Mechanism of impaired myogenic response in cerebral blood vessels during posthypoxic recovery

1987 ◽  
Vol 65 (2) ◽  
pp. 159-164 ◽  
Author(s):  
B. A. Mallick ◽  
D. Bose ◽  
T. Chau ◽  
B. Y. Ong
Keyword(s):  
Smooth Muscle ◽  
Basilar Artery ◽  
Sodium Pump ◽  
Rapid Reduction ◽  
Bathing Medium ◽  
Tension Level ◽  
Electrogenic Sodium Pump ◽  
Muscle Inhibition ◽  
Canine Basilar Artery ◽  
Series Of Experiments

Cerebral blood flow autoregulation is impaired in newborn animals when a brief period of hypoxia is followed by normoxia. Because myogenic mechanisms are widely thought to be responsible for autoregulation, this study examined the effect of hypoxia and reoxygenation on the isometric mechanical function of isolated cerebral (basilar) arterial smooth muscle made to contract rhythmically and thus simulate the behaviour of arterioles. Although at rest a small amount of active tension was present in these preparations, this tension was further increased and the muscle was rendered spontaneously rhythmic by treatment with 4-aminopyridine. Reduction of bath [Formula: see text] from 120 to 25 mmHg (1 mmHg = 133.32 Pa) caused an increase in tension followed by a return towards normal tension. At this time rhythmic oscillations gradually decreased in amplitude. Restoration of normal oxygen tension caused a rapid reduction and an undershoot in tension followed by recovery to normal level. Two possible mechanisms for this undershoot, which may be due to a decrease in myogenic responsiveness and therefore of autoregulatory function, were tested. 8-Phenyltheophylline, an antagonist of adenosine receptors, caused a decrease in the inhibitory mechanical effects of adenosine (10−6–10− M). However, in the presence of 8-phenyltheophylline, there was no change in the undershoot in tension caused by reoxygenation, thus ruling out involvement of adenosine released from the vessel in smooth muscle inhibition due to hypoxia. In a separate series of experiments, the role of an electrogenic sodium pump in causing the undershoot was tested. Treatment with 5-hydroxytryptamine in a K+ -free bathing medium caused an increase in basilar artery tension. When normal potassium concentration was restored the muscle relaxed with a transient undershoot below the basal tension level. In muscle preparations pretreated with ouabain (3 × 10−6 M), the K+-induced undershoot was abolished and replaced by a transient contraction. The same concentration of ouabain decreased by 92% the tension undershoot caused by reoxygenation. These experiments rule out participation of adenosine released from the blood vessel in the loss of myogenic tone during reoxygenation. The data also indicate that reactivation of the sodium pump may be responsible to some extent for the undershoot in tone during reoxygenation of isolated canine basilar artery.

Inhibition of the acetylcholine-induced relaxation of canine isolated basilar artery by potassium-conductance blockers

1991 ◽  
Vol 69 (6) ◽  
pp. 786-791 ◽  
Author(s):  
D. A. Elliott ◽  
M. Gu ◽  
B. Y. Ong ◽  
D. Bose
Keyword(s):  
Smooth Muscle ◽  
Sodium Nitroprusside ◽  
Basilar Artery ◽  
Sodium Pump ◽  
Potassium Conductance ◽  
K Channel ◽  
Relaxing Factor ◽  
Mechanical Removal ◽  
Canine Basilar Artery ◽  
Endothelium Derived Relaxing Factor

Canine basilar artery rings precontracted with 5-hydroxytryptamine (0.1–0.5 μM) relaxed in the presence of acetylcholine (25–100 μM), sodium nitroprusside (0.1 μM), or stimulation of the electrogenic sodium pump by restoration of extracellular K+ (4.5 mM) after K+- deprivation. Acetylcholine-induced relaxation is believed to be caused by the release of endothelium-derived relaxing factor (EDRF) and is prevented by mechanical removal of the endothelium, while relaxations induced by sodium nitroprusside or restarting of the sodium pump are endothelium-independent. Acetylcholine-induced relaxation was selectively blocked by pretreatment of the tissue with the nonselective K+ conductance inhibitors, 4-aminopyridine (4-AP, 3 mM), Ba2+ (1 mM), and tetraethylammonium (20 mM). 4-AP also blocked ACh-mediated relaxation in muscles contracted with elevated external K+. Relaxation of 5-hydroxytryptamine-induced contraction by sodium nitroprusside, or by addition of K+ to K+-deprived muscle, was not affected by 4-AP. Relaxation of basilar artery with acidified sodium nitrite solution (containing nitric oxide) was reduced by 4-AP. These results suggest that 4-AP and possibly Ba2+ inhibit acetylcholine-induced endothelium-dependent relaxation by inhibition of the action of EDRF on the smooth muscle rather than through inhibition of release of EDRF. The increase in K+ conductance involved in acetylcholine-induced relaxation is not due to ATP-inhibited K+ channels, as it is not blocked by glyburide (10−6 M). Endothelium-derived relaxant factor(s) may relax smooth muscle by mode(s) of action different from that of sodium nitroprusside or by hyperpolarization due to the electrogenic sodium pumping. Since 4-AP and similar agents are used to increase myogenic tone, the absence of the endothelium may be mistakenly assumed in the presence of these agents.Key words: Ba2+, blood vessels, endothelium-derived hyperpolarizing factor, endothelium-derived relaxing factor, glyburide, K channel, pinacidil, relaxation.

