Simultaneously Increased TxA2 Activity in Isolated Arterioles and Platelets of Rats With Hyperhomocysteinemia

Abstract—We aimed to elucidate the effect of hyperhomocysteinemia (HHcy) on the synthesis of prostaglandins in rat skeletal muscle arterioles and platelets. Male Wistar rats were divided into 2 groups: (1) control rats, with plasma Hcy levels of 6.5±0.5 μmol/L (n=50) and (2) rats with HHcy, induced by daily intake of 1 g/kg body weight methionine in the drinking water for 4 weeks (plasma Hcy levels were 20.6±3.0 μmol/L, P<0.01 versus controls; n=50). Arterioles (diameter ≈130 μm) were isolated from the gracilis muscle, cannulated, and pressurized (at 80 mm Hg), and changes in their diameters were followed by video microscopy. Constrictions to bradykinin (BK; 10−10 to 10−7 mol/L) were significantly greater in HHcy than in control rat arterioles (at 10−9 mol/L BK, changes were 11±3% in control and 41±9% in HHcy rats). The cyclooxygenase inhibitor indomethacin (10−5 mol/L), the prostaglandin H2/thromboxane A2 (PGH2/TxA2) receptor antagonist SQ 29,548 (10−6 mol/L), or the TxA2 synthase inhibitor furegrelate (...