The effect of alkaline pH and transmural pressure on arterial constriction and membrane potential of hypertensive cerebral arteries

1987 ◽  
Vol 408 (3) ◽  
pp. 239-242 ◽  
Author(s):  
John S. Smeda ◽  
Julian H. Lombard ◽  
Jane A. Madden ◽  
David R. Harder
Keyword(s):  
Membrane Potential ◽  
Cerebral Arteries ◽  
Transmural Pressure ◽  
Alkaline Ph ◽  
Arterial Constriction

Regulation of membrane potential and diameter by voltage-dependent K+ channels in rabbit myogenic cerebral arteries

1995 ◽  
Vol 269 (1) ◽  
pp. H348-H355 ◽  
Author(s):  
H. J. Knot ◽  
M. T. Nelson
Keyword(s):  
Smooth Muscle ◽  
Membrane Potential ◽  
Smooth Muscle Cells ◽  
Cerebral Arteries ◽  
Muscle Cells ◽  
Transmural Pressure ◽  
Muscle Membrane ◽  
K Channels ◽  
Wide Range ◽  
Voltage Dependent

The hypothesis that voltage-dependent K+ channels are involved in the regulation of arterial smooth muscle membrane potential and blood vessel diameter was tested by examining the effects of inhibitors [4-aminopyridine (4-AP) and 3,4-diaminopyridine (3,4-DAP)] of voltage-dependent K+ channels on the membrane potential and diameter of pressurized small (100- to 300-microns diam) cerebral arteries from rabbit. In response to graded elevations in transmural pressure (20-100 mmHg), the membrane potential of smooth muscle cells in these arteries depolarized and the arteries constricted. 4-AP (1 mM) and 3,4-DAP (1 mM) depolarized cerebral arteries by 19 and 21 mV, respectively, when they were subjected to a transmural pressure of 80 mmHg. 3-Aminopyridine (3-AP, 1 mM), which is a relatively poor inhibitor of voltage-dependent K+ channels, depolarized smooth muscle cells in the arteries by 1 mV. 4-AP and 3,4-DAP constricted pressurized (to 80 mmHg) cerebral arteries. 3-AP had little effect on arterial diameter. 4-AP increased the arterial constriction to transmural pressure over a wide range of pressures (40-90 mmHg). The effects of 4-AP and 3,4-DAP on membrane potential and diameter were not prevented by inhibitors of calcium channels, calcium-activated K+ channels, ATP-sensitive K+ channels, inward rectifier K+ channels, blockers of adrenergic, serotonergic, muscarinic, and histaminergic receptors, or removal of the endothelium. These results suggest that voltage-dependent K+ channels are involved in the regulation of membrane potential and response of small cerebral arteries to changes in intravascular pressure.

Abstract 170: Arginase Contributes to Delayed Constriction of Large Cerebral Arteries in a Model of Subarachnoid Hemorrhage

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Weiyun Sun ◽  
Kathleen K Kibler ◽  
Herman Kwansa ◽  
Ewa Kulikowicz ◽  
Weizhu Tang ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Ex Vivo ◽  
Cerebral Arteries ◽  
Arginase Activity ◽  
Male Rats ◽  
Control Value ◽  
Age Related ◽  
Arterial Constriction ◽  
Oxide Synthase ◽  
Nitric Oxide Synthase Activity

Introduction: Increased arginase activity can limit nitric oxide synthase activity and contribute to age-related increase in aortic stiffness. Hypothesis: Subarachnoid hemorrhage (SAH) produces a delayed increase in arginase activity that contributes to delayed decreases in diameter of major cerebral arteries. Methods: Male rats underwent injection of blood into the cisterna magna on day 0 and again on day 2. Shams had double injection of artificial CSF. Measurements of arginase activity on vessels in the Circle of Willis and pia matter were made with an assay based on the conversion of radiolabeled arginine to urea. Measurements of diameter of basilar, posterior (PCA), middle (MCA), and anterior (ACA) cerebral arteries were made ex vivo after perfusion with paraformaldehyde and black latex casting. Results: Arginase activity (nmol of urea/min/mg of protein) increased from the control value of 13±3 (±SE; n=17) to 24±6 (n=6) at 3 days, 36±14 (n=4) at 5 days, and 48±16 (n=9) at 7 days after SAH and then recovered at 10 days (14±5; n=4) and 14 days (18±6; n=5) after SAH. Infusion of the arginase inhibitor 2(S)-amino-6-boronohexanoic acid (ABH) for 7 days after SAH with an ip osmotic pump blocked the increase in arginase activity (10±2; n=4). Assessment of arterial diameter at 3, 5, 7, 10, and 14 days after SAH revealed the smallest diameters occurring at 7 days (except for MCA which occurred at 5 days). Continuous ip infusion of 10 mg/kg/day ABH significantly attenuated the decrease in diameter (μm) 7 days after SAH in PCA (sham = 249±9, n=8; SAH = 209±12, n=10; SAH+ABH = 255±9, n=6) and ACA (sham = 178±11; SAH = 141±11; SAH+ABH = 198±10). Effects on basilar artery were of marginal significance (P=0.065). Conclusion: SAH produces an increase in vascular arginase activity that is temporally related to delayed decreases in diameter of cerebral arteries. Inhibition of arginase activity prevents the decrease in diameter at 7 days after SAH, thereby indicating a contribution of arginase to delayed arterial constriction/remodeling in post-fixed arteries.

