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A comparison of vasodilator activity of agents activating cyclic nucleotides with those inhibiting their metabolism in rabbit isolated ear artery
Author(s) -
Wood L.M.,
Owen D.A.A.
Publication year - 1989
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1989.tb11873.x
Subject(s) - zaprinast , ibmx , endocrinology , sodium nitroprusside , medicine , vasodilation , phosphodiesterase inhibitor , forskolin , cyclic nucleotide , chemistry , phosphodiesterase , adenosine , stimulation , biology , biochemistry , nitric oxide , nucleotide , gene , enzyme
1 The effects of forskolin, a direct activator of adenylate cyclase and sodium nitroprusside, a direct activator of guanylate cyclase, were studied on rabbit isolated ear arteries preconstricted with 80 m m potassium. 2 Bolus injection of these two compounds resulted in vasodilatation. They had similar potencies in this tissue but forskolin had a significantly longer duration of action than sodium nitroprusside. 3 In the same tissue, perfusion with isobutylmethylxanthine (IBMX), a non‐selective phosphodiesterase (PDE) inhibitor, or zaprinast, selective for the PDE primarily responsible for the metabolism of guanosine 3′:5′‐cyclic monophosphate (cyclic GMP), resulted in vasodilatation. However, SK&F 94120 selective for cyclic AMP‐PDE (PDE III), primarily responsible for the metabolism of adenosine 3′:5′‐cyclic monophosphate (cyclic AMP), resulted in vasodilatation only at very high concentrations. The rank order of potency for the compounds was IBMX > zaprinast > SK&F 94120. 4 The effects of these three PDE inhibitors were studied on the vasoconstriction produced by perivascular sympathetic nerve stimulation in the absence of raised potassium. IBMX and zaprinast, caused a reduction in the response at 50 Hz stimulation frequency and a shift in the frequency‐response curve to the right. SK&F 94120 did not displace the frequency‐response curve but did reduce the response at 50 Hz. The same order of potency for the inhibition of the vasoconstrictor responses to perivascular sympathetic nerve stimulation was found as for vasodilatation i.e. IBMX > zaprinast > SK&F 94120. 5 These results indicate that in the same tissue direct activation of adenylate and guanylate cyclase results in vasodilatation. Non‐specific PDE and cyclic GMP‐PDE inhibition also resulted in vasodilatation and inhibition of vasoconstrictor responses to sympathetic nerve stimulation. However a selective cyclic AMP‐PDE (PDE III) inhibitor did not result in vasodilatation, except at very high concentrations, or inhibit sympathetic vasoconstrictor responses except to reduce the response at 50 Hz stimulation. These findings provide further support for the ability of PDE inhibitors to be tissue selective.