scholarly journals Activation of Protein Kinases in Canine Basilar Artery in Vasospasm

1999 ◽  
Vol 19 (1) ◽  
pp. 44-52 ◽  
Author(s):  
Hirokazu Fujikawa ◽  
Eiichi Tani ◽  
Ikuya Yamaura ◽  
Isao Ozaki ◽  
Katsuya Miyaji ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase ◽  
Tyrosine Kinase ◽  
Basilar Artery ◽  
Molecular Mechanisms ◽  
Kinase Inhibitor ◽  
Polyacrylamide Gel Electrophoresis ◽  
Intracellular Ca ◽  
Canine Basilar Artery ◽  
Kinase Pathway

Subarachnoid hemorrhage (SAH) often leads to a long-term narrowing of cerebral artery called vasospasm. To understand the molecular mechanisms in vasospasm, signal transduction of tyrosine kinase pathway and phosphorylation of myosin light chain (MLC) and calponin (CaP) in the basilar artery were studied. Vasospasm was produced in the canine basilar artery by a two-hemorrhage method, and vasocontraction was induced by a local application of KCl or serotonin to the basilar artery after a transclival exposure. Intracellular substrates of tyrosine kinase pathway, including Shc, Raf1, and extracellular-regulated kinases in the basilar artery, were activated after SAH, and the activation of Shc suggests stimulation of signal transductions from tyrosine kinase receptors, G-coupled receptors, or both. The activation of tyrosine kinase pathway in vasospasm also was supported by dose-dependent dilation of the spastic basilar artery on days 0 and 7 by topical application of genistein, a tyrosine kinase inhibitor, and associated marked inhibition of tyrosine phosphorylation of intracellular substrates, including Shc. In addition, the generation of protein kinase M, catalytic fragment of protein kinase Cα (PKCα), in vasospasm on days 0 and 7 was inhibited in response to genistein, indicating an inactivation of μ-calpain. It is suggested, therefore, that the reversal of vasospasm by genistein is closely associated with the restoration of intracellular Ca2+ levels. However, the increased activities of Raf1 and extracellular-regulated kinases in vasospasm were declined on day 7 compared with those on day 0 or 2, suggesting that the activation of tyrosine kinase pathway is more closely associated with the early stage of vasospasm than with the late stage of vasospasm. The analysis by pyrophosphate polyacrylamide gel electrophoresis (PPi-PAGE) demonstrated three MLC bands in vasospasm on days 2 and 7, as well as in KCl- and serotonin-induced vasocontraction. Since PPi-PAGE resolves smooth muscle MLC into three bands in the MLC kinase (MLCK)-mediated phosphorylation and into a single band in the PKC-mediated phosphorylation based on the phosphorylation state, the current results suggest that MLC in vasospasm is phosphorylated by MLCK but not by PKC. In basilar artery, CaP was significantly down-regulated, and in addition, significantly phosphorylated on serine and threonine residues only in vasospasm on days 2 and 7. Although the significance of CaP phosphorylations in vivo still is controversial, CaP down-regulation and phosphorylation may attenuate the inhibition of Mg2+-ATPase activity by CaP and induce a potential enhancement of smooth muscle contractility in delayed vasospasm. Since CaP is phosphorylated vivo by PKC, activated PKC in vasospasm may phosphorylate CaP. Thus, SAH stimulates tyrosine kinase pathway to increase intracellular Ca2+ and activate PKC, and the former activates MLCK to phosphorylate MLC, whereas the latter phosphorylates CaP but not MLC.

