Cyclic nucleotide interactions involved in endothelium-dependent dilatation in rat aortic rings

Grace, Geoffrey C.; Macdonald, Peter S.; Dusting, Gregory J.

doi:10.1016/0014-2999(88)90449-9

Cited by 50 publications

(27 citation statements)

References 22 publications

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“…However, in the rat aorta the relaxations to isoprenaline are inhibited by methylene blue and haemoglobin (Grace et al, 1988), agents known to affect the action of nitric oxide . Therefore, it is possible that in this tissue there is a nitric oxide component to the relaxant response to isoprenaline.…”

Section: Introductionmentioning

confidence: 99%

Novel signal transduction pathway mediating endothelium‐dependent β‐adrenoceptor vasorelaxation in rat thoracic aorta

Gray

Marshall

1992

British J Pharmacology

181

122

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1 Isoprenaline (3 x 10-8-I0-5M), salbutamol (3 x 10-7-10-4M) and forskolin (3 x 10-9-3 x 10-7M) relaxed rat isolated thoracic aortic rings contracted with noradrenaline (10-7 M). Removal of the endothelium from the aortic rings abolished the effect of acetylcholine (10-6 M) and completely prevented the vascular relaxation induced by isoprenaline, salbutamol or forskolin. 2 The isoprenaline concentration-relaxation curve was shifted in parallel to the right about 10 fold by propranolol (3 x 10-7 M) with no change in the maximum response, showing that the relaxation was mediated by a P-adrenoceptor.3 The inhibitor of nitric oxide synthesis, NG-nitro-L-arginine (L-NOARG; 10-5 M), shifted the isoprenaline relaxation curve to the right and reduced the maximum response. 4 Isoprenaline (10-6 M) relaxed noradrenaline-induced tone by approximately 95% and at the same time increased levels of adenosine 3':5'-cyclic monophosphate (cyclic AMP) 4 fold and guanosine 3':5'-cyclic monophosphate (cyclic GMP) 12 fold in the aortic rings. Sodium nitroprusside (3 x 10-8 M) relaxed noradrenaline-evoked tone by 82% without changing levels of cyclic AMP but raised cyclic GMP 19 fold.5 Forskolin (10-7 M) relaxed noradrenaline-induced tone by approximately 41% and, like isoprenaline, increased levels of cyclic AMP (2.5 fold) and cyclic GMP (12 fold) in the aortic rings. 6 Removal of the endothelium abolished the relaxant effects of isoprenaline (10-6 M) and also the associated accumulation of cyclic AMP and cyclic GMP. 7 L-NOARG (10-M) inhibited the relaxant responses and accumulation of cyclic GMP induced by isoprenaline (10-6 M) and forskolin (10-M) without affecting the associated cyclic AMP accumulation.8 It is concluded that, in the rat aorta, isoprenaline acts through a P-adrenoceptor on the endothelium to raise cyclic AMP and that this may, directly or indirectly, release nitric oxide to evoke vascular relaxation via the increase in cyclic GMP. The importance of this novel transduction pathway for cardiovascular regulation remains to be determined.

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Section: Introductionmentioning

confidence: 99%

Novel signal transduction pathway mediating endothelium‐dependent β‐adrenoceptor vasorelaxation in rat thoracic aorta

Gray

Marshall

1992

British J Pharmacology

181

122

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“…In the present experiments, the weak difference in isoprenaline-induced LCX relaxation observed in the absence or presence of endothelium could be attributed to the basal release of guanosine 3':5'-cyclic monophosphate (cyclic GMP) since blockade of the NO pathway by L-NAME resulted in the same slight decrease in maximal relaxation of the vessel. Indeed, synergistic cooperation between cyclic GMP and cyclic AMP has been previously suggested by Grace et al (1988) in the relaxation of rat aorta to isoprenaline.…”

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confidence: 99%

Lack of importance of NO in β‐adrenoceptor‐mediated relaxation of large epicardial canine coronary arteries

Béa¹,

Ghaleh²,

Giudicelli³

et al. 1994

British J Pharmacology

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This study was designed to test the role of endothelium and the L-arginine/NO pathway in the relaxation of canine large coronary. arteries to the P-adrenoceptor agonist, isoprenaline. Relaxation of left circumflex (LCX) and left anterior descending (LAD) coronary arteries were measured in organ baths after contraction with the thromboxane analogue, U46619, either in absence or in presence of endothelium and in LCX arteries after pretreatment with N0-nitro-L-arginine-methyl-ester (L-NAME). LAD arteries with and without endothelium relaxed identically to isoprenaline but their maximal relaxation was smaller than corresponding LCX arteries with endothelium. A slight but non significant difference was observed in LCX arteries with endothelium as compared to rings without endothelium or pretreated with L-NAME. No difference was observed in the relaxation of LCX arteries to forskolin in arteries with or without endothelium. These results suggest that endothelium is not essential and that NO is not directly involved in the relaxation of large coronary arteries induced by isoprenaline.

