Perivascular adipose tissue-derived adiponectin activates BK(Ca) channels to induce anticontractile responses.

This study aims to identify the potential mechanisms by which perivascular adipose tissue (PVAT) reduces tone in small arteries. Small mesenteric arteries from wild-type and large-conductance Ca(2+)-activated K(+) (BKCa) channel knockout mice were mounted on a wire myograph in the presence and absence of PVAT, and contractile responses to norepinephrine were assessed. Electrophysiology studies were performed in isolated vessels to measure changes in membrane potential produced by adiponectin.

Endothelium-derived hyperpolarising factors and associated pathways: a synopsis.

The term endothelium-derived hyperpolarising factor (EDHF) was introduced in 1987 to describe the hypothetical factor responsible for myocyte hyperpolarisations not associated with nitric oxide (EDRF) or prostacyclin. Two broad categories of EDHF response exist. The classical EDHF pathway is blocked by apamin plus TRAM-34 but not by apamin plus iberiotoxin and is associated with endothelial cell hyperpolarisation.

Targeted deletion of the extracellular signal-regulated protein kinase 5 attenuates hypertrophic response and promotes pressure overload-induced apoptosis in the heart.

Rationale: Mitogen-activated protein kinase (MAPK) pathways provide a critical connection between extrinsic and intrinsic signals to cardiac hypertrophy. Extracellular signal-regulated protein kinase (ERK)5, an atypical MAPK is activated in the heart by pressure overload. However, the role of ERK5 plays in regulating hypertrophic growth and hypertrophy-induced apoptosis is not completely understood.

Cardiac-specific deletion of mkk4 reveals its role in pathological hypertrophic remodeling but not in physiological cardiac growth.

Mitogen-activated protein kinase kinase (MKK)4 is a critical member of the mitogen-activated protein kinase family. It is able to activate the c-Jun NH(2)-terminal protein kinase (JNK) and p38 mitogen-activated protein kinase in response to environmental stresses. JNK and p38 are strongly implicated in pathological cardiac hypertrophy and heart failure; however, the regulatory mechanism whereby the upstream kinase MKK4 activates these signaling cascades in the heart is unknown.

Evidence for the presence of GPRC6A receptors in rat mesenteric arteries.

In this study, the presence of GPRC6A receptors in rat mesenteric artery was investigated. In artery homogenates, GPRC6A mRNA was detected and Western blotting showed the presence of GPRC6A protein. Immunohistochemical studies revealed GPRC6A in both endothelial cells and myocytes.

Impaired small-conductance Ca2+-activated K+ channel-dependent EDHF responses in Type II diabetic ZDF rats.

We have examined the relative contributions of small- and intermediate-conductance Ca(2+)-activated K(+) channels (SK(Ca) and IK(Ca)) to the endothelium-derived hyperpolarizing factor (EDHF) pathway response in small mesenteric arteries of Zucker Diabetic Fatty (ZDF) rats, before and after the development of Type II diabetes, together with Lean controls. Smooth muscle membrane potential was recorded using sharp microelectrodes in the presence of 10 microM indomethacin plus 100 microM N(omega)-nitro-L-arginine. SK(Ca) was selectively inhibited with 100 nM apamin, whereas IK(Ca) was blocked with 10 microM TRAM-39 (2-(2-chlorophenyl)-2,2-diphenylacetonitrile).

Investigation of the role of TASK-2 channels in rat pulmonary arteries; pharmacological and functional studies following RNA interference procedures.

In the present study, we investigated the ability of RNA interference technology to suppress TASK-2 potassium channel expression in human embryonic kidney (HEK293) cells stably transfected with TASK-2 cDNA and in rat isolated intact pulmonary arteries. Lipofectamine-induced transfection of a specific siRNA sequence targeted against TASK-2 resulted in a dose- and time-dependent decrease in TASK-2 channel protein expression. In siRNA-transfected cells the TASK-2 peak currents were significantly smaller than in control cells at every investigated pH, while the pH sensitivity was not altered.

Reduced Ca2+-dependent activation of large-conductance Ca2+-activated K+ channels from arteries of Type 2 diabetic Zucker diabetic fatty rats.

Although it is well established that diabetes impairs endothelium-dependent vasodilation, including those pathways involving vascular myocyte large-conductance Ca(2+)-activated K(+) channels (BK(Ca)), little is known about the effects of diabetes on BK(Ca) activation as an intrinsic response to contractile stimulation. We have investigated this mechanism in a model of Type 2 diabetes, the male Zucker diabetic fatty (ZDF) rat. BK(Ca) function in prediabetic (5-7 wk) and diabetic (17-20 wk) ZDF and lean control animals was assessed in whole arteries using myograph and electrophysiology techniques and in freshly dissociated myocytes by patch clamping.

