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https://hdl.handle.net/2440/8814
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Type: | Journal article |
Title: | Effects of guanylyl cyclase and protein kinase G inhibitors on vasodilatation in non-tolerant and tolerant bovine coronary arteries |
Author: | de la Lande, I. Stafford, I. Horowitz, J. |
Citation: | European Journal of Pharmacology, 1999; 370(1):39-46 |
Publisher: | ELSEVIER SCIENCE BV |
Issue Date: | 1999 |
ISSN: | 0014-2999 1879-0712 |
Abstract: | The effects in bovine coronary arteries of the soluble guanylyl cyclase inhibitor 1 H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) were examined in order to establish the relative importance of the enzyme (a) in the vasodilator actions of glyceryl trinitrate and S-nitroso-N-acetylpenicillamine and (b) in induction of tolerance to these agents. ODQ strongly inhibited responses to both relaxants with IC50's of the order of 0.5 microM; in contrast, the protein kinase G inhibitor, 8-bromoguanosine-3',5'-monophosphorothioate (Rp-8-Br-cGMPS) had little effect on the responses. Tolerance after pre-incubation with glyceryl trinitrate (10 microM) was unaffected by co-pre-incubation with ODQ (1.0 microM), but similar experiments with S-nitroso-N-acetylpenicillamine were inconclusive because tolerance was associated with depressed contractile activity. It is concluded that in bovine coronary arteries soluble guanylyl cyclase is essential for vasorelaxation to both glyceryl trinitrate and S-nitroso-N-acetylpenicillamine but is unimportant for induction of tolerance to glyceryl trinitrate. Our results add weight to the hypothesis of impaired biotransformation rather than guanylyl cyclase desensitisation as the mechanism of in vitro nitrate tolerance. |
Keywords: | Muscle, Smooth, Vascular Coronary Vessels Animals Cattle Nitroglycerin S-Nitroso-N-Acetylpenicillamine Oxadiazoles Quinoxalines Guanylate Cyclase Cyclic GMP-Dependent Protein Kinases Penicillamine Cyclic GMP Thionucleotides Vasodilator Agents Enzyme Inhibitors Protein Kinase Inhibitors Vasodilation Drug Interactions Drug Tolerance |
DOI: | 10.1016/S0014-2999(99)00092-8 |
Published version: | http://dx.doi.org/10.1016/s0014-2999(99)00092-8 |
Appears in Collections: | Aurora harvest Medicine publications |
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