Dysfunction of blood pressure regulation in hyperhomocyteinemia model in rats.

Hyperhomocysteinemia (HHC) has been reported to be one of risk factors for cardiovascular disease. We investigated the effects of HHC on blood pressure regulation and its association with damage to the thoracic aorta and imbalance of redox in plasma in rats. Rats were fed a methionine enriched diet (Met diet) or a methionine and cholesterol (Met+Chol diet) enriched diet for 16 weeks to create a subchronic HHC model, in which the plasma concentration of homocysteine was about 7 times higher than that of control rats. The increase in systolic blood pressure (Δ-SBP) from sympathetic stimulation by L-epinephrine was 2- to 3-fold larger in HHC model in rats than that in control rats after several weeks of the treatment. These findings suggest that HHC deteriorates vaso-regulatory function, which could bring on an increased risk of cardiovascular events in humans. In addition, some of the elastic lamellae in the aorta were disrupted in the HHC group. However, the content of cross-linkages which give elasticity and mechanical strength in the lamellae, was not significantly different between HHC and control rats. Also plasma concentrations of thiobarbituric acid reactive substance and glutathione as indicators for redox balance in plasma were not different. In conclusion, the deterioration of vaso-regulation in HHC model in rats might be caused by the damage to elastic lamellae in the aorta, and not by oxidative stresses.