scholarly journals Smooth Muscle Ion Channels and Regulation of Vascular Tone in Resistance Arteries and Arterioles

2017 ◽  
pp. 485-581 ◽  
Author(s):  
Nathan R. Tykocki ◽  
Erika M. Boerman ◽  
William F. Jackson
Keyword(s):  
Smooth Muscle ◽  
Ion Channels ◽  
Vascular Tone ◽  
Resistance Arteries ◽  
Regulation Of Vascular Tone

scholarly journals Do androgens play a beneficial role in the regulation of vascular tone? Nongenomic vascular effects of testosterone metabolites

2010 ◽  
Vol 298 (5) ◽  
pp. H1301-H1307 ◽  
Author(s):  
Mercedes Perusquía ◽  
John N. Stallone
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Animal Studies ◽  
Vascular Tone ◽  
Resistance Arteries ◽  
Vascular Effects ◽  
Beneficial Effects ◽  
Estrogenic Effects ◽  
Testosterone Metabolites ◽  
Regulation Of Vascular Tone

The marked sexual dimorphism that exists in human cardiovascular diseases has led to the dogmatic concept that testosterone (Tes) has deleterious effects and exacerbates the development of cardiovascular disease in males. While some animal studies suggest that Tes does exert deleterious effects by enhancing vascular tone through acute or chronic mechanisms, accumulating evidence suggests that Tes and other androgens exert beneficial effects by inducing rapid vasorelaxation of vascular smooth muscle through nongenomic mechanisms. While this effect frequently has been observed in large arteries at micromolar concentrations, more recent studies have reported vasorelaxation of smaller resistance arteries at nanomolar (physiological) concentrations. The key mechanism underlying Tes-induced vasorelaxation appears to be the modulation of vascular smooth muscle ion channel function, particularly the inactivation of L-type voltage-operated Ca2+ channels and/or the activation of voltage-operated and Ca2+-activated K+ channels. Studies employing Tes analogs and metabolites reveal that androgen-induced vasodilation is a structurally specific nongenomic effect that is fundamentally different than the genomic effects on reproductive targets. For example, 5α-dihydrotestosterone exhibits potent genomic-androgenic effects but only moderate vasorelaxing activity, whereas its isomer 5β-dihydrotestosterone is devoid of androgenic effects but is a highly efficacious vasodilator. These findings suggest that the dihydro-metabolites of Tes or other androgen analogs devoid of androgenic or estrogenic effects could have useful therapeutic roles in hypertension, erectile dysfunction, prostatic ischemia, or other vascular dysfunctions.

Intracellular mechanisms involved in the regulation of vascular smooth muscle tone

1995 ◽  
Vol 73 (5) ◽  
pp. 565-573 ◽  
Author(s):  
Michael P. Walsh ◽  
Gary J. Kargacin ◽  
John Kendrick-Jones ◽  
Thomas M. Lincoln
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase ◽  
Vascular Smooth Muscle ◽  
Cyclic Gmp ◽  
Vascular Tone ◽  
Light Chains ◽  
Dependent Protein Kinase ◽  
Dependent Protein ◽  
Regulation Of Vascular Tone

