Ca2+/calmodulin-dependent protein kinase kinase β phosphorylation of Sirtuin 1 in endothelium is atheroprotective.

Atheroprotective flow exerts antioxidative and anti-inflammatory effects on vascular endothelial cells (ECs), in part through the induction of Sirtuin 1 (SIRT1), a class III histone deacetylase. The role of Ca(2+)/calmodulin-dependent protein kinase kinase (CaMKK)β in flow induction of SIRT1 both in vitro and in vivo was investigated. Pulsatile shear stress mimicking atheroprotective flow increased the level of SIRT1 in cultured ECs by enhancing its stability, and this effect was abolished by inhibition or knockdown of CaMKKβ.

Flow-Dependent Regulation of Kruppel-Like Factor 2 Is Mediated by MicroRNA-92a.

Background: Upregulated by atheroprotective flow, the transcription factor Krüppel-like factor 2 (KLF2) is crucial for maintaining endothelial function. MicroRNAs (miRNAs) are noncoding small RNAs that regulate gene expression at the posttranscriptional level. We examined the role of miRNAs, particularly miR-92a, in the atheroprotective flow-regulated KLF2.

Effect of estrogen on cerebrovascular prostaglandins is amplified in mice with dysfunctional NOS.

Chronic estrogen treatment increases endothelial vasodilator function in cerebral arteries. Endothelial nitric oxide (NO) synthase (eNOS) is a primary target of the hormone, but other endothelial factors may be modulated as well. In light of possible interactions between NO and prostaglandins, we tested the hypothesis that estrogen treatment increases prostanoid-mediated dilation using NOS-deficient female mouse models, i.

Development affects in vitro vascular tone and calcium sensitivity in ovine cerebral arteries.

We have shown recently that development from neonatal to adult life affects cerebrovascular tone of mouse cerebral arteries through endothelium-derived vasodilatory mechanisms. The current study tested the hypothesis that development from fetal to adult life affects cerebral artery vascular smooth muscle (VSM) [Ca(2+)](i) sensitivity and tone through a mechanism partially dependent upon endothelium-dependent signalling. In pressurized resistance sized cerebral arteries ( approximately 150 microm) from preterm (95 +/- 2 days gestation (95 d)) and near-term (140 +/- 2 days gestation (140 d)) fetuses, and non-pregnant adults, we measured vascular diameter (microm) and [Ca(2+)](i) (nm) as a function of intravascular pressure.

Selected contribution: Effects of aging on cerebrovascular tone and [Ca2+]i.

The lower limits of cerebral blood flow autoregulation shift toward high pressures in aged compared with young rats. Intraluminal pressure stimulates contractile mechanisms in cerebral arteries that might, in part, cause an age-dependent shift in autoregulation. The present project tested two hypotheses.

Maturation depresses mouse cerebrovascular tone through endothelium-dependent mechanisms.

In light of previous observations that the range of arterial pressures over which cerebral blood flow is autoregulated differs dramatically in neonates and adults, the present experiments explored the hypothesis that pressure-induced intrinsic arterial tone is regulated differently in neonatal and adult cerebral arteries. In cannulated and pressurized endothelium-intact mouse cerebral arteries <150 microm in diameter, active intrinsic tone was evident at intraluminal pressures as low as 10 mmHg in neonatal arteries, but only at pressures of 60 mmHg or greater in adult arteries. Administration of 10 microM indomethacin produced no significant effect on tone at any pressure in either neonatal or adult arteries, but subsequent addition of 100 microroarginine methyl ester (NAME) significantly vasoconstricted both neonatal and adult arteries at all pressures.

Male-female differences in the relative contribution of endothelial vasodilators released by rat tail artery.

Several different vasodilator substances can be released by vascular endothelium in response to mechanical stimuli and vasoactive agents. The purpose of this study was to determine whether there is a male-female difference in the relative contributions of nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) to endothelium-dependent vasodilation. Perfusion pressure was measured in isolated tail arteries from male and female rats.