Relaxation of guinea‐pig trachea by sodium nitroprusside: cyclic GMP and nitric oxide not involved

Sadeghi-Hashjin, G.; Folkerts, Gert; Henricks, Paul A.J.; Loo, Peet G.F. van de; Dik, Ilse E.M.; Nijkamp, Frans P.

doi:10.1111/j.1476-5381.1996.tb15426.x

Cited by 17 publications

(12 citation statements)

References 22 publications

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“…We also found that IBMX had no signi®cant eect on the relaxation of the rabbit aorta to NO. A similar dissociation in cyclic GMP levels and relaxation in the presence and absence of zaprinast has been noted in respiratory smooth muscle (Sadeghi-hashjin et al, 1996).…”

Section: Role Of Phosphodiesterase In the Response To Nosupporting

confidence: 73%

Evidence that additional mechanisms to cyclic GMP mediate the decrease in intracellular calcium and relaxation of rabbit aortic smooth muscle to nitric oxide

Weisbrod

Griswold

Yaghoubi

et al. 1998

British J Pharmacology

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1 The role of cyclic GMP in the ability of nitric oxide (NO) to decrease intracellular free calcium concentration [Ca 2+ ] i and divalent cation in¯ux was studied in rabbit aortic smooth muscle cells in primary culture. In cells stimulated with angiotensin II (AII, 10 77 M), NO (10 710 ± 10 76 M) increased cyclic GMP levels measured by radioimmunoassay and decreased [Ca 2+ ] i and cation in¯ux as indicated by fura-2¯uorimetry. 2 Zaprinast (10 74 M), increased NO-stimulated levels of cyclic GMP by 3 ± 20 fold. Although the phosphodiesterase inhibitor lowered the level of [Ca 2+ ] i reached after administration of NO, the initial decreases in [Ca 2+ ] i initiated by NO were not signi®cantly dierent in magnitude or duration from those that occurred in the absence of zaprinast. ] i or cation in¯ux caused by higher concentrations of NO (10 77 ± 10 76 M) were unaected. Relaxation of intact rabbit aorta rings to NO (10 77 ± 10 75 M) also persisted in the presence of ODQ without a signi®cant increase in cyclic GMP. Rp-8-Br-cyclic GMPS blocked the decreases in cation in¯ux caused by a cell permeable cyclic GMP analog, but ODQ and/or the protein kinase G inhibitor had no signi®cant eect on the decrease caused by NO. 4 Although inhibitors of cyclic GMP, protein kinase G and phosphodiesterase can be shown to aect the decrease in [Ca 2+ ] i and cation in¯ux via protein kinase G, these studies indicate that when these mechanisms are blocked, cyclic GMP-independent mechanisms also contribute signi®cantly to the decrease in [Ca 2+ ] i and smooth muscle relaxation to NO.

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Section: Role Of Phosphodiesterase In the Response To Nosupporting

confidence: 73%

Evidence that additional mechanisms to cyclic GMP mediate the decrease in intracellular calcium and relaxation of rabbit aortic smooth muscle to nitric oxide

Weisbrod

Griswold

Yaghoubi

et al. 1998

British J Pharmacology

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“…This metabolic activation might indeed be mediated by distinct NO-generating enzymes for each of the chemical classes of compounds, which even may be organ-specific (Kowaluk et al 1992;Gordge et al 1998). There are also data indicating that elevations in tissue cGMP levels do not always explain relaxation induced by NO donors (Kuenzli et al 1996;Sadeghi-Hashjin et al 1996), and the involvement of direct effects, such as S-nitrosylation reactions with protein thiols (Arnelle and Stamler 1995;Perkins et al 1998) or even NO-independent effects (Sadeghi-Hashjin et al 1996), has been suggested. In light of these discrepancies, it is becoming obvious that data obtained using a certain agent should not be extrapolated to other compounds and it is essential to examine the mechanism of action of each chemically distinct nitrocompound in each tissue, comparing it with that of NO itself.…”

Section: Introductionmentioning

confidence: 97%

Differential mechanisms of urethral smooth muscle relaxation by several NO donors and nitric oxide

