Effects of two vasodilatory phosphodiesterase inhibitors on bradykinin-induced permeability increase in the hamster cheek pouch

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Abstract
Two inhibitors with selective effect on cyclic nucleotide phosphodiesterases (PDEs, preferentially hydrolyzing cAMP), milrinone (cGMP-inhibited PDE) and rolipram (cAMP-specific PDE) were studied for their effects on bradykinin-induced plasma leakage in comparison with the β2-receptor stimulant terbutaline. The dilation of arterioles induced by milrinone and rolipram was studied in the concentration range 10−7–10−4M. Maximal arteriolar dilation was 53% for milrinone at 10−4M and 28% for rolipram at 10−4M. The hamster cheek pouch preparation was used as prepared for intravital microscopy of fluorescein-labelled dextran, FITC-dextran. Bradykinin was applied topically to the cheek pouch at a final concentration of 4×10−7M and caused rapid and reversible increase in plasma leakage (number of leakage sites) from postcapillary venules. Milrinone (M), rolipram (R) and terbutaline (T) were also applied topically starting 5 min prior to bradykinin application and at final concentration of 10−4 and 10−5M (M), 10−5 and 10−6M (R) and 10−7M (T). These local concentrations resulted in significant (p2-receptor agonists and that the potency of these two PDE inhibitors to counteract plasma leakage was not correlated to their potency as vasodilators.

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