Nitroglycerine‐ and isoprenaline‐induced vasodilatation: assessment from the actions of cyclic nucleotides

Nitroglycerine‐ and isoprenaline‐induced vasodilatation: assessment from the actions of... 1 To investigate the vasodilator actions of nitroglycerine and isoprenaline, the effects of these agents, dibutyryl cyclic AMP (db cyclic AMP) and 8‐bromo cyclic GMP (8‐Br cyclic GMP) on intact muscle tissue, and of cyclic AMP and cyclic GMP on skinned muscle of the rabbit mesenteric artery were investigated. 2 In porcine coronary artery, nitroglycerine (>0.1 μm) increased the production of cyclic GMP with no change in the amount of cyclic AMP, while isoprenaline (>0.1 μm) significantly increased the production of cyclic AMP with no change in the amount of cyclic GMP. 3 In the rabbit mesenteric artery, nitroglycerine or isoprenaline inhibited the tonic component of the 39 mm (K)o‐induced contraction to a greater extent than the phasic component. Nitroglycerine and 8‐Br cyclic GMP showed a stronger inhibitory action on the K‐induced contraction than did isoprenaline and db cyclic AMP. 4 The sources of Ca utilized for the generation of contraction by noradrenaline and caffeine were estimated to be the same as those determined from the amplitudes of contractions evoked in Ca‐free solution by various concentrations of noradrenaline or caffeine. 5 In intact muscle tissues, the effects of nitroglycerine or 8‐Br cyclic GMP on the amount of Ca stored in cells were estimated from the caffeine‐induced contraction in Ca‐free solution. Both agents inhibited the contractions due to a reduction in the amount of Ca in the cells. When the effects of isoprenaline or db cyclic AMP were observed, both agents inhibited the caffeine‐induced contraction but the accumulation of Ca into cells was greater than the control. 6 In saponin skinned muscles, the pCa‐tension relationship in the presence of cyclic AMP and cyclic AMP‐dependent protein kinase (cyclic AMP‐PK) shifted to the right and to a lower level in comparison with the control. Applications of cyclic GMP with cyclic GMP‐dependent protein kinase (cyclic GMP PK) also inhibited the contraction induced by low concentrations of Ca. 7 In skinned muscles, cyclic AMP exhibited dual actions on Ca store sites, i.e. in the presence of high concentrations of Ca or prolonged superfusion of Ca, cyclic AMP reduced the amount of Ca due to activation of the Ca‐induced Ca release mechanism by excess accumulation of Ca. On the other hand, cyclic GMP consistently inhibited the amplitude of the caffeine‐induced contraction due to a reduction in the amount of Ca in the store sites. 8 These results indicate that nitroglycerine and isoprenaline increase the amount of cyclic GMP and cyclic AMP, respectively. The main effect of cyclic GMP is activation of Ca extrusion, thus reducing the amount of Ca stored in the cell, while the main effect of cyclic AMP is to increase the amount of Ca stored in the cell. Both cyclic AMP with cyclic AMP‐PK and cyclic GMP with cyclic GMP‐PK inhibit the phosphorylation of myosin. Consequently both cyclic nucleotides reduce the free Ca in the myoplasm and promote relaxation, but by different mechanisms. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png British Journal of Pharmacology Wiley

Nitroglycerine‐ and isoprenaline‐induced vasodilatation: assessment from the actions of cyclic nucleotides

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Publisher
Wiley
Copyright
1985 British Pharmacological Society
ISSN
0007-1188
eISSN
1476-5381
DOI
10.1111/j.1476-5381.1985.tb12923.x
Publisher site
See Article on Publisher Site

