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)
Svensjö
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Dept. Pharmacology, Astra Draco, Lund, Sweden.
Andersson
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Bouskela
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Cyrino
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FZ
Lindgren
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D000818:Animals; D001160:Arterioles / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects*; D002610:Cheek; D006224:Cricetinae; D016650:Fluorescein-5-isothiocyanate; D008297:Male; D008647:Mesocricetus; D020105:Milrinone; D009061:Mouth Mucosa / Q000187:drug effects*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011728:Pyridones / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D020889:Rolipram; D013726:Terbutaline / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
D010726:Phosphodiesterase Inhibitors; D011728:Pyridones; D011760:Pyrrolidinones; D014665:Vasodilator Agents; D016650:Fluorescein-5-isothiocyanate; D020105:Milrinone; D020889:Rolipram; D013726:Terbutaline; D001920:Bradykinin