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.

Manipulation of chloride flux affects histamine-induced contraction in rabbit basilar artery

2002 ◽  
Vol 282 (4) ◽  
pp. H1427-H1436 ◽  
Author(s):  
Yun Dai ◽  
John H. Zhang
Keyword(s):  
Smooth Muscle ◽  
Receptor Antagonist ◽  
Basilar Artery ◽  
Indoleacetic Acid ◽  
Isometric Tension ◽  
Chloride Flux ◽  
Pentobarbital Sodium ◽  
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− flux in histamine-induced contraction in the rabbit basilar artery. Male New Zealand White rabbits ( n = 16) weighing 1.8–2.5 kg were euthanized by an overdose of pentobarbital sodium. The basilar arteries were removed for isometric tension recording. Histamine produced a concentration-dependent contraction that was attenuated by the H1 receptor antagonist chlorpheniramine (10−8 M) but not by the H2 receptor antagonist cimetidine (3 × 10−6 M) in normal Cl−Krebs-Henseleit bicarbonate solution (123 mM Cl−). The histamine-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 HEPES solution to disable Cl−/HCO[Formula: see text] exchanger, and 3) blockade of Cl− channels with the use of niflumic acid, 5-nitro-2-(3-phenylpropylamino) benzoic acid, and indoleacetic acid 94 R-(+)-methylindazone. In addition, substitution of extracellular Cl− (10 mM) with methanesulfonate acid (113 mM) transiently enhanced histamine-induced contraction. Manipulation of Cl− flux affects histamine-induced contraction in the rabbit basilar artery.

Endothelial L-arginine pathway and relaxations to vasopressin in canine basilar artery

1993 ◽  
Vol 264 (2) ◽  
pp. H413-H418 ◽  
Author(s):  
F. Cosentino ◽  
J. C. Sill ◽  
Z. S. Katusic
Keyword(s):  
Nitric Oxide ◽  
Basilar Artery ◽  
Isometric Tension ◽  
Nitric Oxide Donor ◽  
Basal Tone ◽  
Basilar Arteries ◽  
Canine Basilar Artery ◽  
Subsequent Activation ◽  
Oxide Synthase

Experiments were designed to determine the role of the L-arginine pathway in endothelium-dependent relaxations to vasopressin. The effects of L-arginine analogues NG-nitro-L-arginine (L-NNA), NG-nitro-L-arginine methyl ester (L-NAME), and NG-monomethyl-L-arginine (L-NMMA) on basal and vasopressin-induced activity of nitric oxide synthase were studied in isolated canine basilar arteries. Rings with and without endothelium were suspended for isometric tension recording in Krebs-Ringer bicarbonate solution bubbled with 94% O2-6% CO2 (37 degrees C, pH 7.4). Radioimmunoassay was used to determine the level of guanosine 3',5'-cyclic monophosphate (cGMP). All experiments were performed in the presence of indomethacin, a cyclooxygenase inhibitor. L-NAME and L-NMMA caused endothelium-dependent contractions and inhibited basal production of cGMP. In contrast, L-NNA did not affect basal tone or basal production of cGMP. L-Arginine analogues inhibited relaxations to vasopressin but did not affect relaxations to a nitric oxide donor, molsidomine (SIN-1). The effects of L-NNA, L-NAME, and L-NMMA were reversed in the presence of L-arginine. The relaxations to vasopressin were associated with an increase of cGMP levels in the arterial wall. This effect of vasopressin was inhibited in the presence of L-NNA. These studies suggest that the relaxations to vasopressin are mediated by activation of the endothelial L-arginine pathway, leading to increased production of nitric oxide, with subsequent activation of guanylate cyclase in smooth muscle cells. In canine basilar artery, L-NAME and L-NMMA are nonselective inhibitors of both basal and stimulated production of nitric oxide, whereas L-NNA selectively inhibits vasopressin-induced activation of the L-arginine pathway.

