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EFFECT OF cGMP INHIBITORS ON THE ACTIONS OF NITRODILATORS IN RAT AORTA

van der Zypp, Andrea ; Majewski, Henryk

Clinical and experimental pharmacology & physiology, 1998-01, Vol.25 (1), p.38-43 [Periódico revisado por pares]

Oxford, UK: Blackwell Publishing Ltd

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Título:
EFFECT OF cGMP INHIBITORS ON THE ACTIONS OF NITRODILATORS IN RAT AORTA
Autor: van der Zypp, Andrea ; Majewski, Henryk
Assuntos: Alkaloids - pharmacology ; Animals ; Aorta, Thoracic - drug effects ; Aorta, Thoracic - physiology ; Carbazoles ; cGMP ; Cyclic GMP - analogs & derivatives ; Cyclic GMP - antagonists & inhibitors ; Cyclic GMP - pharmacology ; Cyclic GMP-Dependent Protein Kinase Type I ; Cyclic GMP-Dependent Protein Kinases - antagonists & inhibitors ; glyceryltrinitrate ; Guanylyl Imidodiphosphate - antagonists & inhibitors ; Indoles ; KT 5823 ; Male ; nitric oxide ; Nitroprusside - pharmacology ; ODQ ; protein kinase G ; r(p) 8-bromoguanosine cyclic monophosphothioate ; Rats ; Rats, Sprague-Dawley ; SNAP ; sodium nitroprusside ; Thionucleotides ; vascular smooth muscle ; Vasodilator Agents - pharmacology
É parte de: Clinical and experimental pharmacology & physiology, 1998-01, Vol.25 (1), p.38-43
Notas: istex:4145B69A836F973E2EC4E7C5D76895A2C7260A9D
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Descrição: SUMMARY 1. The involvement of cGMP in vasodilatation produced by a range of nitrodilators was investigated using two different protein kinase G inhibitors, r(p) 8‐bromoguanosine‐3′5′‐cyclic monophosphothioate (RBrcGMPS) and KT5823. 2. The nitric oxide donors sodium nitroprusside (SNP), glyceryltrinitrate (GTN) and s‐nitroso‐acetylpenicillamine (SNAP), the endothelium‐dependent vasodilator acetylcholine (ACh) as well as the cGMP analogues 8‐(4‐chlorophenylthio)‐cGMP (CPTcGMP) and β‐phenyl‐1‐N2‐etheno‐8‐bromo‐cGMP (PETcGMP) all relaxed rat aortic rings preconstricted with phenylephrine (0.1 μmol/L). 3. The protein kinase G inhibitor KT 5823 (10 μmol/L) produced a very small inhibition of the vasodilatation produced by GTN, but had no effect against vasodilatation produced by SNP, CPTcGMP or PETcGMP, which suggests that KT 5823 is not a useful tool in this system. 4. In contrast, RBrcGMPS (0.5 mmol/L) produced a rightward shift of the concentration‐response curves to SNP, CPTcGMP and PETcGMP. RBrcGMPS (0.5 mmol/L) also completely abolished vasodilatation to ACh and GTN but, surprisingly, had no effect on vasodilatation produced by SNAP. 5. The guanylate cyclase inhibitor 1H‐[1,2,4] oxadiazolo[4,3‐a]quinoxalin‐1‐one (ODQ; 1 and 10 μmol/L) completely inhibited the relaxation produced by GTN, whereas SNAP still had an appreciable relaxant effect after ODQ (1 μmol/L). 6. The differential effect of RBrcGMPS and ODQ on the nitrodilators suggests that there are differences in the mechanism of dilatation between the nitrodilators.
Editor: Oxford, UK: Blackwell Publishing Ltd
Idioma: Inglês

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EFFECT OF cGMP INHIBITORS ON THE ACTIONS OF NITRODILATORS IN RAT AORTA

van der Zypp, Andrea ; Majewski, Henryk

Oxford, UK: Blackwell Publishing Ltd

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