scholarly journals Mechanism of the Enhanced Vasoconstrictor Responses to Endothelin-1 in Canine Cerebral Arteries

1991 ◽  
Vol 11 (3) ◽  
pp. 371-379 ◽  
Author(s):  
Chiharu Tanoi ◽  
Yoshio Suzuki ◽  
Masato Shibuya ◽  
Kenichiro Sugita ◽  
Kaoru Masuzawa ◽  
...  
Keyword(s):  
Basilar Artery ◽  
Resting State ◽  
Mesenteric Artery ◽  
Cerebral Arteries ◽  
Mesenteric Arteries ◽  
Free Solution ◽  
Contractile Responses ◽  
Endothelin 1 ◽  
Voltage Dependent ◽  
Small Contraction

Vasoconstrictor effects of endothelin-1 (ET) were investigated in endothelium-denuded strips of cerebral (basilar and posterior cerebral) and mesenteric arteries of the dog. ET produced a concentration-dependent contraction in these arteries. Contractile responses to lower concentrations (below 3 × 10−10 M) of ET were significantly greater in the cerebral arteries than in the mesenteric artery. Inhibition by nifedipine of the contractile responses to ET was greater in the basilar artery than in the mesenteric artery. After the inhibition by 10−7 M nifedipine, the remaining responses to ET were similar in the two arteries. Cerebral arteries, but not the mesenteric artery, relaxed significantly from the resting level when placed in a Ca2+ -free solution containing 0.1 m M EGTA (0-Ca solution). Readdition of Ca2+ to the cerebral arteries placed in the 0-Ca solution caused a biphasic contraction that was sensitive to nifedipine. When 10−9 M ET was introduced before the Ca2+-induced contraction, this peptide produced only a very small contraction, but enhanced the Ca2+-induced contraction. The extent of the enhancement induced by ET was much greater in the cerebral arteries than in the mesenteric artery. These results indicate that the enhanced responses to ET in the cerebral arteries were dependent to a large extent on Ca2+ influx through voltage-dependent Ca2+ channels (VDCs). It is likely that the VDCs in these arteries are more activated in the resting state than those in the mesenteric artery.

scholarly journals Increased Ca2+ Influx in the Resting State Maintains the Myogenic Tone and Activates Charybdotoxin-Sensitive K+ Channels in Dog Basilar Artery

1993 ◽  
Vol 13 (6) ◽  
pp. 969-977 ◽  
Author(s):  
Masahisa Asano ◽  
Kaoru Masuzawa-Ito ◽  
Tomohiro Matsuda ◽  
Yoshio Suzuki ◽  
Hirofumi Oyama ◽  
...  
Keyword(s):  
Rate Constant ◽  
Basilar Artery ◽  
Resting State ◽  
Mesenteric Artery ◽  
Myogenic Tone ◽  
Efflux Rate ◽  
Channel Function ◽  
Voltage Dependent ◽  
Efflux Rate Constant ◽  
Resting Tone

We examined whether Ca2+ channel function in the resting state alters the resting tone and Ca2+ -activated K+ (KCa) channel function in dog basilar artery: data were compared with findings in the mesenteric artery. Isolated dog basilar artery maintained a myogenic tone; that is, the resting tone decreased when either the Krebs solution was replaced with a Ca2+ -free solution or nifedipine was added. The basal 45Ca influx in the resting state of the basilar artery was significantly increased compared with that in the mesenteric artery, and this increase in the basilar artery was reduced by nifedipine. The addition of charybdotoxin (ChTX), a blocker of large-conductance KCa channels, to the resting strips caused a concentration-dependent contraction in the basilar artery but not in the mesenteric artery. The ChTX-induced contraction in the basilar artery was abolished by nifedipine. In resting strips preloaded with 86Rb, the basal 86Rb efflux rate constant was significantly greater in the basilar artery than in the mesenteric artery. The addition of nifedipine to the resting strips decreased the basal 86Rb efflux rate constant only in the basilar artery. These results suggest that the transmembrane Ca2+ influx via L-type voltage-dependent Ca2+ channels was significantly increased in the resting state of the basilar artery and that the myogenic tone was therefore maintained and the ChTX-sensitive KCa channels were highly activated.