Vascular smooth muscle contraction is thought to occur by a mechanism similar to that described for striated muscles, i.e., via a cross-bridge cycling – sliding filament mechanism. This symposium focused on Ca2+ signalling and the role of intracellular free Ca2+ concentration, [Ca2+]i, in regulating vascular tone: how contractile stimuli leading to an increase in [Ca2+]i trigger vasoconstriction and how relaxant signals reduce [Ca2+]i causing vasodilation. M.P. Walsh opened the symposium with an overview emphasizing the central role of myosin phosphorylation–dephosphorylation in the regulation of vascular tone and identifying recent developments concerning regulation of [Ca2+]i, Ca2+ sensitization and desensitization of the contractile response, Ca2+-independent protein kinase C induced contraction, and direct regulation of cross-bridge cycling by the thin filament associated proteins caldesmon and calponin. The remainder of the symposium focused on three specific areas related to the regulation of vascular tone: Ca2+ signalling in relation to smooth muscle structure, structure–function relations of myosin, and the role of cyclic GMP (cGMP) dependent protein kinase. G.J. Kargacin described how smooth muscle cells are structured and how second messenger signals such as Ca2+ might be modified or influenced by this structure. J. Kendrick-Jones then discussed the results of mutagenesis studies aimed at understanding how the myosin light chains, particularly the phosphorylatable (Ca2+–calmodulin dependent) regulatory light chains, control myosin. The vasorelaxant effects of signalling molecules such as β-adrenergic agents and nitrovasodilators are mediated by cyclic nucleotide dependent protein kinases, leading principally to a reduction in [Ca2+]i. T.M. Lincoln described the roles of cyclic nucleotide dependent protein kinases, in particular cyclic GMP dependent protein kinase, in vasodilation.Key words: vascular smooth muscle, regulation of contraction, smooth muscle structure, calcium, cyclic GMP, myosin.

scholarly journals Calcium-Activated Potassium Channels and the Regulation of Vascular Tone

Physiology ◽  
2006 ◽  
Vol 21 (1) ◽  
pp. 69-78 ◽  
Author(s):  
Jonathan Ledoux ◽  
Matthias E. Werner ◽  
Joseph E. Brayden ◽  
Mark T. Nelson
Keyword(s):  
Smooth Muscle ◽  
Potassium Channels ◽  
Vascular Function ◽  
Vascular Tone ◽  
Calcium Signals ◽  
Different Types ◽  
Calcium Activated Potassium Channels ◽  
Regulation Of Vascular Tone

Different calcium signals in the endothelium and smooth muscle target different types of Ca2+-sensitive K+ channels to modulate vascular function. These differential calcium signals and targets represent multilayered opportunities for prevention and/or treatment of vascular dysfunctions.

scholarly journals Role of arachidonic acid lipoxygenase metabolites in the regulation of vascular tone

2009 ◽  
Vol 297 (2) ◽  
pp. H495-H507 ◽  
Author(s):  
Yuttana Chawengsub ◽  
Kathryn M. Gauthier ◽  
William B. Campbell
Keyword(s):  
Arachidonic Acid ◽  
Smooth Muscle ◽  
Vascular Endothelium ◽  
Vascular Tone ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial ◽  
Epoxyeicosatrienoic Acid ◽  
Regulation Of Vascular Tone ◽  
Small Conductance

Stimulation of vascular endothelial cells with agonists such as acetylcholine (ACh) or bradykinin or with shear stress activates phospholipases and releases arachidonic acid (AA). AA is metabolized by cyclooxygenases, cytochrome P-450s, and lipoxygenases (LOs) to vasoactive products. In some arteries, a substantial component of the vasodilator response is dependent on LO metabolites of AA. Nitric oxide (NO)- and prostaglandin (PG)-independent vasodilatory responses to ACh and AA are reduced by inhibitors of LO and by antisense oligonucleotides specifically against 15-LO-1. Vasoactive 15-LO metabolites derived from the vascular endothelium include 15-hydroxy-11,12-epoxyeicosatrienoic acid (15-H-11,12-HEETA) that is hydrolyzed by soluble epoxide hydrolase to 11,12,15-trihydroxyeicosatrienoic acid (11,12,15-THETA). HEETA and THETA are endothelium-derived hyperpolarizing factors that induce vascular relaxations by activation of smooth muscle apamin-sensitive, calcium-activated, small-conductance K+ channels causing hyperpolarization. In other arteries, the 12-LO metabolite 12-hydroxyeicosatetraenoic acid is synthesized by the vascular endothelium and relaxes smooth muscle by large-conductance, calcium-activated K+ channel activation. Thus formation of vasodilator eicosanoids derived from LO pathways contributes to the regulation of vascular tone, local blood flow, and blood pressure.