Abstract

1 To investigate the vasodilator actions of nitroglycerine and isoprenaline, the effects of these agents, dibutyryl cyclic AMP (db cyclic AMP) and 8‐bromo cyclic GMP (8‐Br cyclic GMP) on intact muscle tissue, and of cyclic AMP and cyclic GMP on skinned muscle of the rabbit mesenteric artery were investigated. 2 In porcine coronary artery, nitroglycerine (>0.1 μm) increased the production of cyclic GMP with no change in the amount of cyclic AMP, while isoprenaline (>0.1 μm) significantly increased the production of cyclic AMP with no change in the amount of cyclic GMP. 3 In the rabbit mesenteric artery, nitroglycerine or isoprenaline inhibited the tonic component of the 39 mm (K)o‐induced contraction to a greater extent than the phasic component. Nitroglycerine and 8‐Br cyclic GMP showed a stronger inhibitory action on the K‐induced contraction than did isoprenaline and db cyclic AMP. 4 The sources of Ca utilized for the generation of contraction by noradrenaline and caffeine were estimated to be the same as those determined from the amplitudes of contractions evoked in Ca‐free solution by various concentrations of noradrenaline or caffeine. 5 In intact muscle tissues, the effects of nitroglycerine or 8‐Br cyclic GMP on the amount of Ca stored in cells were estimated from the caffeine‐induced contraction in Ca‐free solution. Both agents inhibited the contractions due to a reduction in the amount of Ca in the cells. When the effects of isoprenaline or db cyclic AMP were observed, both agents inhibited the caffeine‐induced contraction but the accumulation of Ca into cells was greater than the control. 6 In saponin skinned muscles, the pCa‐tension relationship in the presence of cyclic AMP and cyclic AMP‐dependent protein kinase (cyclic AMP‐PK) shifted to the right and to a lower level in comparison with the control. Applications of cyclic GMP with cyclic GMP‐dependent protein kinase (cyclic GMP PK) also inhibited the contraction induced by low concentrations of Ca. 7 In skinned muscles, cyclic AMP exhibited dual actions on Ca store sites, i.e. in the presence of high concentrations of Ca or prolonged superfusion of Ca, cyclic AMP reduced the amount of Ca due to activation of the Ca‐induced Ca release mechanism by excess accumulation of Ca. On the other hand, cyclic GMP consistently inhibited the amplitude of the caffeine‐induced contraction due to a reduction in the amount of Ca in the store sites. 8 These results indicate that nitroglycerine and isoprenaline increase the amount of cyclic GMP and cyclic AMP, respectively. The main effect of cyclic GMP is activation of Ca extrusion, thus reducing the amount of Ca stored in the cell, while the main effect of cyclic AMP is to increase the amount of Ca stored in the cell. Both cyclic AMP with cyclic AMP‐PK and cyclic GMP with cyclic GMP‐PK inhibit the phosphorylation of myosin. Consequently both cyclic nucleotides reduce the free Ca in the myoplasm and promote relaxation, but by different mechanisms.

Journal

British Journal of PharmacologyWiley

Published: Feb 1, 1985

References

  • Regulation and kinetics of the actin‐myosin‐ATP interaction
    ADELSTEIN, ADELSTEIN; EISENBERG, EISENBERG
  • Role of cyclic AMP in rat aortic microsomal phosphorylation and calcium uptake
    BHALLA, BHALLA; WEBB, WEBB; SINGH, SINGH; BROCK, BROCK
  • Actions of nitroglycerine on the membrane and mechanical properties of smooth muscles of the coronary artery of the pig
    ITO, ITO; KITAMURA, KITAMURA; KURIYAMA, KURIYAMA
  • Nitroglycerine and catecholamine actions on smooth muscle cells of the canine coronary artery
    ITO, ITO; KITAMURA, KITAMURA; KURIYAMA, KURIYAMA
  • Excitation‐contraction coupling in smooth muscle cells of the guinea‐pig mesenteric artery
    ITOH, ITOH; KURIYAMA, KURIYAMA; SUZUKI, SUZUKI
  • Differences and similarities in the noradrenaline‐ and caffeine‐induced mechanical responses in the rabbit mesenteric artery
    ITOH, ITOH; KURIYAMA, KURIYAMA; SUZUKI, SUZUKI
  • Mechanisms of the nitroglycerine‐induced vasodilation in vascular smooth muscles of the rabbit and pig
    ITOH, ITOH; KURIYAMA, KURIYAMA; UENO, UENO

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