HETEROGENEITY OF THE INHIBITORY INFLUENCE OF SULFONYLUREAS ON PROSTANOID-INDUCED SMOOTH-MUSCLE CONTRACTION

In addition to their hypoglycemic influence, sulfonylureas have been r eported to inhibit prostanoid-induced vasoconstriction. Using isometri c tension measurements we investigated whether this inhibitory influen ce is exerted by different sulfonylureas in various types of blood ves sels from different species and in other types of smooth muscle cells. It was found that in addition to glibenclamide and tolbutamide also g liclazide (1 mM) and tolazamide (1 mM) block contractions induced by p rostaglandin F-2 alpha and the thromboxane A(2) mimetic U-46619 in rat aorta, but not the contractions elicited by norepinephrine, serotonin or high potassium. Glibenclamide (10 mu M) inhibits the prostaglandin F-2 alpha- and U-46619-induced contractions on rat tail, femoral and renal interlobar arteries and on bovine retinal and ciliary arteries, but not those on aorta and carotid artery from guinea pigs and on huma n subcutaneous arteries. Glibenclamide (10 mu M), tolbutamide (1 mM), tolazamide (1 mM) and gliclazide (1 mM) all block contractions induced by U-46619, but not those induced by carbachol, on rat intrapulmonary bronchioles. However, prostanoid-induced contractions of guinea-pig t rachea and main bronchi are not influenced by glibenclamide (10 mu M). From these results it is concluded that the ability of sulfonylureas to block prostanoid-induced contractions is shared by all sulfonylurea s tested, that this is not limited to vascular smooth muscle cells and that it shows a heterogeneity, that might be linked to interspecies d ifferences. (C) 1997 Elsevier Science B.V.