Na—Ca exchange and tension development in arterial smooth muscle

1973 ◽  
Vol 265 (867) ◽  
pp. 87-94 ◽  
Keyword(s):  
Smooth Muscle ◽  
Membrane Potential ◽  
Cell Membrane ◽  
Transport Mechanism ◽  
Vascular Tone ◽  
Choline Chloride ◽  
Pulmonary Arteries ◽  
Tension Development ◽  
45Ca Efflux ◽  
Regulation Of Vascular Tone

Replacement of external NaCl by LiCl, choline chloride or sucrose increased tension of rabbit aortic strips and pulmonary arteries despite little change in membrane potential. The Ca content of the aortic strips increased concomitantly with the tension development. A two- to threefold increment in 45Ca influx could be measured when external Na was removed. 45Ca efflux decreased in Na-free, Ca-free solutions where little or no tension developed and increased in Na-free, Ca-containing solution concomitantly with the increase in tension. The possible significance of a Ca transport mechanism in the cell membrane which depends on Na and Ca (Na-Ca exchange) for the regulation of vascular tone is discussed.

scholarly journals Vascular control of the CO2/H+ dependent drive to breathe

2020 ◽  
Author(s):  
CM Cleary ◽  
TS Moreira ◽  
AC Takakura ◽  
MT Nelson ◽  
TA Longden ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Tone ◽  
Vascular Reactivity ◽  
Muscle Cells ◽  
Vascular Control ◽  
Respiratory Behavior ◽  
Vascular Element ◽  
Regulation Of Vascular Tone

AbstractRespiratory chemoreceptors regulate breathing in response to changes in tissue CO2/H+. Blood flow is a fundamental determinant of tissue CO2/H+, yet little is known regarding how regulation of vascular tone in chemoreceptor regions contributes to respiratory behavior. Previously, we showed in rat that CO2/H+-vasoconstriction in the retrotrapezoid nucleus (RTN) supports chemoreception by a purinergic-dependent mechanism (Hawkins et al. 2017). Here, we show in mice that CO2/H+ dilates arterioles in other chemoreceptor regions, thus demonstrating CO2/H+ vascular reactivity in the RTN is unique. We also identify P2Y2 receptors in RTN smooth muscle cells as the substrate responsible for this response. Specifically, pharmacological blockade or genetic deletion of P2Y2 from smooth muscle cells blunted the ventilatory response to CO2, and re-expression of P2Y2 receptors only in RTN smooth muscle cells fully rescued the CO2/H+ chemoreflex. These results identify P2Y2 receptors in RTN smooth muscle cells as requisite determinants of respiratory chemoreception.Significance StatementDisruption of vascular control as occurs in cardiovascular disease leads to compromised chemoreceptor function and unstable breathing. Despite this, virtually nothing is known regarding how regulation of vascular tone in chemoreceptor regions contributes to respiratory behavior. Here, we identify P2Y2 receptors in RTN vascular smooth muscle cells as a novel vascular element of respiratory chemoreception. Identification of this mechanism may facilitate development of treatments for breathing problems including those associated with cardiovascular disease.

Ouabain augments Ca2+ transients in arterial smooth muscle without raising cytosolic Na+

2000 ◽  
Vol 279 (2) ◽  
pp. H679-H691 ◽  
Author(s):  
Assaf Arnon ◽  
John M. Hamlyn ◽  
Mordecai P. Blaustein
Keyword(s):  
Blood Flow ◽  
Smooth Muscle ◽  
Vascular Tone ◽  
Low Dose ◽  
Cardiovascular Effects ◽  
Ion Transporters ◽  
Resistance Arteries ◽  
Store Depletion ◽  
Low Concentrations ◽  
Small Resistance