Neural mechanism underlying basilar arterial constriction by intracisternal L-NNA in anesthetized dogs

1993 ◽  
Vol 265 (1) ◽  
pp. H103-H107 ◽  
Author(s):  
N. Toda ◽  
K. Ayajiki ◽  
T. Okamura
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Cerebral Arteries ◽  
Neural Mechanism ◽  
Systemic Blood Pressure ◽  
Systemic Blood ◽  
Anesthetized Dogs ◽  
Arterial Constriction ◽  
Synthase Inhibitor

Basilar arterial diameters were angiographically measured in anesthetized dogs in which systemic blood pressure and heart rate were also monitored. Injections of NG-nitro-L-arginine (L-NNA), a NO synthase inhibitor, into the cisterna magna produced a significant, persistent decrease in arterial diameter, the effect being reversed by intracisternal injections of L-arginine. The vasoconstrictor effect of L-NNA was diminished in dogs treated with hexamethonium. On the other hand, treatment with phentolamine in a dose sufficient to lower blood pressure to a level similar to that attained with hexamethonium did not inhibit, but rather potentiated, the effect of intracisternal L-NNA. Nicotine injected into the vertebral artery significantly dilated the basilar artery. The effect was abolished by treatment with L-NNA applied intracisternally, the inhibition being reversed by the addition of L-arginine. Systemic blood pressure and heart rate were not altered by intracisternally applied L-NNA and L-arginine. These findings support the hypothesis that basilar arterial constriction caused by intracisternal L-NNA is associated with a suppression of NO synthesis in nitroxidergic nerves innervating the cerebroarterial wall rather than an elimination of basal release of NO from the endothelium. Functional importance of nitroxidergic vasodilator innervation in cerebral arteries in vivo is thus clarified.

Activators of protein kinase C decrease Ca2+ spark frequency in smooth muscle cells from cerebral arteries

1997 ◽  
Vol 273 (6) ◽  
pp. C2090-C2095 ◽  
Author(s):  
Adrian D. Bonev ◽  
Jonathan H. Jaggar ◽  
Michael Rubart ◽  
Mark T. Nelson
Keyword(s):  
Protein Kinase C ◽  
Membrane Potential ◽  
Protein Kinase ◽  
Cerebral Arteries ◽  
Outward Current ◽  
Transient Outward Current ◽  
Open Probability ◽  
Kinase C ◽  
Voltage Dependent ◽  
Channel Currents

Local Ca2+ transients (“Ca2+ sparks”) caused by the opening of one or the coordinated opening of a number of tightly clustered ryanodine-sensitive Ca2+-release (RyR) channels in the sarcoplasmic reticulum (SR) activate nearby Ca2+-dependent K+(KCa) channels to cause an outward current [referred to as a “spontaneous transient outward current” (STOC)]. These KCa currents cause membrane potential hyperpolarization of arterial myocytes, which would lead to vasodilation through decreasing Ca2+ entry through voltage-dependent Ca2+ channels. Therefore, modulation of Ca2+spark frequency should be a means to regulation of KCa channel currents and hence membrane potential. We examined the frequency modulation of Ca2+ sparks and STOCs by activation of protein kinase C (PKC). The PKC activators, phorbol 12-myristate 13-acetate (PMA; 10 nM) and 1,2-dioctanoyl- sn-glycerol (1 μM), decreased Ca2+ spark frequency by 72% and 60%, respectively, and PMA reduced STOC frequency by 83%. PMA also decreased STOC amplitude by 22%, which could be explained by an observed reduction (29%) in KCa channel open probability in the absence of Ca2+ sparks. The reduction in STOC frequency occurred in the presence of an inorganic blocker (Cd2+) of voltage-dependent Ca2+ channels. The reduction in Ca2+ spark frequency did not result from SR Ca2+ depletion, since caffeine-induced Ca2+ transients did not decrease in the presence of PMA. These results suggest that activators of PKC can modulate the frequency of Ca2+ sparks, through an effect on the RyR channel, which would decrease STOC frequency (i.e., KCa channel activity).

