Relation between the amount of smooth muscle of venous tissue and the degree of supersensitivity to isoprenaline caused by inhibition of catechol-O-methyl transferase

Abstract

The relation between the smooth muscle cell mass of dog saphenous vein strips and the degree of supersensitivity to isoprenaline caused by U-0521 (3,4-dihydroxy-2-methyl propiophenone), an inhibitor of the catechol-O-methyl transferase (COMT), was studied. For the quantitative determination of smooth muscle mass, the thickness of the muscle layer as determined by light microscopy and the maximal shortening induced by supramaximal concentration of phenylephrine were used. After the strips had been contracted by 3x10-6M phenylephrine, a concentration which was able to produce an about 90% maximal contraction, dose-response curves to the relaxant effect of isoprenaline were determined in the absence and in the presence of U-0521 (10-4M). It was observed that U-0521 caused marked supersensitivity to the relaxant effect of isoprenaline (varying between 3 and 81 times), as well as an increase of the maximal relaxation caused by this amine (varying between 7 and 120%). The correlation between these data and the smooth muscle cell mass shows that there was a direct proportionality between these parameters. Oxytetracycline (10-4M), an inhibitor of binding of catecholamines to collagen, did not produce any enhancement of the effects of isoprenaline. It is concluded that COMT is related to smooth muscle cells in this tissue.