Ouabain and other cardiotonic steroids (CTS) inhibit Na+ pumps and are widely believed to exert their cardiovascular effects by raising the cytosolic Na+ concentration ([Na+]cyt) and Ca2+. This view has not been rigorously reexamined despite evidence that low-dose CTS may act without elevating [Na+]cyt; also, it does not explain the presence of multiple, functionally distinct isoforms of the Na+ pump in many cells. We investigated the effects of Na+ pump inhibition on [Na+]cyt(with Na+ binding benzofuran isophthalate) and Ca2+ transients (with fura 2) in primary cultured arterial myocytes. Low concentrations of ouabain (3–100 nM) or human ouabain-like compound or reduced extracellular K+ augmented hormone-evoked mobilization of stored Ca2+ but did not increase bulk [Na+]cyt. Augmentation depended directly on external Na+, but not external Ca2+, and was inhibited by 10 mM Mg2+ or 10 μM La3+. Evoked Ca2+ transients in pressurized small resistance arteries were also augmented by nanomolar ouabain and inhibited by Mg2+. These results suggest that Na+ enters a tiny cytosolic space between the plasmalemma (PL) and the adjacent sarcoplasmic reticulum (SR) via an Mg2+- and La3+-blockable mechanism that is activated by SR store depletion. The Na+ and Ca2+ concentrations within this space may be controlled by clusters of high ouabain affinity (α3) Na+ pumps and Na/Ca exchangers located in PL microdomains overlying the SR. Inhibition of the α3 pumps by low-dose ouabain should raise the local concentrations of Na+ and Ca2+ and augment hormone-evoked release of Ca2+ from SR stores. Thus the clustering of small numbers of specific PL ion transporters adjacent to the SR can regulate global Ca2+ signaling. This mechanism may affect vascular tone and blood flow and may also influence Ca2+ signaling in many other types of cells.

Stretch-dependent (myogenic) tone in rabbit ear resistance arteries

1986 ◽  
Vol 250 (1) ◽  
pp. H87-H95 ◽  
Author(s):  
J. J. Hwa ◽  
J. A. Bevan
Keyword(s):  
Smooth Muscle ◽  
Vascular Tone ◽  
Mechanical Stretch ◽  
Myogenic Tone ◽  
Resistance Arteries ◽  
Physiological Regulation ◽  
Rabbit Ear ◽  
Arterial Tone

Rabbit ear resistance arteries are vessels with three to six layers of smooth muscle cells and an unstretched lumen diameter of 75-150 micron. Ring segments of these arteries, in response to mechanical stretch in vitro, developed a maintained tonic contraction. The stretch-dependent contraction achieved a plateau within 10-30 min. Smooth muscle relaxants, such as NaNO2 and papaverine, substitution of extracellular Ca2+ by subthreshold Ca2+ (25 microM), or exposure to the Ca2+ influx antagonist Mn2+ abolished the stretch-dependent tone. The extent of the tone was dependent on the level of the applied stretch and the extracellular Ca2+ concentration ( [Ca2+]o). The maximal tone developed at optimal stretch, and [Ca2+]o in the bath solution was 18.1 +/- 4.6% of the maximal contraction of the vessel to histamine. This level of tone is comparable to neurogenic tone developed in response to nerve stimulation within the physiological frequency range. The stretch-dependent tone is considered probably myogenic in origin, since it was present in arterial segments that had been chronically denervated by surgical sympathectomy, mechanically deprived of the endothelium, and multireceptor blocked (phenoxybenzamine, 10(-6) M). Our findings suggest first that the stretch-dependent tone is myogenic and may be similar to basal vascular tone arising from the stretch of arterial pressure and its changes in vivo. Second, the magnitude of myogenic tone is a function of the applied stretch and the [Ca2+]o. Finally, myogenic tone is important in the physiological regulation of arterial tone in the rabbit ear resistance arteries.

Sign in / Sign up

Export Citation Format

Share Document