Garcia-Pascual¹,

Costa²,

Labadía³

et al. 1999

Naunyn-Schmiedeberg's Archives of Pharmacology

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We have examined the mechanisms of action of a broad spectrum of nitric oxide (NO) donors, including several S-nitrosothiols, sodium nitroprusside (SNP) and nitroglycerine (GTN), in relation to their relaxant activity of urethral smooth muscle. For all the compounds examined, NO release (in solution and in the presence of urethral tissue), relaxation responses, elevations in cGMP levels and the effect of thiol modulators were evaluated and compared with the effect of NO itself. Whilst all NO donors, except GTN, released NO in solution due to photolysis or chemical catalysis, this release was not correlated with their relaxant activity in sheep urethral preparations, which were furthermore not affected by the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (cPTIO; 0.3 mM). A substantial NO-generating activity was found for S-nitroso-L-cysteine (CysNO) and S-nitroso-N-acetyl-D,L-penicillamine (SNAP) in the presence of urethral cytosolic fractions, suggesting metabolic activation to NO in the cytosol of the target tissue. In contrast, NO generation from S-nitroso-N-acetyl-L-cysteine (N-ac-CysNO), S-nitrosoglutathione (GSNO) and SNP were reduced by the presence of urethral homogenate and/or subcellular fractions, suggesting direct NO transfer to tissue constituents. NO donors and NO gas induced dissimilar degrees of cGMP accumulation in urethral tissue, while they were essentially equipotent as urethral relaxants. Furthermore, 1H-[1,2,4] -oxadiazole-[4,3-a]-quinoxalin-1-one (ODQ; 10 microM) inhibited both relaxation and cGMP accumulations, but with different potency for the different compounds. Oxidation of sarcolemmal thiol groups with 5-5'-dithio-bis[2-nitrobenzoic acid] (DTNB; 0.5 mM) enhanced relaxations to GSNO, an effect that was reversed by dithiotreitol (DTT; 1 mM), suggesting a direct effect through nitrosylation/oxidation reactions at the cell membrane, while relaxations to NO and to all the other compounds were not affected by these treatments. Finally, photodegradation of SNP induced the formation of a stable intermediate that still evoked NO-cGMP-mediated relaxations. This indicates that the assumption that SNP is fully depleted of NO by exposure to light should be revised. It can be concluded that important differences exist in the mechanisms by which distinct NO donors relax urethral smooth muscle and they cannot be regarded simply as NO-releasing prodrugs.

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“…This suggests that tissues in both phenotypes have enough guanylate cyclase present to fully relax them and therefore it is the lack of enough NO being released which is the deficiency in the response to carbachol in the db/db mouse. However, the use of SNP as an NO donor is controversial [26].…”

Section: Effects Of Carbachol and Snp On Phenylephrine-induced Contramentioning

confidence: 99%

A Comparison of Spasmogenic and Relaxant Responses in Aortae from C57/BL/KsJ Diabetic Mice with Those from Their Non-Diabetic Litter Mates

Piercy

Taylor²

1998

Pharmacology

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We have investigated the responsiveness of thoracic aorta from the C57/BL/KsJ-db/db mouse (a model of type II diabetes) using a small-vessel myograph. The maximum tension developed in response to phenylephrine was greater in diabetic mice compared with non-diabetic (+/?) mice (2.7 ± 0.1 and 1.8 ± 0.1 mN/mm, respectively). Responses to phenylephrine were enhanced in tissues from both phenotypes when pre-incubated with L-NAME (100 µmol/l) and after the addition of oxyhaemoglobin (3 µmol/l), suggesting that endogenous NO release occurs in both. The maximum relaxation to carbachol was less in db/db mice (32 ± 4%) than in +/? mice (49 ± 5%) whilst that to sodium nitroprusside was similar (>90%). However, the concentration-effect curve to both vasorelaxants in db/db mice lay to the right of that in the +/? mice. These results suggest that the responsiveness of the vasculature is altered in the db/db mouse. Since this mouse is a model of type II diabetes this may be a consequence of hyperglycaemia and/or insulin resistance.

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Relaxation of guinea‐pig trachea by sodium nitroprusside: cyclic GMP and nitric oxide not involved

Cited by 17 publications

References 22 publications

Evidence that additional mechanisms to cyclic GMP mediate the decrease in intracellular calcium and relaxation of rabbit aortic smooth muscle to nitric oxide

Evidence that additional mechanisms to cyclic GMP mediate the decrease in intracellular calcium and relaxation of rabbit aortic smooth muscle to nitric oxide

Differential mechanisms of urethral smooth muscle relaxation by several NO donors and nitric oxide

A Comparison of Spasmogenic and Relaxant Responses in Aortae from C57/BL/KsJ Diabetic Mice with Those from Their Non-Diabetic Litter Mates

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