Acute intravenous Tempol reduces mean arterial pressure (MAP) and heart rate (HR) in spontaneously hypertensive rats. We investigated the hypothesis that the antihypertensive action depends on generation of hydrogen peroxide, activation of heme oxygenase, glutathione peroxidase or potassium conductances, nitric oxide synthase, and/or the peripheral or central sympathetic nervous systems (SNSs). Tempol caused dose-dependent reductions in MAP and HR (at 174 micromol/kg; DeltaMAP, -57+/- 3 mmHg; and DeltaHR, -50 +/- 4 beats/min). The antihypertensive response was unaffected by the infusion of a pegylated catalase or by the inhibition of catalase with 3-aminotriazole, inhibition of glutathione peroxidase with buthionine sulfoximine, inhibition of heme oxygenase with tin mesoporphyrin, or inhibition of large-conductance Ca(2+)-activated potassium channels with iberiotoxin. However, the antihypertensive response was significantly (P < 0.01) blunted by 48% by the activation of adenosine 5'-triphosphate-sensitive potassium (K(ATP)) channels with cromakalim during maintenance of blood pressure with norepinephrine and by 31% by the blockade of these channels with glibenclamide, by 40% by the blockade of nitric oxide synthase with N(omega)-nitro-L-arginine methyl ester (L-NAME), and by 40% by the blockade of ganglionic autonomic neurotransmission with hexamethonium. L-NAME and hexamethonium were additive, but glibenclamide and hexamethonium were less than additive. The central administration of Tempol was ineffective. The acute antihypertensive action of Tempol depends on the independent effects of potentiation of nitric oxide and inhibition of the peripheral SNS that involves the activation of K(ATP) channels.
Methyl-ammonium lead iodide perovskite (CH3NH3PbI3) has drawn great attention due to its excellent photovoltaic properties. Because of its loosely compacted structure, the structural, electronic and optical properties of CH3NH3PbI3 are sensitive to external modulations. Strain effects on CH3NH3PbI3 are fully investigated by the first principles calculations. The results indicate that the inorganic framework deforms under compression or stretch and the embedded organic CH3NH3+ molecules rotate correspondingly. A band gap oscillation and a new structural phase in response to the external strain were observed for the first time. These phenomena are explained with the nonlinear structural deformation and phase transition under the external strains. The semi-quantitative relationship between the band gap variation and geometry change under the external strain is obtained. We found that the shift of valence band maximum under the external strain is mostly determined by the most stretched or compressed Pb-I bond of CH3NH3PbI3, and the shift of the conduction band minimum under the external strain is likely to be determined by the largest Pb-I-Pb bond angle in the system. These results are important for understanding of strain effects on semiconductors and guiding the experiments to improve the performance of the perovskite solar cells.
Precise patterning with microscale lateral resolution
and widely
tunable heights is critical for integrating colloidal nanocrystals
into advanced optoelectronic and photonic platforms. However, patterning
nanocrystal layers with thickness above 100 nm remains challenging
for both conventional and emerging direct photopatterning methods,
due to limited light penetration depths, complex mechanical and chemical
incompatibilities, and others. Here, we introduce a direct patterning
method based on a thermal mechanism, namely, the thermally activated
ligand chemistry (or TALC) of nanocrystals. The ligand cross-linking
or decomposition reactions readily occur under local thermal stimuli
triggered by near-infrared lasers, affording high-resolution and nondestructive
patterning of various nanocrystals under mild conditions. Patterned
quantum dots fully preserve their structural and photoluminescent
quantum yields. The thermal nature allows for TALC to pattern over
10 μm thick nanocrystal layers in a single step, far beyond
those achievable in other direct patterning techniques, and also supports
the concept of 2.5D patterning. The thermal chemistry-mediated TALC
creates more possibilities in integrating nanocrystal layers in uniform
arrays or complex hierarchical formats for advanced capabilities in
light emission, conversion, and modulation.
The molecular mechanism of tolerance to opiate drugs is poorly understood. We have used single-channel patch-clamp recordings to study opiate receptor effects on dissociated neurons from rat amygdala, a limbic region implicated in addiction processes. A 130-pS inwardly rectifying K ؉ -preferring cation channel was activated by opioid receptors in a membrane-delimited manner. After chronic treatment of the rats with morphine, channel gating changed markedly, with an approximately 100-fold decrease in open probability at a given morphine concentration. The change in channel gating correlated both in time course and in dose of morphine treatment with the development of functional opiate dependence and appeared to arise at a step after G-protein activation and before channel permeation by K ؉ . This decreased receptor-channel coupling appears to be large enough to account quantitatively for opiate tolerance and may represent one of the mechanisms through which tolerance occurs. D rug addiction is a complex process that includes tolerance (the need for increasing drug dosage to achieve the same effect) and dependence (the appearance of adverse effects on drug withdrawal). Human heroin addicts experience tolerance of more than 100-fold if drug availability is unlimited (1). Changes in the number, affinity, or membrane trafficking of opioid receptors (2-6), in the coupling of receptors to Gproteins (7, 8), or in associated second messenger systems (9) have been implicated in opiate tolerance mechanisms; however, these effects are usually on the order of 10 -20% and therefore appear unable to account quantitatively for tolerance. Consequently, the molecular basis of opiate tolerance remains poorly understood.We have used patch-clamp electrophysiology to resolve single ion channels that are activated by opioid receptors and to study changes in channel properties after chronic opiate treatment. We performed these studies by using freshly dissociated neurons from the amygdalohippocampal area (AHA) of 30-to 45-day-old rats. The AHA is an output nucleus of the amygdala (10, 11) and as such is part of a limbic region implicated in the motivational effects of opiates and other drugs of abuse (10-15). AHA neurons are known to display inhibitory responses to opiates in vivo (14). Furthermore, these cells exhibit a decreased inhibition by morphine after chronic treatment, consistent with tolerance, as well as an activation of firing after precipitated withdrawal, consistent with dependence (14). We now describe a K ϩ -permeable channel that is activated by opioid receptors and show that its gating undergoes changes after chronic morphine treatment in a manner that may account for opiate tolerance in limbic neurons.
MethodsCell Preparation. Coronal 300-m sections of the posteriodorsal amygdala were cut on a vibrating tissue slicer under an ice-cold Pipes-buffered solution previously described (16) and were blocked to include the AHA (10) and some underlying amygdaloid nuclei, but excluded the hippocampus. After slowly warming the ...
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