Treatment with the ALK5 inhibitor SB-525334 prevented high salt intake-induced increases in blood pressure and normalized endothelial function in rats.
Does SB-525334 prevent high salt-induced endothelial dysfunction and blood pressure increases in Sprague-Dawley rats?
Inhibition of TGF-β signaling prevents high salt-induced endothelial dysfunction and blood pressure elevation in rats, suggesting a mechanistic role for TGF-β in salt-sensitive hypertension.
Endothelial dysfunction has been shown to be predictive of subsequent cardiovascular events and death. Through a mechanism that is incompletely understood, increased dietary salt intake promotes endothelial dysfunction in healthy, salt-resistant humans. The present study tested the hypothesis that dietary salt-induced transforming growth factor (TGF)-β promoted endothelial dysfunction and salt-dependent changes in blood pressure (BP). Sprague-Dawley rats that received diets containing 0.3% NaCl low salt (LS) or 8.0% NaCl high salt (HS) were treated with vehicle or SB-525334, a specific inhibitor of TGF-β receptor I/activin receptor-like kinase 5, beginning on day 5. BP was monitored using radiotelemetry in four groups of rats (LS, LS + SB-525334, HS, and HS + SB-525334) for up to 14 days. By day 14 of the study, mean daytime systolic BP and mean pulse pressure of the HS group treated with vehicle was greater than those in the other three groups; mean daytime systolic BP and pulse pressure of the HS + SB-525334 group did not differ from the LS and LS + SB-525334-treated groups. Whereas mean systolic BP, mean diastolic BP, and mean arterial pressure did not differ among the groups on the seventh day of the study, endothelium-dependent vasorelaxation was impaired specifically in the HS group; treatment with the activin receptor-like kinase 5 inhibitor prevented the dietary HS intake-induced increases in phospho-Smad2 (Ser(465/467)) and NADPH oxidase-4 in endothelial lysates and normalized endothelial function. These findings suggest that HS-induced endothelial dysfunction and the development of salt-dependent increases in BP were related to endothelial TGF-β signaling.
Feng et al. (Thu,) conducted a other in Endothelial dysfunction and salt-dependent blood pressure changes. SB-525334 vs. Vehicle was evaluated on Blood pressure and endothelium-dependent vasorelaxation. Treatment with the ALK5 inhibitor SB-525334 prevented high salt intake-induced increases in blood pressure and normalized endothelial function in rats.