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“…Growing evidence indicates that a number of classic endotheliumindependent vasodilator drugs also cause endotheliumdependent vasodilation, and this process seems to be related to endothelial NO production. [7][8][9][10][11][12][13][14][15][16][17][18][19] These include (1) the inhibition of isoprenaline-induced vasorelaxation in rat aorta by hemoglobin and methylene blue 11,12 ; (2) the inhibition of prostacyclin-and forskolin-induced vasorelaxation in pig coronary artery in vitro by hemoglobin and methylene blue 13 ; (3) the inhibition of salbutamol-and epinephrine-induced vasorelaxation in vivo and in vitro in the rat by the NO synthase (NOS) inhibitor N -nitro-L-arginine methyl ester (L-NAME); 14 -16 (4) the inhibition of isoproterenol-induced resistance coronary vessel dilation in the conscious dog by L-NAME 17,18 ; and (5) the inhibition of isoproterenol-induced vasodilation in human forearm by N -monomethyl-Larginine. 19 These results indicate that in blood vessels, there is an NO component to the vasorelaxant response to all of See page 729 these agonists.…”

mentioning

confidence: 99%

cAMP Signal Transduction Cascade, a Novel Pathway for the Regulation of Endothelial Nitric Oxide Production in Coronary Blood Vessels

Zhang

Hintze

2001

ATVB

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Abstract-The aim of this study was to determine whether cAMP signal transduction plays a role in the regulation of endothelial nitric oxide (NO) production. Canine coronary blood vessels were isolated, and nitrite, the hydration product of NO, from these vessels was quantified by using the Griess reaction. Forskolin (10 Ϫ4 mol/L), 8-bromo-cAMP (10 Ϫ2 mol/L), or isoproterenol (10 Ϫ4 mol/L) significantly increased nitrite release to 168Ϯ10, 162Ϯ13, or 149Ϯ13 pmol/mg, respectively, from isolated coronary microvessels (all PϽ0.05; control, 86Ϯ3 pmol/mg). Adrenomedullin and calcitonin gene-related peptide (CGRP), both potent vasodilator peptides, also increased coronary microvascular nitrite production. N -nitro-L-arginine methyl ester, a competitive inhibitor of NO synthase, or Rp-cAMP, a protein kinase A inhibitor, markedly blocked the nitrite release induced by these agents. Forskolin and adrenomedullin also potentiated coronary NO production induced by bradykinin. In large coronary arteries, removal of the endothelium eliminated nitrite production to both forskolin and acetylcholine. Our data demonstrate that stimulation of cAMP signal transduction can substantially increase coronary NO production, indicating that there is a cAMP-mediated, endothelial NO-forming system in coronary blood vessels. Because the cAMP signal cascade can be activated by CGRP or adrenomedullin and enhance kinin-mediated nitrite production, the cAMP-NO pathway may play an important role in the regulation of cardiovascular function. Key Words: cAMP Ⅲ nitric oxide Ⅲ endothelium Ⅲ protein kinase B Ⅲ coronary blood vessels ␤ -Adrenoceptor agonists and adenosine have been regarded as "archetypal" endothelium-independent vasodilators that cause vasodilation by increasing intracellular cAMP, with subsequent activation of protein kinase A (PKA) and myosin light-chain kinase within smooth muscle cells. [1][2][3][4][5][6] However, recent studies have challenged this concept. Growing evidence indicates that a number of classic endotheliumindependent vasodilator drugs also cause endotheliumdependent vasodilation, and this process seems to be related to endothelial NO production. [7][8][9][10][11][12][13][14][15][16][17][18][19] These include (1) the inhibition of isoprenaline-induced vasorelaxation in rat aorta by hemoglobin and methylene blue 11,12 ; (2) the inhibition of prostacyclin-and forskolin-induced vasorelaxation in pig coronary artery in vitro by hemoglobin and methylene blue 13 ; (3) the inhibition of salbutamol-and epinephrine-induced vasorelaxation in vivo and in vitro in the rat by the NO synthase (NOS) inhibitor N -nitro-L-arginine methyl ester (L-NAME); 14 -16 (4) the inhibition of isoproterenol-induced resistance coronary vessel dilation in the conscious dog by L-NAME 17,18 ; and (5) the inhibition of isoproterenol-induced vasodilation in human forearm by N -monomethyl-Larginine. 19 These results indicate that in blood vessels, there is an NO component to the vasorelaxant response to all of See page 729 these agonists. This may be of...

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Cyclic nucleotide interactions involved in endothelium-dependent dilatation in rat aortic rings

Cited by 50 publications

References 22 publications

Novel signal transduction pathway mediating endothelium‐dependent β‐adrenoceptor vasorelaxation in rat thoracic aorta

Novel signal transduction pathway mediating endothelium‐dependent β‐adrenoceptor vasorelaxation in rat thoracic aorta

Lack of importance of NO in β‐adrenoceptor‐mediated relaxation of large epicardial canine coronary arteries

cAMP Signal Transduction Cascade, a Novel Pathway for the Regulation of Endothelial Nitric Oxide Production in Coronary Blood Vessels

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