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 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 The Functional and Structural Changes in the Basilar Artery Due to Overpressure Blast Injury

2015 ◽  
Vol 35 (12) ◽  
pp. 1950-1956 ◽  
Author(s):  
Hale Z Toklu ◽  
Judy Muller-Delp ◽  
Zhihui Yang ◽  
Şehkar Oktay ◽  
Yasemin Sakarya ◽  
...  
Keyword(s):  
Basilar Artery ◽  
Vascular Function ◽  
Structural Changes ◽  
Sprague Dawley ◽  
Endothelin 1 ◽  
Msec Duration ◽  
Basilar Arteries ◽  
Wave Induced ◽  
Endothelial Nitric Oxide ◽  
Cerebral Vascular

Overpressure blast-wave induced brain injury (OBI) leads to progressive pathophysiologic changes resulting in a reduction in brain blood flow, blood brain barrier breakdown, edema, and cerebral ischemia. The aim of this study was to evaluate cerebral vascular function after single and repeated OBI. Male Sprague-Dawley rats were divided into three groups: Control (Naive), single OBI (30 psi peak pressure, 1 to 2 msec duration), and repeated (days 1, 4, and 7) OBI (r-OBI). Rats were killed 24 hours after injury and the basilar artery was isolated, cannulated, and pressurized (90 cm H2O). Vascular responses to potassium chloride (KCl) (30 to 100 mmol/L), endothelin-1 (10−12 to 10−7 mol/L), acetylcholine (ACh) (10−10 to 10−4 mol/L) and diethylamine-NONO-ate (DEA-NONO-ate) (10−10 to 10−4 mol/L) were evaluated. The OBI resulted in an increase in the contractile responses to endothelin and a decrease in the relaxant responses to ACh in both single and r-OBI groups. However, impaired DEA-NONO-ate-induced vasodilation and increased wall thickness to lumen ratio were observed only in the r-OBI group. The endothelin-1 type A (ETA) receptor and endothelial nitric oxide synthase (eNOS) immunoreactivity were significantly enhanced by OBI. These findings indicate that both single and r-OBI impairs cerebral vascular endothelium-dependent dilation, potentially a consequence of endothelial dysfunction and/or vascular remodelling in basilar arteries after OBI.

Involvement of phospholipase C in endothelin 1–induced stimulation of Ca++ channels and basilar artery contraction in rabbits

2006 ◽  
Vol 105 (2) ◽  
pp. 288-293 ◽  
Author(s):  
Yoshifumi Kawanabe ◽  
Tomoh Masaki ◽  
Nobuo Hashimoto
Keyword(s):  
Phospholipase C ◽  
Essential Role ◽  
Ca Channels ◽  
Endothelin 1 ◽  
Nonselective Cation Channels ◽  
Basilar Arteries ◽  
Independent Cascade ◽  
Dependent Pathway ◽  
Stimulation Of

Object Endothelin 1 (ET-1) is a major cause of cerebral vasospasm after subarachnoid hemorrhage (SAH), and extracellular Ca++ influx plays an essential role in ET-1–induced vasospasm. The authors recently demonstrated that ET-1 activates two types of Ca++-permeable nonselective cation channels (designated NSCC-1 and NSCC-2) and a store-operated Ca++ channel (SOCC) in vascular smooth-muscle cells located in the basilar arteries (BAs) of rabbits. In the present study, they investigate the effects of phospholipase C (PLC) on ET-1–induced activation of these Ca++ channels and BA contraction by using the PLC inhibitor U73122. Methods To determine which Ca++ channels are activated via a PLC-dependent pathway, these investigators monitored the intracellular free Ca++ concentration ([Ca++]i). The role of PLC in ET-1–induced vascular contraction was examined by performing a tension study of rabbit BA rings. The U73122 inhibited the ET-1–induced transient increase in [Ca++]i, which resulted from mobilization of Ca++; from the intracellular store. Phospholipase C also inhibited ET-1–induced extracellular Ca++ influx through the SOCC and NSCC-2, but not through the NSCC-1. The U73122 inhibited the ET-1–induced contraction of the rabbit BA rings, which depended on extracellular Ca++ influx through the SOCC and NSCC-2. Conclusions These results indicate the following. 1) The SOCC and NSCC-2 are stimulated by ET-1 via a PLC-dependent cascade whereas NSCC-1 is stimulated via a PLC-independent cascade. 2) The PLC is involved in the ET-1–induced contraction of rabbit BA rings, which depends on extracellular Ca++ influx through the SOCC and NSCC-2.