Expression of voltage-dependent K+ channel genes in mesenteric artery smooth muscle cells

1999 ◽  
Vol 277 (5) ◽  
pp. G1055-G1063 ◽  
Author(s):  
Chuanli Xu ◽  
Yanjie Lu ◽  
Guanghua Tang ◽  
Rui Wang
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Mesenteric Artery ◽  
Muscle Cells ◽  
Mesenteric Arteries ◽  
Delayed Rectifier ◽  
Kv Channel ◽  
Channel Proteins ◽  
Voltage Dependent ◽  
Encoding Genes

Molecular basis of native voltage-dependent K+(Kv) channels in smooth muscle cells (SMCs) from rat mesenteric arteries was investigated. The whole cell patch-clamp study revealed that a 4-aminopyridine-sensitive delayed rectifier K+ current ( I K) was the predominant K+ conductance in these cells. A systematic screening of the expression of 18 Kv channel genes using RT-PCR technique showed that six I K-encoding genes (Kv1.2, Kv1.3, Kv1.5, Kv2.1, Kv2.2, and Kv3.2) were expressed in mesenteric artery. Although no transient outward Kv currents ( I A) were recorded in the studied SMCs, transcripts of multiple I A-encoding genes, including Kv1.4, Kv3.3, Kv3.4, Kv4.1, Kv4.2, and Kv4.3 as well as I A-facilitating Kv β-subunits (Kvβ1, Kvβ2, and Kvβ3), were detected in mesenteric arteries. Western blot analysis demonstrated that four I K-related Kv channel proteins (Kv1.2, Kv1.3, Kv1.5, and Kv2.1) were detected in mesenteric artery tissues. The presence of Kv1.2, Kv1.3, Kv1.5, and Kv2.1 channel proteins in isolated SMCs was further confirmed by immunocytochemistry study. Our results suggest that the native I K in rat mesenteric artery SMCs might be generated by heteromultimerization of Kv genes.

scholarly journals Endotoxin Decreases the Contractile Responses of the Porcine Basilar Artery to Vasoactive Substances

1993 ◽  
Vol 13 (4) ◽  
pp. 712-719 ◽  
Author(s):  
Masami Ueno ◽  
Tony J.-F. Lee
Keyword(s):  
Endothelial Cells ◽  
Basilar Artery ◽  
Muscle Tone ◽  
Cerebral Arteries ◽  
Contractile Responses ◽  
Vasoactive Substances ◽  
Basilar Arteries ◽  
Arterial Reactivity ◽  
Lps Treatment

The effects of endotoxin (lipopolysaccharide; LPS) on the reactivity of isolated porcine basilar artery were examined using in vitro tissue bath techniques. The active muscle tone of the basilar arterial rings with or without endothelial cells induced by U46619 (1 μ M) reached a plateau in 15 min, which was stable for the first hour and gradually decreased during the next 5 h. This time-dependent decrease in tone was significantly potentiated in the presence of LPS (20 μg/ml). The potentiation by LPS was blocked by Nw-nitro-l-arginine (l-NNA; 60 μ M), methylene blue (10 μ M), and dexamethasone (1 μ M) but not by hemoglobin (1 μ M). The effect of l-NNA was readily reversed by l-arginine but not by d-arginine. Furthermore, the contractile responses of porcine basilar arterial rings with or without intact endothelium to U46619 and KCl were decreased following incubation with LPS (20 μg/ml) for 4 h. Similar hyporeactivity was observed in cold storage–denervated cerebral arteries incubated with LPS for 4 h. This decrease in contractile responses in LPS-treated rings was reversed by 60 μ M l-NNA and 1 μ M dexamethasone. These results indicate that LPS treatment renders the porcine basilar arteries hyporesponsive to vasoconstrictors. Since effects of LPS were not modified by the presence of endothelial cells and perivascular neurons, the alteration in cerebral arterial reactivity may be due in part to an enhanced formation of nitric oxide from l-arginine in the vascular smooth muscle cells.

Cromakalim and pinacidil dilate small mesenteric arteries but not small cerebral arteries

1991 ◽  
Vol 261 (2) ◽  
pp. H287-H291 ◽  
Author(s):  
J. G. McCarron ◽  
J. M. Quayle ◽  
W. Halpern ◽  
M. T. Nelson
Keyword(s):  
Blood Pressure ◽  
Systolic Blood Pressure ◽  
Mesenteric Artery ◽  
Cerebral Arteries ◽  
Mesenteric Arteries ◽  
Membrane Hyperpolarization ◽  
K Channels ◽  
Muscle Types ◽  
External K

Small elevations in external K+ hyperpolarize and dilate small cerebral arteries. The hyperpolarization and dilation to K+ are blocked by barium (less than 0.1 mM). Since membrane hyperpolarization appears to be an important mechanism for dilation of these small cerebral arteries, we investigated the effects of the hyperpolarizing vasodilators, cromakalim and pinacidil, on isolated pressurized rat cerebral arteries (diameter of 158 +/- 5 microns at 50% of the systolic blood pressure). Cromakalim and pinacidil, which are potent relaxants of a variety of muscle types, were without effect on posterior cerebral arteries at concentrations that completely dilate similarly sized rat mesenteric arteries (diameter 134 +/- 6 microns at 50% of the systolic blood pressure). The mesenteric artery dilation to cromakalim and pinacidil was reversed by glibenclamide. However, unlike the cerebral arteries, mesenteric arteries did not exhibit a barium-sensitive dilation to external K+. Thus it appears that there may be differences in the types of K+ channels that are activated by dilating mechanisms in small cerebral and mesenteric arteries.