L-Malate transport and proton symport in vesicles prepared from Pseudomonas putida

1986 ◽  
Vol 64 (11) ◽  
pp. 1190-1194 ◽  
Author(s):  
F. R. Agbanyo ◽  
G. Moses ◽  
N. F. Taylor
Keyword(s):  
Membrane Potential ◽  
Pseudomonas Putida ◽  
Kinetic Analysis ◽  
Transport System ◽  
Electron Donor ◽  
Proton Transport ◽  
Proton Motive Force ◽  
Alkaline Ph ◽  
Proton Symport ◽  
Malate Transport

In vesicles from glucose-grown Pseudomonas putida, L-malate is transported by nonspecific physical diffusion. L-Malate also acts as an electron donor and generates a proton motive force (Δp) of 129 mV which is composed of a membrane potential (Δψ) of 60 mV and a ΔpH of 69 mV. In contrast, vesicles from succinate-grown cells (a) transport L-malate by a carrier-mediated system with a Km value of 14.3 mM and a Vmax of 313 nmol∙mg protein−1∙min−1, (b) generate no Δψ, ΔpH, or Δp when L-malate is the electron donor, and (c) produce an extravesicular alkaline pH during the transport of L-malate. A kinetic analysis of this L-malate-induced proton transport gives a Km value of 16 mM and a Vmax of 667 nmol H+∙mg protein−1∙min−1. This corresponds to a H+/L-malate ratio of 2.1. The failure to generate a Δp in these vesicles is considered, therefore, to be consistent with the induction in succinate-grown cells of an electrogenic proton symport L-malate transport system.

scholarly journals Membrane potential and Ca2+ concentration dependence on pressure and vasoactive agents in arterial smooth muscle: A model

2015 ◽  
Vol 146 (1) ◽  
pp. 79-96 ◽  
Author(s):  
Arthur Karlin
Keyword(s):  
Smooth Muscle ◽  
Membrane Potential ◽  
Cerebral Arteries ◽  
Ryanodine Receptors ◽  
Vessel Diameter ◽  
Bk Channels ◽  
Epoxyeicosatrienoic Acid ◽  
Arterial Smooth Muscle ◽  
Cl Channels ◽  
Protein Components

Arterial smooth muscle (SM) cells respond autonomously to changes in intravascular pressure, adjusting tension to maintain vessel diameter. The values of membrane potential (Vm) and sarcoplasmic Ca2+ concentration (Cain) within minutes of a change in pressure are the results of two opposing pathways, both of which use Ca2+ as a signal. This works because the two Ca2+-signaling pathways are confined to distinct microdomains in which the Ca2+ concentrations needed to activate key channels are transiently higher than Cain. A mathematical model of an isolated arterial SM cell is presented that incorporates the two types of microdomains. The first type consists of junctions between cisternae of the peripheral sarcoplasmic reticulum (SR), containing ryanodine receptors (RyRs), and the sarcolemma, containing voltage- and Ca2+-activated K+ (BK) channels. These junctional microdomains promote hyperpolarization, reduced Cain, and relaxation. The second type is postulated to form around stretch-activated nonspecific cation channels and neighboring Ca2+-activated Cl− channels, and promotes the opposite (depolarization, increased Cain, and contraction). The model includes three additional compartments: the sarcoplasm, the central SR lumen, and the peripheral SR lumen. It incorporates 37 protein components. In addition to pressure, the model accommodates inputs of α- and β-adrenergic agonists, ATP, 11,12-epoxyeicosatrienoic acid, and nitric oxide (NO). The parameters of the equations were adjusted to obtain a close fit to reported Vm and Cain as functions of pressure, which have been determined in cerebral arteries. The simulations were insensitive to ±10% changes in most of the parameters. The model also simulated the effects of inhibiting RyR, BK, or voltage-activated Ca2+ channels on Vm and Cain. Deletion of BK β1 subunits is known to increase arterial–SM tension. In the model, deletion of β1 raised Cain at all pressures, and these increases were reversed by NO.

