The vascular Na,K-ATPase: clinical implications in stroke, migraine, and hypertension.

In the vascular wall, the Na,K-ATPase plays an important role in the control of arterial tone. Through cSrc signaling, it contributes to the modulation of Ca2+ sensitivity in vascular smooth muscle cells. This review focuses on the potential implication of Na,K-ATPase-dependent intracellular signaling pathways in severe vascular disorders; ischemic stroke, familial migraine, and arterial hypertension.

Colchicine enhances β adrenoceptor-mediated vasodilation in men with essential hypertension.

Aims: The aim of this study is to examine whether colchicine improves β adrenoceptor-mediated vasodilation in humans by conducting a double-blinded, placebo-controlled intervention study. Colchicine treatment has known beneficial effects on cardiovascular health and reduces the incidence of cardiovascular disease. Studies in isolated rodent arteries have shown that colchicine can enhance β adrenoceptor-mediated vasodilation, but this has not been determined in humans.

Vasomotion in Retinal Arterioles Is Modified by Exercise and Flicker Stimulation.

Purpose: Vasomotion is spontaneous oscillations in the diameter of resistance vessels with derived effects on blood flow, and it has been proposed that disturbances in vasomotion may be involved in retinal vascular disease. The purpose of this study was to investigate whether retinal vasomotion shows regional variation and is modified by activated autoregulation.

Methods: Video recordings of the diameter of retinal arterioles previously obtained from 55 normal persons were subjected to Fourier analysis to characterize the frequencies and propagation of spontaneous diameter changes in retinal arterioles.

The microtubule network enables Src kinase interaction with the Na,K-ATPase to generate Ca flashes in smooth muscle cells.

Several local Ca events are characterized in smooth muscle cells. We have previously shown that an inhibitor of the Na,K-ATPase, ouabain induces spatially restricted intracellular Ca transients near the plasma membrane, and suggested the importance of this signaling for regulation of intercellular coupling and smooth muscle cell contraction. The mechanism behind these Na,K-ATPase-dependent "Ca flashes" remains to be elucidated.

Dynein Coordinates β2-Adrenoceptor-Mediated Relaxation in Normotensive and Hypertensive Rat Mesenteric Arteries.

Background: The voltage-gated potassium channel (Kv)7.4 and Kv7.5 channels contribute to the β-adrenoceptor-mediated vasodilatation.

The cardiovascular challenges in giraffes.

Giraffes are the highest living animals on Earth and therefore are challenged by gravity more than any other species. In particular the cardiovascular system needs to adapt to this challenge. Giraffes have a mean blood pressure around 200 mmHg, which ensures a mean arterial pressure near the head of 100 mmHg when the giraffe is standing with the neck in a near vertical position.

Migraine-Associated Mutation in the Na,K-ATPase Leads to Disturbances in Cardiac Metabolism and Reduced Cardiac Function.

Background Mutations in gene encoding the Na,K-ATPase α isoform are associated with familial hemiplegic migraine type 2. Migraine with aura is a known risk factor for heart disease. The Na,K-ATPase is important for cardiac function, but its role for heart disease remains unknown.

Identification of novel proteins and mechanistic pathways associated with early-onset hypertension by deep proteomic mapping of resistance arteries.

Resistance arteries are small blood vessels that create resistance to blood flow. In hypertension, resistance arteries undergo remodeling, affecting their ability to contract and relax appropriately. To date, no study has mapped the hypertension-related proteomic changes in resistance arteries.

ATP induced calcium signaling activity in perivascular cells differ at different vascular branch levels in the porcine retina.

Background: The purine adenosine triphosphate (ATP) plays a significant role in retinal blood flow regulation and recent evidence suggests that the vasoactive effect of the compound differs in vessels at different branching level. However, the cellular basis for the regulation of retinal blood flow mediated by ATP has only been scarcely studied.

Methods: Perfused porcine hemiretinas (n = 60) were loaded with the calcium-sensitive fluorophore Oregon Green ex vivo.

Did giraffe cardiovascular evolution solve the problem of heart failure with preserved ejection fraction?

The evolved adaptations of other species can be a source of insight for novel biomedical innovation. Limitations of traditional animal models for the study of some pathologies are fueling efforts to find new approaches to biomedical investigation. One emerging approach recognizes the evolved adaptations in other species as possible solutions to human pathology.

Dynein regulates Kv7.4 channel trafficking from the cell membrane.

