Preservation of EDHF‐dependent vasodilation and connexin expression in hyperhomocysteinemic mice

Hyperhomocysteinemia (HHcy) impairs endothelium‐dependent vasodilation by reducing NO· bioavailability, and possibly endothelial‐derived hyperpolarizing factor (EDHF). We tested the hypothesis that HHcy impairs EDHF by altering gap junction gene expression (Cx37, Cx40, Cx43). HHcy was induced in male C57BL/6 mice, with a 6‐wk high methionine/low‐B vitamin diet (serum Hcy: 91.9 ± 48.8 μM), and compared to age‐matched controls (6.3 ± 1.7 μM). Dilation to acetylcholine (10 −9 –10 −4 M) was measured in isolated, cannulated, pressurized (75 mmHg) mesenteric arteries with and without L‐NAME (10 −4 M) and indomethacin (10 −5 M) to test endothelium‐dependent and EDHF‐dependent dilation, respectively. Dilation was attenuated (p<0.05) in HHcy arteries, however EDHF‐dependent dilation was not different. Relative mRNA expression of Cx37, Cx40, Cx43, and eNOS, measured in the mesenteric artery, aorta, and cremaster muscle by real‐time PCR, was similar, except for greater Cx37 in mesenteric artery and Cx43 in aorta of HHcy mice (p<0.05). Western‐blotting for Cx43, eNOS, and phospho‐S1179‐eNOS in aorta and mesenteric arteries, indicated less eNOS and phospho‐S1179‐eNOS/eNOS in HHcy mesenteric arteries (p<0.05). In conclusion, EDHF‐dependent dilation and connexin expression is preserved in chronic HHcy mice, and reduced eNOS may underlie the impaired vasodilation. Supported by Jeffress Trust and HHMI‐UBSEP.