KCa-channel blockade prevents sustained pressure-induced depolarization in rat mesenteric small arteries

1997 ◽  
Vol 272 (5) ◽  
pp. H2241-H2249 ◽  
Author(s):  
J. P. Wesselman ◽  
R. Schubert ◽  
E. D. VanBavel ◽  
H. Nilsson ◽  
M. J. Mulvany
Keyword(s):  
Smooth Muscle ◽  
Membrane Potential ◽  
Transmural Pressure ◽  
Muscle Membrane ◽  
Outer Diameter ◽  
Small Arteries ◽  
Pressure Elevation ◽  
Kca Channels ◽  
Smooth Muscle Membrane

In small blood vessels, elevation of transmural pressure induces myogenic constrictions and smooth muscle depolarization. The role of calcium-activated K+ channels (KCa channels) in these responses was examined in cannulated rat mesenteric small arteries. Inner and outer diameter were continuously monitored with a video technique. Smooth muscle membrane potential was recorded simultaneously using microelectrodes. To test for myogenic responsiveness, the transmural pressure was changed stepwise in the range between 10 and 120 mmHg. Pressure elevation induced moderate myogenic responses and significant depolarization, from -54.5 +/- 0.4 (SE) mV (n = 56) at 10 mmHg to -47.3 +/- 1.8 mV (n = 12) at 120 mmHg. Norepinephrine (NE, 0.67 and 10 microM) induced constriction and vasomotion, augmented myogenic responsiveness, and shifted the pressure-membrane potential relation to more depolarized values. Blockade of the Kca channels with charybdotoxin (ChTX) suppressed the responsiveness to pressure. In the absence of ChTX, with 0.67 microM NE, pressure elevation from 10 to 120 mmHg induced depolarization from -46.9 +/- 1.0 (n = 16) to -35.8 +/- 0.7 (n = 12) mV, whereas because of the myogenic response, the diameter increased only by 7%. In the presence of ChTX, with 0.3 microM NE, pressure changed the membrane potential from -41.0 +/- 1.1 (n = 12) to -37.8 +/- 0.7 mV (n = 4), which was not significant, and the diameter increased by 28%. These results demonstrate that blockade of KCa channels reduces responsiveness to pressure elevation. This suggests that pressure may induce depolarization and concomitant myogenic responsiveness by closure of KCa channels.

Alkaline pH shifts Ca2+ sparks to Ca2+waves in smooth muscle cells of pressurized cerebral arteries

2002 ◽  
Vol 283 (6) ◽  
pp. H2169-H2176 ◽  
Author(s):  
Thomas J. Heppner ◽  
Adrian D. Bonev ◽  
L. Fernando Santana ◽  
Mark T. Nelson
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Cerebral Arteries ◽  
Ryanodine Receptors ◽  
Muscle Cells ◽  
Alkaline Ph ◽  
Voltage Dependent ◽  
Intracellular Ca ◽  
A Minor ◽  
External Ph

The effects of external pH (7.0–8.0) on intracellular Ca2+ signals (Ca2+ sparks and Ca2+ waves) were examined in smooth muscle cells from intact pressurized arteries from rats. Elevating the external pH from 7.4 to 7.5 increased the frequency of local, Ca2+transients, or “Ca2+ sparks,” and, at pH 7.6, significantly increased the frequency of Ca2+ waves. Alkaline pH-induced Ca2+ waves were inhibited by blocking Ca2+ release from ryanodine receptors but were not prevented by inhibitors of voltage-dependent Ca2+ channels, phospholipase C, or inositol 1,4,5-trisphosphate receptors. Activating ryanodine receptors with caffeine (5 mM) at pH 7.4 also induced repetitive Ca2+ waves. Alkalization from pH 7.4 to pH 7.8–8.0 induced a rapid and large vasoconstriction. Approximately 82% of the alkaline pH-induced vasoconstriction was reversed by inhibitors of voltage-dependent Ca2+ channels. The remaining constriction was reversed by inhibition of ryanodine receptors. These findings indicate that alkaline pH-induced Ca2+ waves originate from ryanodine receptors and make a minor, direct contribution to alkaline pH-induced vasoconstriction.

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