensitive Ca2 + store and that PGF2.releases Ca2+ from a ryanodine-insensitive Ca2+ store. The former contributes to the transient contraction through a Ca2'-dependent process, while the latter seems not to be directly associated with the contraction. The sustained contraction under Ca2 +-free conditions might involve a Ca2 '-independent process or a change in the sensitivity of the contractile filaments to Ca2 + 8 In addition to lowering cytoplasmic Ca2+ concentration, it is suggested that Iso counteracts the apparently Ca2 +-independent process. The ryanodine-sensitive Ca2+ store plays no substantial role in active relaxation by Iso, although it does play a major role in the maintenance of cytoplasmic Ca2+ in a quiescent muscle.

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Section: Multiple Mechanisms Of Relaxant Actions Of Isoprenaline In Rmentioning

confidence: 99%

Section: Multiple Mechanisms Of Relaxant Actions Of Isoprenaline In Rmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Ryanodine reveals multiple contractile and relaxant mechanisms in vascular smooth muscle: simultaneous measurements of mechanical activity and of cytoplasmic free Ca²⁺ level with fura‐2

Hisayama

Takayanagi

Okamoto

1990

British J Pharmacology

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“…In vascular smooth muscle cells, A-adrenoceptor stimulation or forskolin-induced activation by adenylyl cyclase are associated with an increase in the intracellular level of cyclic AMP (Kramer & Hardman, 1980) and with relaxation, but the precise mechanism by which the cyclic nucleotide causes relaxation is not clear. Cyclic AMP is also operative in perivascular sympathetic nerve endings where it modulates neurotransmitter release.…”

Section: Introductionmentioning

confidence: 99%

Effects of cyclic AMP and analogues on neurogenic transmission in the rat tail artery

Ouédraogo¹,

Stoclet²,

Bucher³

1994

British J Pharmacology

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1 The effects of two 8-substituted analogues of adenosine 3':5'-cyclic monophosphate (cyclic AMP) were compared with those of forskolin and isoprenaline on [3H]-noradrenaline release and vasoconstriction induced by electrical field stimulation (24 pulses at 0.4 Hz, 200 mA, 0.3 ms duration) in the rat tail artery, in the absence and in the presence of protein kinase inhibitors.2 8-Bromo-adenosine 3':5'-cyclic monophosphate (8-bromo-cyclic AMP, 10-300 tiM), 8-(4-chlorophenylthio)-adenosine 3':5' cyclic monophosphate (8-pCPT-cycic AMP, 3-300 pM), forskolin (0.3-10 tiM) and isoprenaline (1 nM-I1LM) all concentration-dependently enhanced stimulation-induced [3H]-noradrenaline release. The effect of cyclic AMP analogues was larger (2.5 fold at 300 flM) than those of cyclic AMP elevating drugs (1.6 fold at 10 M for forskolin and 1.5 fold at 30 nM for isoprenaline). 3 At concentrations active at the prejunctional level, the four drugs had differential effects on stimulation-induced vasoconstriction, which was enhanced by the two cyclic AMP analogues, decreased by forskolin and not significantly altered by isoprenaline. By contrast they were unaffected by the cyclic GMP-dependent protein kinase (PKG) inhibitor, 8-bromo-guanosine 3':5'-cyclic monophosphorothioate, Rp-isomer (Rp-8-bromo-cyclic GMPS; 10WM). At the same concentrations the PKA inhibitor attenuated only the nerve-induced vasoconstrictor responses obtained in the presence of 8-bromo-cyclic AMP, whereas the PKG inhibitor did not modify that obtained in the presence of 8-bromo-cycic AMP or forskolin.5 Exposure to the protein kinase C (PKC) activator, phorbol 12-myristate 13-acetate (1 jM) enhanced nerve-evoked [3H]-noradrenaline release, and this effect was decreased by the PKC inhibitor, 2-[1-(3-dimethylaminopropyl)-indol-3-yl]-3-(-indol-3-yl)-maleimide (GF 109203X; 100 nM). However, the latter drug did not modify the enhancing effect of 8-bromo-cyclic AMP on [3H]-noradrenaline release. 6 It is concluded that activation of cyclic AMP-dependent protein kinase is involved in the enhancing effect of cyclic AMP-elevating compounds on prejunctional release of noradrenaline. In addition the results provide no clear-cut evidence for a vasodilator role of PKA.

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Cardiovascular pharmacology of the cardiotonic, imazodan (Cl‐914)

Evans¹,

Potoczak²,

Steffen³

et al. 1986

Drug Development Research

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of the cardiotonic, imazodan (CI-914). Drug Dev. Res. 9:143-157, 1986. lmazodan is a novel pyridazinone derivative. It was evaluated in excised cardiac tissue, anesthetized dogs and monkeys, and conscious dogs. Imazodan, 10-5-10-3M, produced dose-dependent increases in guinea pig atrial and rabbit papillary muscle contractility. In anesthetized dogs and rhesus monkeys, imazodan, 0.001-1 .O mg/kg IV, produced dosedependent increases of 10-150% in myocardial contractility (dPldt max of left ventricular pressure), and decreases of 1-31% in aortic blood pressure. Heart rate increases were minimal (0-34%) in comparison to the changes in contractility and they occurred only at the higher doses. The positive inotropic action of imazodan was not blocked by @-adrenoceptor blockade with propranolol. Forelimb perfusion studies in the anesthetized dog demonstrated that imazodan produces a dose-dependent direct peripheral vasodilator action. This agent was also demonstrated to be a highly effective cardiotonic when administered orally (0.1-1 .O mg/kg) to conscious dogs. The results of these studies indicate that imazodan is an orally effective cardiotonic that possesses balanced positive inotrophic and peripheral vasodilator activities and possesses a wide margin of cardiac safety.

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Cyclic Nucleotides and Blood Vessel Contraction

Cited by 18 publications

References 101 publications

Ryanodine reveals multiple contractile and relaxant mechanisms in vascular smooth muscle: simultaneous measurements of mechanical activity and of cytoplasmic free Ca²⁺ level with fura‐2

Ryanodine reveals multiple contractile and relaxant mechanisms in vascular smooth muscle: simultaneous measurements of mechanical activity and of cytoplasmic free Ca²⁺ level with fura‐2

Effects of cyclic AMP and analogues on neurogenic transmission in the rat tail artery

Cardiovascular pharmacology of the cardiotonic, imazodan (Cl‐914)

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Cyclic Nucleotides and Blood Vessel Contraction

Cited by 18 publications

References 101 publications

Ryanodine reveals multiple contractile and relaxant mechanisms in vascular smooth muscle: simultaneous measurements of mechanical activity and of cytoplasmic free Ca2+ level with fura‐2

Ryanodine reveals multiple contractile and relaxant mechanisms in vascular smooth muscle: simultaneous measurements of mechanical activity and of cytoplasmic free Ca2+ level with fura‐2

Effects of cyclic AMP and analogues on neurogenic transmission in the rat tail artery

Cardiovascular pharmacology of the cardiotonic, imazodan (Cl‐914)

Contact Info

Product

Resources

About

Ryanodine reveals multiple contractile and relaxant mechanisms in vascular smooth muscle: simultaneous measurements of mechanical activity and of cytoplasmic free Ca²⁺ level with fura‐2

Ryanodine reveals multiple contractile and relaxant mechanisms in vascular smooth muscle: simultaneous measurements of mechanical activity and of cytoplasmic free Ca²⁺ level with fura‐2