Monovalent Ion Specificity of the Electrogenic Sodium Pump in Vascular Smooth Muscle

1981 ◽  
Vol 166 (3) ◽  
pp. 457-461 ◽  
Author(s):  
R. C. Webb ◽  
W. E. Lockette ◽  
P. M. Vanhoutte ◽  
D. F. Bohr
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Sodium Pump ◽  
Ion Specificity ◽  
Electrogenic Sodium Pump ◽  
Monovalent Ion

Potassium and the recovery of splenic capsular smooth muscle after cold storage

1976 ◽  
Vol 54 (3) ◽  
pp. 322-326
Author(s):  
D. Bose ◽  
I. R. Innes
Keyword(s):  
Smooth Muscle ◽  
Ambient Temperature ◽  
Cold Storage ◽  
Sodium Pump ◽  
Intracellular Sodium ◽  
Free Medium ◽  
Bathing Medium ◽  
Cat Spleen ◽  
Sodium And Potassium ◽  
Low Ambient Temperature

Cat spleen capsular smooth muscle, depleted of potassium and enriched with sodium by cold storage in a potassium free medium, relaxed and underwent transient reduction in responsiveness to noradrenaline when potassium was introduced into the bathing medium. Both these effects could be blocked by ouabain, lithium substitution for sodium or low ambient temperature, suggesting possible involvement of the sodium pump. In the continued presence of potassium, relaxation was maintained but sensitivity to noradrenaline increased, possibly due to restoration of normal intracellular sodium and potassium concentrations.

scholarly journals Diltiazem-induced vasodilation of smooth muscle cells of the canine basilar artery

1982 ◽  
Vol 32 ◽  
pp. 184
Author(s):  
Shigeru Fujiwara ◽  
Yushi Ito ◽  
Takeo Itoh ◽  
Hikaru Suzuki ◽  
Hirosi Kuriyama
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Basilar Artery ◽  
Muscle Cells ◽  
Canine Basilar Artery

Isoprenaline-induced Relaxation of Smooth Muscle not due to Electrogenic Sodium Pumping

1972 ◽  
Vol 50 (4) ◽  
pp. 378-380 ◽  
Author(s):  
Deepak Bose ◽  
Ian R. Innes
Keyword(s):  
Smooth Muscle ◽  
Carotid Artery ◽  
Sodium Pump ◽  
Free Medium ◽  
Electrogenic Sodium Pump ◽  
Sodium Pumping ◽  
Stimulation Of

Ouabain or replacement of NaCl by LiCl abolishes the relaxation due to addition of KCl to sodium-rich cat carotid artery strips kept in a K+-free medium. Neither treatment antagonizes the relaxation due to β-adrenoceptor stimulation by l-isoprenaline. Unlike KCl-induced relaxation, the relaxation induced by l-isoprenaline is not due to stimulation of an electrogenic sodium pump.

scholarly journals DILTIAZEM-INDUCED VASODILATATION OF SMOOTH MUSCLE CELLS OF THE CANINE BASILAR ARTERY

1982 ◽  
Vol 75 (3) ◽  
pp. 455-467 ◽  
Author(s):  
SHIGERU FUJIWARA ◽  
YUSHI ITO ◽  
TAKEO ITOH ◽  
HIROSI KURIYAMA ◽  
HIKARU SUZUKI
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Basilar Artery ◽  
Muscle Cells ◽  
Canine Basilar Artery

scholarly journals Impaired Calcium Regulation of Smooth Muscle during Chronic Vasospasm following Subarachnoid Hemorrhage

1996 ◽  
Vol 16 (2) ◽  
pp. 334-341 ◽  
Author(s):  
Phyo Kim ◽  
Yuhei Yoshimoto ◽  
Masamitsu Iino ◽  
Sasaki Tomio ◽  
Takaaki Kirino ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Subarachnoid Hemorrhage ◽  
Intracellular Calcium ◽  
Basilar Artery ◽  
Calcium Concentration ◽  
Calcium Regulation ◽  
Control Group ◽  
Intracellular Calcium Level ◽  
Canine Basilar Artery ◽  
Chronic Vasospasm

The intracellular calcium level was determined in the canine basilar artery to investigate whether Ca2+regulation of its smooth muscle is altered during chronic vasospasm following subarachnoid hemorrhage. A double-hemorrhage model was used. The occurrence of vasospasm was confirmed angiographically 7 days after initial hemorrhage. The intracellular calcium concentration ([Ca2+]i) of smooth muscle was measured using Fura-2. Fluorescence to excitation at 340 and 356 nm was monitored and the ratio R340/356 was used as the indicator of [Ca2+]i. When the extracellular calcium concentration ([Ca2+]e) was increased from pCa 8 to 2, [Ca2+]i also increased. In the spastic arteries, the [Ca2+]e − [Ca2+]i curve was elevated as compared with the normal arteries. Treatment with ionomycin elevated the curve in the normal group, but it had little effect in the spastic arteries. Values of [Ca2+]i, calculated in multiples of Kd, were greater in the spastic arteries. Diltiazem (10;−5 mol/L) partially suppressed the augmented [Ca2+]i signal in the spastic arteries, whereas it did not affect the curve in the control group. These results indicate that calcium regulation of smooth muscle is impaired after subarachnoid hemorrhage, which may contribute to the pathogenesis of chronic vasospasm.

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