The diminished extracellular matrix production induced by isradipine, a calcium channel blocker, is completely abolished by cyclooxygenase inhibition.
Collagen and glycosaminoglycan synthesis are well known to be enhanced during early atherogenesis. In this experimental study the synthesis of collagen was determined using 14C proline incorporation, the glycosaminoglycan production by means of 35S-sulphate incorporation and subsequent quantification by means of autoradiography. Isradipine, a new calcium channel blocker of the dihydropyridine family at a dose of 0.3 mg/kg significantly (p less than 0.01) decreased the incorporation of both the radioactive precursors. This effect was abolished by a concomitant aspirin treatment, while aspirin alone did not exert any significant effect on the precursor incorporation. These data suggest that isradipine, which is known to stimulate PGI2 synthesis, may exert this antiatherosclerotic inhibitory action on extracellular matrix production via the endogenous liberation of PGI2.
Fitscha
P
P
2nd Department of Internal Medicine, Policlinic Vienna, Austria.
Keiler
A
A
Rauscha
F
F
O'Grady
J
J
Sinzinger
H
H
D000818:Animals; D001161:Arteriosclerosis / Q000517:prevention & control; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003094:Collagen / Q000096:biosynthesis; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004095:Dihydropyridines / Q000008:administration & dosage / Q000494:pharmacology*; D004347:Drug Interactions; D011464:Epoprostenol / Q000096:biosynthesis; D005109:Extracellular Matrix / Q000187:drug effects* / Q000378:metabolism; D006025:Glycosaminoglycans / Q000096:biosynthesis; D017275:Isradipine; D008297:Male; D011817:Rabbits
D002121:Calcium Channel Blockers; D016861:Cyclooxygenase Inhibitors; D004095:Dihydropyridines; D006025:Glycosaminoglycans; D003094:Collagen; D011464:Epoprostenol; D001241:Aspirin; D017275:Isradipine