Role of Cl− current in endothelin-1-induced contraction in rabbit basilar artery

2001 ◽  
Vol 281 (5) ◽  
pp. H2159-H2167 ◽  
Author(s):  
Yun Dai ◽  
John H. Zhang
Keyword(s):  
Basilar Artery ◽  
Methanesulfonic Acid ◽  
Isometric Tension ◽  
Channel Blockers ◽  
Free Solution ◽  
Bicarbonate Buffer ◽  
Endothelin 1 ◽  
New Zealand White Rabbits ◽  
Basilar Arteries

Cl− efflux induces depolarization and contraction of smooth muscle cells. This study was undertaken to explore the role of Cl− channels in endothelin-1 (ET-1)-induced contraction in rabbit basilar artery. Male New Zealand White rabbits ( n = 26), weighing 1.8–2.5 kg, were euthanized by an overdose of pentobarbital. The basilar arteries were removed for isometric tension recording. ET-1 produced a concentration-dependent contraction of the rabbit basilar artery in the normal Cl− Krebs-Henseleit bicarbonate buffer (123 mM Cl−). The ET-1-induced contraction was reduced by the following manipulations: 1) inhibition of Na+-K+-2Cl− cotransporter with bumetanide (3 × 10−5 and 10−4 M), 2) bicarbonate-free solution to disable Cl−/HCO[Formula: see text] exchanger, and 3) preincubation of rings with the Cl− channel blockers niflumic acid, 5-nitro-2-(3-phenylpropylamino)benzoic acid, and indanyloxyacetic acid 94. The ET-1-induced contraction was enhanced by substitution of extracellular Cl− (10 mM) with methanesulfonic acid (113 mM). Cl− channels are involved in ET-1-induced contraction in the rabbit basilar artery.

Alteration in voltage-dependent calcium channels in dog basilar artery after subarachnoid hemorrhage

2010 ◽  
Vol 113 (4) ◽  
pp. 870-880 ◽  
Author(s):  
Elena Nikitina ◽  
Ayako Kawashima ◽  
Masataka Takahashi ◽  
Zhen-Du Zhang ◽  
Xueyuan Shang ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Subarachnoid Hemorrhage ◽  
Basilar Artery ◽  
Low Voltage ◽  
Cerebral Arteries ◽  
Isometric Tension ◽  
Dose Effect ◽  
Voltage Dependent ◽  
Channel Currents ◽  
Number Of Cells

Object The L-type Ca++ channel antagonists like nimodipine have limited efficacy against vasospasm after subarachnoid hemorrhage (SAH). The authors tested the hypothesis that this is because SAH alters these channels, rendering them less responsible for contraction. Methods Basilar artery smooth muscle cells were isolated 4, 7, and 21 days after SAH in dogs, and Ca++ channel currents were recorded in 10-mmol/L barium. Proteins for α1 subunits of L-type Ca++ channels were measured by immunoblotting and isometric tension recordings done on rings of the basilar artery. Results High voltage–activated (HVA) Ca++ channel currents were significantly decreased and low voltage–activated (LVA) currents increased during vasospasm 4, 7, and 21 days after SAH (p < 0.05). Vasospasm was associated with a significant decrease in the number of cells with negligible LVA current while the number of cells in which the LVA current formed greater than 50% of the maximal current increased (p < 0.01). Window currents through LVA and HVA channels were significantly reduced. All changes correlated with the severity of vasospasm. There was an increase in protein for Cav3.1 and Cav3.3 α1 subunits that comprise T-type Ca++ channels, a decrease in L-type (Cav1.2 and Cav1.3) and an increase in R-type (Cav2.3) Ca++ channel α1 subunits. Functionally, however, isometric tension studies showed vasospastic arteries still relaxed with nimodipine. Conclusions Voltage-dependent Ca++ channels are altered in cerebral arteries after SAH. While decreased L-type channels may account for the lack of efficacy of nimodipine clinically, there may be other reasons such as inadequate dose, effect of nimodipine on other cellular targets, and mechanisms of vasospasm other than smooth muscle contraction mediated by activation of L-type Ca++ channels.