Endothelium-dependent relaxation and experimental atherosclerosis in the rabbit aorta

1986 ◽  
Vol 64 (11) ◽  
pp. 1451-1453 ◽  
Author(s):  
N. Sreeharan ◽  
R. L. Jayakody ◽  
M. P. J. Senaratne ◽  
A. B. R. Thomson ◽  
C. T. Kappagoda
Keyword(s):  
Rabbit Aorta ◽  
Experimental Atherosclerosis ◽  
Isometric Tension ◽  
Dependent Manner ◽  
Bicarbonate Buffer ◽  
New Zealand White Rabbits ◽  
Set Up ◽  
And Control ◽  
Dose Dependent ◽  
Endothelium Dependent Relaxation

This study was undertaken to determine whether the production or release of the endothelium-dependent relaxatory factor is impaired in atherosclerotic New Zealand White rabbits. Atherosclerosis was induced by feeding a diet containing 2% cholesterol for 6 weeks. The production or release of endothelium-dependent relaxatory factor was assayed as follows. A 5-cm length of aorta donor was perfused with Krebs–bicarbonate buffer and the perfusate drained over a deendothelialized ring of recipient aorta set up for recording isometric tension. The recipient was precontracted with norepinephrine (0.2 μmol/L) in the perfusate. When acetylcholine was added to the perfusate, the recipient relaxed in a dose-dependent manner. This assay was used to compare the relaxatory responses produced in recipient rings by adding acetylcholine to donors from atherosclerotic and control rabbits. The relaxation produced by atherosclerotic donors were smaller than those generated by control donors (16.5 ± 4.9 vs. 32.7 ± 5.3%; n = 10, p < 0.05). It is suggested that in atherosclerotic rabbits the ability of aortic endothelium to produce or release endothelium-dependent relaxatory factor is impaired.

Erg K+ channels modulate contractile activity in the bovine epididymal duct

2008 ◽  
Vol 294 (3) ◽  
pp. R895-R904 ◽  
Author(s):  
Marco Mewe ◽  
Iris Wulfsen ◽  
Anna M. E. Schuster ◽  
Ralf Middendorff ◽  
Günter Glassmeier ◽  
...  
Keyword(s):  
Calcium Release ◽  
Calcium Influx ◽  
Contractile Activity ◽  
Physiological Role ◽  
Inhibitory Effect ◽  
Isometric Tension ◽  
Channel Blockers ◽  
Current Increase ◽  
Epididymal Duct

The expression and functional role of ether-à-go-go-related gene (erg) K+ channels were examined in the bovine epididymal duct. Sperm transit through the epididymal duct relies on spontaneous phasic contractions (SC) of the peritubular smooth muscle wall. Isometric tension studies revealed SC-enhancing effects of the erg channel blockers E-4031, dofetilide, cisapride, and haloperidol and SC-suppressing effects of the activator NS-1643. In the corpus epididymidis, EC50 values of 32 nM and 8.3 μM were determined for E-4031 and NS-1643, respectively. E-4031 was also able to elicit contraction in epithelium-denuded corpus segments, which lacked SC. In the cauda region, E-4031 and NS-1643 exerted effects on agonist-induced contraction similar to those observed in the proximal duct. Experiments with nifedipine and thapsigargin suggested that the excitatory effects of E-4031 depended mainly on external calcium influx and not on intracellular calcium release. Western blot and RT-PCR assays revealed the expression of both, erg1a and erg1b, in all duct regions. Because erg1b appears to predominate in the epididymal duct, patch-clamp experiments were performed on heterologously expressed erg1b channels to investigate the sensitivity of this splice variant to NS-1643. In contrast to its effects on erg1a, NS-1643 induced a concentration-dependent current increase mainly due to a marked leftward shift in erg1b channel activation by ∼30 mV at 10 μM, explaining the inhibitory effect of the drug on epididymal SC. In summary, these data provide strong evidence for a physiological role of erg1 channels in regulating epididymal motility patterns.

An in vitro comparative study of conducting vessels and penetrating arterioles after experimental subarachnoid hemorrhage in the rabbit

1992 ◽  
Vol 77 (1) ◽  
pp. 113-119 ◽  
Author(s):  
Dennis G. Vollmer ◽  
Masakazu Takayasu ◽  
Ralph G. Dacey
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Basilar Artery ◽  
Isometric Tension ◽  
Channel Blockers ◽  
Cerebral Microvessels ◽  
Content Type ◽  
Large Arteries ◽  
Experimental Subarachnoid Hemorrhage ◽  
Fine Print

