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

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 beta 2-receptor stimulant terbutaline. The dilation of arterioles induced by milrinone and rolipram was studied in the concentration range 10(-7)-10(-4) M. Maximal arteriolar dilation was 53% for milrinone at 10(-4) M and 28% for rolipram at 10(-4) M. 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 x 10(-7) M 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(-5) M (M), 10(-5) and 10(-6) M (R) and 10(-7) M (T). These local concentrations resulted in significant (p < 0.05) and reversible inhibition of the bradykinin-induced response by 44% and 33% (M), 77% and 67% (R) and 46% (T). Combining M and R individually with T resulted in a significantly larger inhibition of the bradykinin response than with each of the drugs given separately.(ABSTRACT TRUNCATED AT 250 WORDS)