Evidence in favor of a calcium-sensing receptor in arterial endothelial cells: studies with calindol and Calhex 231.

Small increases in extracellular Ca2+ dilate isolated blood vessels. In the present study, the possibility that a vascular, extracellular Ca2+-sensing receptor (CaSR) could mediate these vasodilator actions was investigated. Novel ligands that interact with the CaSR were used in microelectrode recordings from rat isolated mesenteric and porcine coronary arteries.

Bradykinin-induced, endothelium-dependent responses in porcine coronary arteries: involvement of potassium channel activation and epoxyeicosatrienoic acids.

In coronary arteries, bradykinin opens endothelial intermediate- and small-conductance Ca2+-sensitive K+ channels (IK(Ca) and SK(Ca)) and, additionally, releases epoxyeicosatrienoic acids (EETs) from the endothelium. To clarify the involvement of these pathways in endothelium-dependent myocyte hyperpolarization, bradykinin-induced electrical changes in endothelial cells and myocytes of porcine coronary arteries (following nitric oxide (NO) synthase and cyclooxygenase inhibition) were measured using sharp microelectrodes. Hyperpolarization of endothelial cells by bradykinin (27.

Hydrogen peroxide and endothelium-dependent hyperpolarization in the guinea-pig carotid artery.

This study was designed to determine whether or not endothelium-dependent hyperpolarizations evoked by acetylcholine in the isolated guinea-pig carotid artery involve hydrogen peroxide. Membrane potential was recorded in the vascular smooth muscle cells of that artery. Under control conditions, acetylcholine induced endothelium-dependent hyperpolarization of the vascular smooth muscle cells which was not affected by the presence of catalase, superoxide dismutase or their combination.

Role of SK(Ca) and IK(Ca) in endothelium-dependent hyperpolarizations of the guinea-pig isolated carotid artery.

1. This study was designed to determine whether the endothelium-dependent hyperpolarizations evoked by acetylcholine in guinea-pig carotid artery involve a cytochrome P450 metabolite and whether they are linked to the activation of two distinct populations of endothelial K(Ca) channels, SK(Ca) and IK(Ca.) 2.

Potassium and potassium clouds in endothelium-dependent hyperpolarizations.

A small increase in extracellular K(+) acts as a local, physiological regulator of blood flow to certain vascular beds. The K(+) derives from active tissues such as contracting skeletal muscle and brain and increases blood supply to these organs by the activation of Na(+)/K(+)-ATPases and/or inwardly-rectifying K(+) channels on the vascular myocytes. K(+) liberated from the vascular endothelium also acts as an endothelium-derived hyperpolarizing and relaxing factor within blood vessels.

[Communication between endothelial and smooth muscle cells].

Vascular endothelial cells play a fundamental role in the control of vascular tone, and therefore in the control of local blood flow, by releasing various contracting (endothelin, prostaglandins) and relaxing (prostacycline, NO) factors. An additional mechanism involving the hyperpolarization of the vascular smooth muscle cells is observed mainly in the coronary vascular bed and in the periphery. This phenomenon was attributed to an elusive endothelial factor called endothelium-derived hyperpolarizing factor (EDHF).

Characterization of a charybdotoxin-sensitive intermediate conductance Ca2+-activated K+ channel in porcine coronary endothelium: relevance to EDHF.

1. This study characterizes the K(+) channel(s) underlying charybdotoxin-sensitive hyperpolarization of porcine coronary artery endothelium. 2.

EDHF: bringing the concepts together.

Endothelial cells synthesize and release vasoactive mediators in response to various neurohumoural substances (e.g. bradykinin or acetylcholine) and physical stimuli (e.

Endothelium-dependent hyperpolarization to acetylcholine in carotid artery of guinea pig: role of lipoxygenase.

This study was designed to determine whether lipoxygenase-dependent metabolites of arachidonic acid are involved in the endothelium-dependent hyperpolarization of the guinea pig carotid artery. The membrane potential of vascular smooth muscle cells was measured with intracellular microelectrodes and potassium channels were studied on freshly isolated cells with the patch-clamp technique. Acetylcholine-induced hyperpolarizations were not affected by arachidonyl trifluoromethyl ketone (AACOCF3), quinacrine (phospholipase A inhibitors), or eicosatetraenoic acid (nonspecific inhibitor of lipoxygenase, cytochrome P450, and cyclooxygenase).