✓ The reactivity of rabbit basilar artery and penetrating arteriolar microvessels was studied in vitro using an isometric-tension measurement technique and an isolated perfused arteriole preparation, respectively. Comparisons were made between reactivities of normal vessels and those obtained from animals subjected to experimental subarachnoid hemorrhage (SAH) 3 days prior to examination. Subarachnoid hemorrhage produced significant increases in basilar artery contraction in response to increasing concentrations of serotonin (5-hydroxytryptamine) (10−9 to 10−5 M) and prostaglandin F2α (10−9 to 10−5 M) when compared to normal arteries. In addition, SAH attenuated the relaxing effect of acetylcholine following serotonin-induced contraction and of adenosine triphosphate after KCl-induced basilar artery contractions. In contrast to the changes observed in large arteries, cerebral microvessels did not demonstrate significant differences in spontaneous tone or in reactivity to a number of vasoactive stimuli including application of calcium, serotonin, and acetylcholine. On the other hand, small but significant changes in arteriolar responsiveness to changes in extraluminal pH and to application of KCl were noted. Findings from this study suggest that intracerebral resistance vessels of the cerebral microcirculation are not greatly affected by the presence of subarachnoid clot, in contrast to the large arteries in the basal subarachnoid space. The small changes that do occur are qualitatively different from those observed for large arteries. These findings are consistent with the observation of significant therapeutic benefit with the use of calcium channel blockers without changes in angiographically visible vasospasm in large vessels. It is likely, therefore, that calcium antagonists may act to decrease total cerebrovascular resistance at the level of the relatively unaffected microcirculation after SAH without changing large vessel diameter.

Abstract 643: Heterozygous Endothelial Endothelin-1 Overexpression Potentiates Endothelium-Dependent Contractions in the Carotid Arteries of Obese Mice

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Oliver Baretella ◽  
Sookja K Chung ◽  
Aimin Xu ◽  
Paul M Vanhoutte
Keyword(s):  
Carotid Arteries ◽  
Receptor Activation ◽  
Isometric Tension ◽  
Endothelin 1 ◽  
Glucose Levels ◽  
Diet Induced Obesity ◽  
Tp Receptor ◽  
Carotid Arterial ◽  
Vasoconstrictor Peptide

Elevated plasma levels of the vasoconstrictor peptide endothelin-1 (ET-1) are associated with cardiovascular risk factors such as obesity, diabetes and hypertension, in which endothelium-dependent contractions are prominent. Exogenous ET-1 promotes the release of endothelium-derived contracting factors (EDCF), but the role of endogenously produced ET-1 in these processes is unknown. Therefore, mice with tie-1 promoter driven endothelium-restricted heterozygous overexpression of ppET-1 (TET+/-) and WT littermates were kept on standard chow as lean controls or administered a high fat diet for 30 weeks to induce obesity. At sacrifice, fasting glucose levels were significantly elevated in obese animals (8.3±0.3 vs. 5.3±0.2 mmol/l in lean controls, n =6, P <0.001). Isometric tension was measured in aortic and carotid arterial rings in wire myographs. In phenylephrine-contracted aortic rings, endothelium-dependent and −independent relaxations to acetylcholine and sodium nitroprusside, respectively, were unaltered between groups. In carotid arteries, the potency of phenylephrine to evoke contractions was greater in preparations from obese TET+/- mice ( pD 2 6.71±0.07 vs. lean TET+/- 6.34±0.13, n =5-6, P <0.05), whereas there was no change in the contractile response to the α 1 -adrenergic agonist by diet-induced obesity in WT littermates. The augmented EDCF responses to acetylcholine of quiescent carotid arterial rings of obese animals were further potentiated by TET+/- ( E max 51.3±1.1% vs. 40.6±1.3% KCl in WT obese, n =6, P <0.001). The production of 6-keto PGF 1α − the stable metabolite of prostacyclin − was increased significantly in preparations from obese TET+/- mice (238.4±30.0 vs. 127.0±12.7 pg/mL in obese WT littermates, n =4-6, P <0.05). In the presence of L-NAME, TP receptor activation by U46619 was more effective in obese TET+/- ( E max 151.8±5.4% vs. 126.1±4.7% KCl in WT obese, n =4-6, P <0.05). Overall, TET+/- had no effect on relaxations in obese animals, but contractile responses − EDCF-mediated ones in particular − were facilitated. The present results suggest that this is due to an increased production of vasoconstrictor prostanoids possibly combined with an augmented responsiveness of the underlying vascular smooth muscle.

Sign in / Sign up

Export Citation Format

Share Document