Vascular Responses in Male and Female Hypertensive Rats With Hyperhomocysteinemia

We studied vascular responses in spontaneously hypertensive rats (SHR) of both genders after methionine (Met) loading to test whether or not there were gender differences. SHRs were divided into 5 groups: male control (MSHR), female control (FSHR), methionine-loaded (+Met) males (MSHR[+Met]) and females (FSHR[+Met]), and male SHR with both 17β-estradiol (E 2 ) and Met administration (MSHR[+E 2 +Met]). Treated groups received Met (1g/kg body weight per day) in water for 6 weeks. Systolic blood pressure (SBP) was monitored weekly. Aortic contractile (phenylephrine-induced) and relaxant (acetylcholine-induced as endothelium-dependent relaxation, or EDR) responses as well as endothelial suppression (with nitric oxide synthase inhibitor) were evaluated at the end of experiments. Serum homocysteine (Hcy) level was also determined. Met overloading caused a nearly 3-fold increase in serum Hcy in each gender (moderate hyperhomocysteinemia, or HHcy). As age increased, SBP increased in all groups; FSHR(+Met) had the least elevation and significantly less increase of SBP than FSHR at the end of 6 weeks. There was also a significant increase of EDR in FSHR(+Met) compared with both FSHR and MSHR(+Met). FSHR(+Met) had the highest level of endothelium suppression. Furthermore, EDR in MSHR(+E 2 +Met) was significantly higher than that in MSHR(+Met). Direct Hcy feeding appeared to reduce the development of hypertension in female SHR in 3 weeks. Hence, SBP development was partially alleviated, whereas EDR and endothelium suppression were enhanced in female SHR with HHcy. E 2 could mimic the gender-dependent effect of HHcy on EDR enhancement in MSHR; moreover, reduction of SBP development occurred in Hcy-fed FSHR.