Please use this identifier to cite or link to this item: 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: Behavioural Processes, 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
Appears in Collections:Aurora harvest
Medicine publications

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