Cardiac reactive hyperemia is impaired in a rat model of hyperhomocysteinemia (HHcy)

Abstract

The endothelium‐mediated vasomotor function of skeletal muscle arterioles has been shown to be impaired in HHcy. Thus we hypothesized that HHcy modulates the reactive hyperemic response of coronary circulation following occlusion. Rats received 1g/kg of body weight methionine daily, for 5 weeks in the drinking water to induce mild HHcy (~ 30 μmol vs. ~ 7 μmol). In Langendorff‐perfused hearts reactive hyperemia (RH) after 5 min of global ischemia was studied prior to and after the simultaneous administration of the nitric oxide synthase inhibitor L‐NAME (10−4M) and the cyclooxygenase inhibitor indomethacin (INDO 10−5M) into the perfusate. We have found that the early peak values of reactive hyperemia were not significantly different in HHcy and control (C) groups (at 2 min of RH: HHcy: 139±14 vs. C: 147±19% of basal flow). The later phase of reactive hyperemia however, was significantly diminished in HHcy hearts (at 8 min of RH: HHcy: 116±7 vs. C: 130±14% of basal flow). Presence of L‐NAME+INDO eliminated the difference between the reactive hyperemia of control and HHcy hearts. On the basis of these findings we propose that cardiac reactive hyperemia is impaired in HHcy, primarily due to reduced release of endothelium‐derived dilator factors. (Grants: Hungarian Sci. Res. Funds/OTKA T48376, 61694, 68502, T67984; and Am. Heart Assoc. NE Aff. 0555897T, USA).