Actions of bradykinin on isolated cerebral and peripheral arteries

1977 ◽  
Vol 232 (3) ◽  
pp. H267-H274
Author(s):  
N. Toda
Keyword(s):  
Smooth Muscle ◽  
Internal Carotid ◽  
Direct Action ◽  
Cerebral Arteries ◽  
Mesenteric Arteries ◽  
External Carotid ◽  
Peripheral Arteries ◽  
Prostaglandin F2alpha ◽  
Contractile Responses ◽  
Contraction And Relaxation

The addition of bradykinin (BK) caused a dose-related contraction in helical strips of canine cerebral, internal carotid, external carotid, and femoral arteries, while the peptide elicited a relaxation in canine coronary, renal, and mesenteric arteries contracted with 5+ or prostaglandin F2alpha. In contrast to canine cerebral arteries, human cerebral arteries contracted with K+ or prostaglandin relaxed with BK. Contractile responses of canine cerebral arteries to BK were not influenced by phentolamine, diphenhydramine, and methysergide, but were attenuated by aspirin and indomethacin. Contractions induced by K+ were not or only slightly inhibited by these anti-inflammatory agents. Polyphloretin phosphate failed to reduce BK-induced contractions. Relaxing effects of BK on canine coronary arterial strips were not altered by atropine, propranolol, metiamide, and aminophylline, but were inhibited by aspirin and indomethacin. Adenosine-induced relaxation was unaffected by the latter two agents. It may be concluded that adrenergic, cholinergic, histaminergic, and adenosine-related mechanisms are not involved in the genesis of BK-induced contraction and relaxation. Contractile responses of canine cerebral arteries to BK do not appear to derive from prostaglandins released, but rather from a direct action on vascular smooth muscle cells.

scholarly journals Upregulation of Relaxin after Experimental Subarachnoid Hemorrhage in Rabbits

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Yuichiro Kikkawa ◽  
Satoshi Matsuo ◽  
Ryota Kurogi ◽  
Akira Nakamizo ◽  
Masahiro Mizoguchi ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Vasospasm ◽  
Basilar Artery ◽  
Messenger Rna ◽  
Cerebral Arteries ◽  
Enzyme Linked Immunosorbent Assay ◽  
Endothelin 1 ◽  
Basilar Arteries ◽  
Experimental Subarachnoid Hemorrhage

Background. Although relaxin causes vasodilatation in systemic arteries, little is known about its role in cerebral arteries. We investigated the expression and role of relaxin in basilar arteries after subarachnoid hemorrhage (SAH) in rabbits.Methods. Microarray analysis with rabbit basilar artery RNA was performed. Messenger RNA expression of relaxin-1 and relaxin/insulin-like family peptide receptor 1 (RXFP1) was investigated with quantitative RT-PCR. RXFP1 expression in the basilar artery was investigated with immunohistochemistry. Relaxin concentrations in cerebrospinal fluid (CSF) and serum were investigated with an enzyme-linked immunosorbent assay. Using human brain vascular smooth muscle cells (HBVSMC) preincubated with relaxin, myosin light chain phosphorylation (MLC) was investigated with immunoblotting after endothelin-1 stimulation.Results. After SAH, RXFP1 mRNA and protein were significantly downregulated on day 3, whereas relaxin-1 mRNA was significantly upregulated on day 7. The relaxin concentration in CSF was significantly elevated on days 5 and 7. Pretreatment with relaxin reduced sustained MLC phosphorylation induced by endothelin-1 in HBVSMC.Conclusion. Upregulation of relaxin and downregulation of RXFP1 after SAH may participate in development of cerebral vasospasm. Downregulation of RXFP1 may induce a functional decrease in relaxin activity during vasospasm. Understanding the role of relaxin may provide further insight into the mechanisms of cerebral vasospasm.

scholarly journals Electrical and Mechanical Changes during Anoxic Contractions of the Isolated Canine Basilar Artery

1993 ◽  
Vol 13 (3) ◽  
pp. 498-502 ◽  
Author(s):  
Tetsuhiko Nagao ◽  
Paul M. Vanhoutte
Keyword(s):  
Membrane Potential ◽  
Basilar Artery ◽  
Membrane Depolarization ◽  
Isometric Tension ◽  
Free Solution ◽  
High K ◽  
Voltage Dependent ◽  
Canine Basilar Artery

Isometric tension and membrane potential were measured to determine the electrophysiological events occurring during anoxia in the isolated canine basilar artery. Anoxia induced transient contractions which were inhibited by the Ca2+-channel inhibitor, diltiazem, and were abolished in Ca2+-free solution. Anoxic contractions were accompanied by membrane depolarizations, which were resistant to diltiazem. When matched contractions were obtained with anoxia and high K+, the level of membrane depolarization was smaller during anoxic contractions. These results support the importance of voltage-dependent Ca2 + influx in the generation of anoxic contractions in the canine basilar artery. However, membrane depolarization does not fully account for these anoxic contractions.

Sign in / Sign up

Export Citation Format

Share Document