The dynein motor protein transports proteins away from the cell membrane along the microtubule network. Recently, we found the microtubule network was important for regulating the membrane abundance of voltage-gated Kv7.4 potassium channels in vascular smooth muscle.

Brain capillary pericytes and neurovascular coupling.

The neurovascular coupling ensures that cerebral activity is matched by the relevant blood flow. The control of the blood flow is mediated by capillaries and by the precapillary aterioles. It is the tone of the mural cells, which include pericytes, smooth muscle cells and cells with intermediate phenotypes between pericytes and smooth muscle cells, that determine the the diameter of the blood vessels and consequently the flow.

Sodium bicarbonate cotransporter NBCn1/Slc4a7 affects locomotor activity and hearing in mice.

Despite a widespread expression pattern in the central nervous system, the role of the sodium bicarbonate cotransporter NBCn1/Slc4a7 has not been investigated for locomotor activity, emotion and cognition. Here, we addressed the behavioral consequences of NBCn1 knockout and evaluated hearing and vision that are reportedly impaired in an earlier line of NBCn1 knockout mice and may contribute to behavioral changes. In a circular open field, the knockout mice traveled a shorter distance, especially in the periphery of the chamber, than wildtype littermates.

Sympathetic and Sensory-Motor Nerves in Peripheral Small Arteries.

Small arteries, which play important roles in controlling blood flow, blood pressure, and capillary pressure, are under nervous influence. Their innervation is predominantly sympathetic and sensory motor in nature, and while some arteries are densely innervated, others are only sparsely so. Innervation of small arteries is a key mechanism in regulating vascular resistance.

A paradoxical increase of force development in saphenous and tail arteries from heterozygous ANO1 knockout mice.

A Ca -activated Cl channel protein, ANO1, is expressed in vascular smooth muscle cells where Cl current is thought to potentiate contraction by contributing to membrane depolarization. However, there is an inconsistency between previous knockout and knockdown studies on ANO1's role in small arteries. In this study, we assessed cardiovascular function of heterozygous mice with global deletion of exon 7 in the ANO1 gene.

The Remarkable Cardiovascular System of Giraffes.

Gravity affects the physiology of many animals, and the effect is, for good reason, most pronounced in tall species. The physiology-in particular, cardiovascular function-of giraffes has therefore captivated the interest of physiologists for centuries. Several studies document high mean arterial blood pressure of giraffes of about 200 mm Hg.

Differential Effects of Intra- and Extravascular ATP on the Diameter of Porcine Vessels at Different Branching Levels Ex Vivo.

Purpose: Adenosine triphosphate (ATP) is involved in the diameter regulation of retinal vessels. The compound has been shown to induce both constriction and dilatation, but the detailed mechanisms underlying these effects and the site of action of the compound are not known in detail. Therefore, the purpose of the present study was to investigate whether the vasoactive effects of ATP on retinal vessels depend on intra- and extravascular application, and to study whether the effects differ at different vascular branching levels.

Increased Alcohol Consumption in Mice Lacking Sodium Bicarbonate Transporter NBCn1.

The previous reports on an addiction vulnerability marker in the human SLC4A7 gene encoding the Na/HCO transporter NBCn1 suggest that this pH-regulating protein may affect alcohol-related behavior and response. Here, we examined alcohol consumption and sensitivity to the sedative effects of alcohol in male NBCn1 knockout mice. These mice displayed lower pH in neurons than wildtype controls, determined by intracellular pH in hippocampal neuronal cultures.

A sex-specific, COX-derived/thromboxane receptor activator causes depolarization and vasoconstriction in male mice mesenteric resistance arteries.

We investigated whether sex differences exist in cyclooxygenase-dependent effects on membrane potential and relaxation in mice mesenteric resistance arteries. Mesenteric small arteries of 9- to 12-week-old, male and female, wild-type mice, db/+ mice and diabetic db/db mice were mounted in myographs for measurements of isobaric diameter and smooth muscle cell membrane potential. Acetylcholine caused smaller dilation of arteries from male db/+ mice compared to arteries from female db/+ mice.

Abnormal neurovascular coupling as a cause of excess cerebral vasodilation in familial migraine.

Aims: Acute migraine attack in familial hemiplegic migraine type 2 (FHM2) patients is characterized by sequential hypo- and hyperperfusion. FHM2 is associated with mutations in the Na, K-ATPase α2 isoform. Heterozygous mice bearing one of these mutations (α2+/G301R mice) were shown to have elevated cerebrovascular tone and, thus, hypoperfusion that might lead to elevated concentrations of local metabolites.