Facial blood flow, which typically exhibits distinctive oscillation at a frequency of around 0.1 Hz, has been extensively studied. Although this oscillation may include important information about blood flow regulation, its origin remains unknown. The spatial phase distribution of the oscillation is thus desirable. Therefore, we visualized facial blood volume oscillation at a frequency of around 0.1 Hz using a digital camera imaging method with an improved approximation equation, which enabled precise analysis over a large area. We observed a slow spatial movement of the 0.1-Hz oscillation. The oscillation phase was not synchronized, but instead moved slowly. The phase velocity varies with person, measurement location, and time. An average phase velocity of 3.8 mm/s was obtained for several subjects. The results are consistent with previous studies; however, the conventional explanation that the blood flow at a certain point oscillates independently of adjacent areas should be corrected. If the primary origin of the movement is myogenic activity, the movement may ascend along a blood vessel toward the upstream. Sevabertinib concentration Otherwise, the oscillation and its propagation can be considered to be related to Mayer waves. By determining the mechanism, some questions regarding Mayer waves can be answered. The direction of the wave (upstream or downstream) provides important information.Cytochrome P450 (CYP-450) metabolites of arachidonic acid epoxyeicosatrienoic acids (EETs) and 20-hydroxyeicosatetraenoic acid (20-HETE) have established role in regulation of blood pressure (BP) and kidney function. EETs deficiency and increased renal formation of 20-HETE contribute to hypertension in spontaneously hypertensive rats (SHR). We explored the effects of 14,15-EET analog (EET-A) and of 20-HETE receptor blocker (AAA) on BP and kidney function in this model. In anesthetized SHR the responses were determined of mean arterial blood pressure (MABP), total renal (RBF), and cortical (CBF) and inner-medullary blood flows, glomerular filtration rate and renal excretion, to EET-A, 5 mg/kg, infused i.v. for 1 h to rats untreated or after blockade of endogenous EETs degradation with an inhibitor (c-AUCB) of soluble epoxide hydrolase. Also examined were the responses to AAA (10 mg/kg/h), given alone or together with EET-A. EET-A significantly increased RBF and CBF (+30% and 26%, respectively), seen already within first 30 min of infusion. The greatest increases in RBF and CBF (by about 40%) were seen after AAA, similar when given alone or combined with EET-A. MABP decreased after EET-A or AAA but not significantly after the combination thereof. In all groups, RBF, and CBF increases preceded the decrease in MABP. We found that in SHR both EET-A and AAA induced renal vasodilation but, unexpectedly, no additive effect was seen. We suggest that both agents have a definite therapeutic potential and deserve further experimental and clinical testing aimed at introduction of novel antihypertensive therapy.

Clinical experience showed that the majority of Torsade de Pointes (TdP) ventricular tachyarrhythmia (VT) in patients with long QT syndrome (LQTS) are self-terminating (ST), but the few that are non-self-terminating (NST) are potentially fatal. A paramount issue in clinical arrhythmology is to understand the electrophysiological mechanism of ST vs. NST TdP VT.

We investigated the electrophysiological mechanism of ST vs. NST TdP VT in the guinea pig Anthopleurin-A experimental model of LQTS, a close surrogate model of congenital LQT3. We utilized simultaneous optical recordings of membrane voltage (V

) and intracellular calcium (Ca

) and a robust analytical method based on spatiotemporal entropy difference (E

) to investigate the hypothesis that early V

/Ca

uncoupling during TdP VT can play a primary role in perpetuation of VT episodes.

We analyzed a total of 35 episodes of TdP VT from 14 guinea pig surrogate models of LQTS, including 23 ST and 12 NST VTs. E

values for NST VT were significantly higher than E

values for ST VT. Analysis of wave front topology during the early phase of ST VT showed the Ca

wave front following closely V

wave front consistent with a lower degree of E

. In contrast, NST VT was associated with uncoupling of V

/Ca

wave fronts during the first 2 or 3 cycles of VT associated with early wave break propagation pattern.

Utilizing a robust analytical method we showed that, in comparison to ST TdP VT, NST VT was consistently predated by early uncoupling of V

/Ca

that destabilized wave front propagation and can explain a sustained complex reentrant excitation pattern.

Utilizing a robust analytical method we showed that, in comparison to ST TdP VT, NST VT was consistently predated by early uncoupling of V m /Ca i that destabilized wave front propagation and can explain a sustained complex reentrant excitation pattern.Adenosine (ADO) involvement in lung injury depends on the activation of its receptors. The ADO A2A receptor (ADORA2A) and A2B receptor (ADORA2B) are best described to have both tissue-protective and tissue-destructive processes. However, no approach has been effective in delineating the mechanism(s) involved with ADO shifting from its tissue-protective to tissue-destructive properties in chronic airway injury. Using cigarette smoke (CS) as our model of injury, we chronically exposed Nuli-1 cells to 5% CS extract (CSE) for 3 years establishing a long-term CSE exposure model (LTC). We found significant morphological changes, decreased proliferation, and migration resulting in impaired airway wound closure in LTC. Further investigations showed that long-term CSE exposure upregulates CD73 and ADORA2B expression, increases ADO production, inhibits PKC alpha activity and p-ERK signaling pathway. Knocking down ADORA2B and/or CD73 in LTC activates PKC alpha and increases p-ERK signaling. Knocking down both showed better improvement in wound repair than either alone. In vivo experiments also showed that double knockout CD73 and ADORA2B remarkably improved CS-induced lung injury by activating PKC alpha, reducing the inflammatory cell number in bronchoalveolar lavage fluid and the production of inflammatory mediator IL-6, inhibiting the fibrosis-like lesions and decreasing collagen deposition surrounding bronchioles. Collectively, long-term CSE exposure upregulates CD73 expression and increases ADO production, which promotes low affinity ADORA2B activation and subsequent diminution of PKC alpha activity and ERK signaling pathway, and inhibition of airway wound repair. Moreover, the data suggesting ADORA2B and CD73 as potential therapeutic targets may be more efficacious in improving chronic CS lung diseases and impaired wound repair.