Key result
Combination therapy with olmesartan and azelnidipine significantly improved severely impaired EDHF-mediated responses in diabetic ApoE-/- mice, likely via activation of the endothelial Akt-eNOS pathway.
Why the study?
Does combination therapy with olmesartan and azelnidipine improve EDHF-mediated responses in diabetic ApoE(-/-) mice?
Does combination therapy with olmesartan and azelnidipine improve EDHF-mediated responses in diabetic ApoE(-/-) mice?
Combination therapy with olmesartan and azelnidipine improves severely impaired EDHF-mediated responses in diabetic ApoE(-/-) mice, likely via activation of the endothelial Akt-eNOS pathway.
Hypothesis-generating for endothelial protection with ARB-CCB combinations in diabetes; should not change clinical practice.
BACKGROUND: The endothelium modulates vascular tone by synthesizing and releasing several vasodilating factors, including vasodilator prostaglandins, nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF). In the present study, we examined whether an angiotensin-receptor blocker, a calcium-channel blocker or their combination improved EDHF-mediated responses in diabetic apolipoprotein E-deficient (ApoE(-/-)) mice. METHODS AND RESULTS: We used male C57BL/6N (control) and streptozocin-induced diabetic ApoE(-/-) mice. The diabetic ApoE(-/-) mice were administered oral vehicle (untreated), olmesartan (OLM, 30 mgxkg(-1)xday(-1)), azelnidipine (AZL, 10 mgxkg(-1)xday(-1)), their combination (OLM + AZL), or hydralazine (HYD 5 mgxkg(-1)xday(-1)) for 5 weeks. In the untreated group, systolic blood pressure was significantly higher and both EDHF-mediated relaxation and endothelium-dependent hyperpolarization were markedly reduced as compared with the control group. Although EDHF-mediated relaxation was not significantly improved in the HYD, OLM and AZL groups, it was significantly improved in the OLM + AZL group, as was also the case with phosphorylation of Akt and endothelial NO synthase (eNOS). In contrast, the endothelium-independent relaxation response to sodium nitroprusside or NS-1619 (a direct opener of K(Ca) channels) was unaltered in any group. CONCLUSIONS: OLM + AZL may improve the severely impaired EDHF-mediated responses in diabetic ApoE(-/-) mice, in which activation of the endothelial Akt - eNOS pathway may be involved.
No takes yet. Share an insight, caveat, or question.
Hosoya et al. (2010) studied Diabetes and hypercholesterolemia (Endothelial dysfunction) (n=36). Olmesartan and Azelnidipine combination vs. Vehicle (untreated), Olmesartan alone, Azelnidipine alone, Hydralazine, and non-diabetic controls was evaluated on EDHF-mediated relaxation and endothelium-dependent hyperpolarization (p=<0.05). Combination therapy with olmesartan and azelnidipine significantly improved severely impaired EDHF-mediated responses in diabetic ApoE-/- mice, likely via activation of the endothelial Akt-eNOS pathway.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: