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1.
Nacitarhan C Bayram Z Eksert B Usta C Golbasi I Ozdem SS 《Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy》2007,21(4):257-262
Introduction We investigated both the effect and the role(s) of potassium channels, nitric oxide (NO) and cyclooxygenase (COX) products
in the effect of hydrogen peroxide (H2O2) in human internal thoracic artery (ITA) rings.
Materials and methods Samples of redundant ITA obtained from patients undergoing a coronary artery bypass graft surgery were cut into 3 mm wide
rings and suspended in 20 ml organ baths. Isometric tension was continuously measured with an isometric force transducer connected
to a computer-based data acquisition system.
Results H2O2 (10−7–10−4 M) produced concentration-dependent relaxation responses in human ITA precontracted by phenylephrine. The relaxant responses
to H2O2 did not differ significantly between endothelium-intact and endothelium-denuded preparations. Incubation of human ITA rings
with superoxide dismutase (50 U/ml) did not affect the relaxant responses to H2O2, while 1,000 U/ml catalase caused a significant decrease. Incubation of endothelium-intact or endothelium-denuded human ITA
rings with voltage-dependent potassium channel blocker 4-aminopyridine (5 mM) significantly inhibited the relaxant responses
to H2O2. COX inhibitor indomethacin (10−5 M) also caused a significant inhibition. Incubation with ATP-dependent potassium channel blocker glibenclamide (10−6 M) or Ca2+-activated potassium channel blocker iberiotoxin (10−7 M) or NO synthase (NOS) blocker -nitro-l-arginine methyl ester (10−4 M) did not alter relaxant responses of ITA rings to H2O2.
Conclusion The findings of the present study suggested that H2O2-induced relaxation responses in human ITA were neither dependant on the endothelium nor blocked by NOS inhibition but they
rather seem to depend on the activation of voltage-dependent potassium channels and COX. 相似文献
2.
Akar F Manavbasi Y Parlar AI Ulus AT Katircioglu SF 《Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy》2007,21(5):331-338
Purpose The mechanism of the vasorelaxation to levosimendan varies depending on the vascular bed and species studied. Here, we examined
the vasorelaxation to levosimendan as well as its modification by various potassium channel antagonists in human internal
mammary artery (IMA) obtained from male and female patients.
Methods IMA grafts were supplied from 27 male and 19 age-matched female patients undergoing coronary bypass operation. The contraction
to noradrenaline and relaxation to levosimendan were studied in IMA rings obtained from both gender. The relaxations to levosimendan
were also assessed in the presence of glibenclamide (10 μM), an adenosine triphosphate-sensitive potassium channel (KATP) blocker, or charybdotoxin (100 nM), a calcium-activated potassium channel (KCa) blocker, or 4-aminopyridine(1 mM), a voltage-sensitive potassium channel (Kv) inhibitor.
Results Concentration–response curves to noradrenaline were not different in IMA rings from either gender. Pretreatment with levosimendan
(3 × 10−7 M) slightly modified the contractions to noradrenaline in both gender. Levosimendan (10−9–10−5 M) produced concentration-dependent relaxation in IMA rings, contracted by noradrenaline (5 × 10−6 M), from males and females. The vasodilatory effects of levosimendan were more pronounced in the arteries from males (83%)
than females (69%), in term of the maximal relaxation (E
max). Charybdotoxin and glibenclamide significantly inhibited the relaxation to levosimendan in the arteries from males but not
in those of females.
Conclusions The vasodilating efficacy of levosimendan and its relaxation mechanism differs between the arteries from males and females,
which may have clinical consequences in the treatment of heart failure. 相似文献
3.
Ethel C. Feleder MD Horacio A. Peredo Victoria E. Mendizábal Edda Adler-Graschinsky 《Age (Dordrecht, Netherlands)》1998,21(4):183-188
The aim of the present work was to evaluate, in the rat isolated mesenteric bed, whether increasing age is associated with
alterations in the ATP sensitive K+ channels functionality. Moreover, studies were performed in order to evaluate the effects of aging on the synthesis of vascular
prostanoids as well as on its possible contribution to the pressor responses of this vascular bed. Male Wistar rats of 3 month
(adults) and 24 month (aged) were used. Although no differences were found among adult and aged rats in pressor responses
to 2–30 nmol noradrenaline and to 40–160 nmol KCl, the relaxant responses to the K+ channel opener, 10−6 M cromakalim, were significantly diminished in the aged group compared to the adults. On the other hand, whereas PGF2α and 6-keto PGF1α production was not modified with age, the thromboxane B2 and prostaglandin E2 production in the mesenteric bed from 24 month old rats was significantly increased compared to the adult group. Furthermore,
the cyclooxigenase synthesis inhibitor, 10−5 M indomethacin reduced the pressor responses induced by noradrenaline in the mesenteric beds from adults but not from aged
rats. It is concluded that there is an age related reduction in the functionality of the ATP sensitive K+ channels in the rat mesenteric bed. In addition, aging produces an increase in the release of vasoconstrictor as well as
of vasodilator prostanoids, whose contribution to noradrenaline induced pressor responses appears to be less relevant in the
older animals. 相似文献
4.
We investigated the relaxant effects of forskolin, a diterpene derivative isolated from the roots ofColeus forskohlii, on guinea pig airway smooth muscle by measuring the isometric tension of tracheal smooth muscle in vitro and transcutaneous
Po2 during the histamine inhalation test (HIT) in vivo. Forskolin (10−9–10−5 M) caused dose-dependent relaxant effects on resting tone and on leukotriene C4 (10−7 M)-, leukotriene D4 (10−7 M)-, and carbachol (3 × 10−6 M)-induced contraction of tracheal smooth muscle. Moreover, with propranolol pretreatment the relaxant effect of forskolin
on tracheal smooth muscle did not change, whereas with the same pretreatment the relaxant effect of isoproterenol diminished.
Forskolin (10−8–10−6 M) raised tissue cyclic AMP levels dose-dependently in tracheal smooth muscle (6.7–359.9 pmol/mg protein). Forskolin (1 mg/kg)
administered subcutaneously raised the respiratory threshold of (RT-histamine in the HIT. The determination of the RT-histamine
by measuring tcPo2 was possible without anesthesia. These results suggest that forskolin relaxes airway smooth muscle in guinea pigs in vitro
and in vivo by raising tissue cyclic AMP levels and that its actions are independent ofβ-adrenoceptors. 相似文献
5.
Mitochondria regulate intracellular calcium (Ca2+) signals in smooth muscle cells, but mechanisms mediating these effects, and the functional relevance, are poorly understood. Similarly, antihypertensive ATP-sensitive potassium (KATP) channel openers (KCOs) activate plasma membrane KATP channels and depolarize mitochondria in several cell types, but the contribution of each of these mechanisms to vasodilation is unclear. Here, we show that cerebral artery smooth muscle cell mitochondria are most effectively depolarized by diazoxide (-15%, tetramethylrhodamine [TMRM]), less so by levcromakalim, and not depolarized by pinacidil. KCO-induced mitochondrial depolarization increased the generation of mitochondria-derived reactive oxygen species (ROS) that stimulated Ca2+ sparks and large-conductance Ca2+-activated potassium (KCa) channels, leading to transient KCa current activation. KCO-induced mitochondrial depolarization and transient KCa current activation were attenuated by 5-HD and glibenclamide, KATP channel blockers. MnTMPyP, an antioxidant, and Ca2+ spark and KCa channel blockers reduced diazoxide-induced vasodilations by >60%, but did not alter dilations induced by pinacidil, which did not elevate ROS. Data suggest diazoxide drives ROS generation by inducing a small mitochondrial depolarization, because nanomolar CCCP, a protonophore, similarly depolarized mitochondria, elevated ROS, and activated transient KCa currents. In contrast, micromolar CCCP, or rotenone, an electron transport chain blocker, induced a large mitochondrial depolarization (-84%, TMRM), reduced ROS, and inhibited transient KCa currents. In summary, data demonstrate that mitochondria-derived ROS dilate cerebral arteries by activating Ca2+ sparks, that some antihypertensive KCOs dilate by stimulating this pathway, and that small and large mitochondrial depolarizations lead to differential regulation of ROS and Ca2+ sparks. 相似文献
6.
To determine the site of action of inhaled nitric oxide (iNO) in the newborn pig lung, lungs were isolated and perfused at
constant flow for microfocal x-ray angiography. Measurements of pulmonary arterial diameters were made on arteries in the
100–2500 μm diameter range under control conditions, during vasoconstriction caused by hypoxia (decreasing PO2 from ∼120 to ∼50 Torr), or Nω-nitro-L-arginine methylester (L-NAME 10−4 M) administration, with or without vasodilation induced by iNO (40 ppm) or by the NO donor S-nitroso-N-acetylpenicillamine
(SNAP 5 × 10−6 M) given intravascularly. Hypoxia caused constriction only in smaller arteries whereas L-NAME constricted arteries throughout
the size range studied. iNO dilated the smaller arteries more than the larger arteries under all study conditions. SNAP was
used to provide an intravascular source of NO for comparison to iNO. SNAP also dilated smaller arteries more than larger arteries,
but it had a significantly greater effect on the large arteries than did iNO. This suggests that differential accessibility
of the vascular smooth muscle to NO between sources, air and blood, is a factor in the diameter dependence of the responses.
Accepted for publication: 13 March 2001 相似文献
7.
Ogawa Y Okumura K Matsui H Fukami Y Saburi Y Iami H Mizuno T Nishimoto Y 《Heart and vessels》2002,17(2):69-73
Nitroglycerin-mediated vasorelaxation is chiefly attributed to the cyclic guanosine monophosphate (cGMP)-dependent pathway,
and partly to the cGMP-independent pathway via calcium-activated K+ channels (KCa). To investigate whether chronic hypertension alters responses of vascular smooth muscle to vasoactive agonists, we determined
nitroglycerin-mediated relaxation of aortic rings from coarctation hypertensive rats. Banding the abdominal aorta above the
renal arteries for 4 weeks elevated blood pressure and caused cardiac hypertrophy by 49%. In response to nitroglycerin, the
relaxation of aortic rings precontracted with 10−7 M norepinephrine was lower in the banded group than in the sham-operated group. Methylene blue, a guanylate cyclase inhibitor,
suppressed a greater part of nitroglycerin-mediated relaxation and reached similar levels of relaxation in the two groups.
Charybdotoxin, a specific KCa channel blocker, also suppressed the relaxation by about 40% in the aortic rings from sham-operated animals, but not in those
from the banded group. The response to charybdotoxin was markedly diminished or virtually eliminated in the banded group in
the presence or absence of methylene blue. The combination of charybdotoxin and methylene blue nearly abolished nitroglycerin-mediated
relaxation in the sham-operated group, whereas nitroglycerin-mediated relaxation was seen to remain in the banded group. These
results indicate that the involvement of cGMP-independent KCa channels in nitroglycerin-mediated relaxation disappeared after the development of hypertension produced by aortic coarctation.
Received: May 20, 2002 / Accepted: July 27, 2002
Correspondence to K. Okumura 相似文献
8.
Growth hormone-releasing peptide-2 (GHRP-2) does not act via the human growth hormone-releasing factor receptor in GC cells 总被引:1,自引:0,他引:1
Chen Chen Paul Farnworth Stephan Petersenn Ian Musgrave Benedict J. Canny Iain J. Clarke 《Endocrine》1998,9(1):71-77
Effect of growth hormone-releasing peptide-2 (GHRP-2) on ovine somatotrophs is abolished by a growth hormone-releasing factor
(GRF) receptor antagonist, which raises the possibility that GHRP-2 may act on GRF receptors. In the present study, we used
rat pituitary GC cells with or without stable transfection of cDNA coding for the human GRF receptor (GC/R+ or GC/R−) to determine whether or not GHRP-2 acts via the GRF receptor. Northern blot analysis indicated that GRF receptor mRNA was
undetectable in GC/R− cells, whereas a high level of expression occurred in GC/R+ cells that were transfected by GRF receptor cDNA. In GC/R− cells, incubation with up to 10−7
M of either hGRF or GHRP-2 did not alter the intracellular cAMP, [Ca2+]i, or GH secretion. In GC/R+ cells, hGRF (10−11–10−7
M) increased cAMP levels in a concentration-dependent manner up to 20-fold. This increase in cAMP levels was blocked by a GRF
receptor antagonist, [Ac-Tyr1, d-Arg2]-GRF 1–29, but not by a Ca2+ channel blocker, NiCl2 (0.5 mM). GH secretion and [Ca2+]i were, however, not increased by hGRF. Incubation of the transfected cells with 10−11–10−8
M GHRP-2 did not modify intracellular cAMP levels. This result suggests that GHRP-2 does not act through the GRF receptor. 相似文献
9.
The mechanical response of guinea pig tracheal smooth muscle to leukotriene (LT) B4, C4, D4 and E4 was investigated, and the effects of several agents on LT-induced contraction were determined. Agents used in the present
study were: verapamil, a Ca-channel blocker; dibutyryl cyclic-AMP (DBcAMP); aminophylline; N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide
hydrochloride (W-7), a calmodulin antagonist; N-(6-aminohexyl)-1-naphthalene-sulfonamide hydrochloride (W-5), resembling W-7
in structure but without calmodulin antagonism. The results were as follows: 1) LTB4 had a contractile activity, dependent on the [Ca]o concentration; it was suppressed by a [Mg]o increase to 1.2 mM and over.
Little effect was observed from other drugs. 2) Contractile activities of LTC4, D4 and E4 were dose-dependent, depending upon [Ca]o as well as LTB4. 3) Verapamil (5×10−6−10−3 M), DBcAMP (3×10−6−3×10−3 M) and aminophylline (3×10−8−3×10−3 M) suppressed LTs (C4, D4, and E4, 10−8 M)-induced contraction dose-dependently. However, W-7 and W-5 did not suppress LT-induced contraction. These results suggest
that the LTC4-, D4-and E4-induced responses could be explained by the effect of LTC4, D4 and E4 on increasing Ca influx through the plasma membrane. 相似文献
10.
Role of nitric oxide in relaxation of the longitudinal layer of rectal smooth muscle 总被引:2,自引:2,他引:0
Mr. John F. Stebbing M.A. F.R.C.S. Alison F. Brading Ph.D. Neil J. McC Mortensen M.D. F.R.C.S. 《Diseases of the colon and rectum》1997,40(6):706-710
PURPOSE: This study was designed to investigate the role of nitric oxide in neurogenic relaxation of the longitudinal layer
of human rectal smooth muscle. METHODS: Tissue was obtained from the mid rectum of patients undergoing anterior resection
for carcinoma. Adjacent strips of longitudinal muscle were dissected and mounted in organ baths for isometric tension recording.
In preliminary experiments to determine the response of strips to cholinergic, adrenergic, and potential excitatory agonists,
strips were superfused with standard Krebs solution (37±0.5°C; pH, 7.4±0.05). Investigation of inhibitory, nonadrenergic noncholinergic
responses required the addition of 3×10−6 M histamine to induce reproducible and stable tension for five-minute “test” periods, during which electrical field stimulation
(EFS) and additional drugs were applied. In these experiments, strips were superfused with Krebs solution that contained atropine
sulfate (3×10−6 M) and guanethidine (3×10−6 M). RESULTS: The response to cholinergic and adrenergic agonists was typical of nonsphincter specialized gastrointestinal
smooth muscle. EFS elicited frequency-dependent, neurogenic (tetrodotoxin-sensitive) relaxations of precontracted strips,
which were reduced in dose-dependent fashion by addition ofNω-nitro-l-arginine and restored by addition of 3×10
−4
M
l-arginine but not by
d-arginine. Addition of exogenous nitric oxide (sodium nitroprusside) mimicked the relaxant response induced by EFS. CONCLUSION:
Smooth muscle from the longitudinal layer of human rectum receives an intrinsic inhibitory innervation mediated by nitric
oxide.
Supported and financed by the Medical Research Council, United Kingdom.
John Stebbing is in receipt of a Medical Research Council Clinical Training Fellowship.
Read at the meeting of The American Society of Colon and Rectal Surgeons, Seattle, Washington, June 9 to 14, 1996. 相似文献
11.
Summary In organ bath experiments, amphiphilic lipids lysophosphatidylcholine (LPC) and palmitylcarnitine (PLC) produced a small increase
in tension of nonprecontracted strips of porcine coronary artery with a subsequent decrease to initial level after high concentrations
of the agents, both in intact and endothelium-denuded preparations. Both amphiphiles produced dose-dependent but incomplete
relaxation of intact coronary strips precontracted with high potassium. The effect of PLC was more pronounced. LPC, 3 · 10−6 mol · l−1, did not influence Ca++-dose-response relationships, while PLC in concentration of 10−5 mol · l−1 abolished the decline in the second Ca++-dose-response curve. Neither PLC nor LPC in concentrations of 3 · 10−6 mol · l−1 influenced endothelium-dependent relaxation produced by bradykinin precontracted with high potassium porcine coronary artery.
Both amphiphiles did not change tension of nonprecontracted and precontracted with phenylephrine, 10−6 mol · l−1, rabbit femoral artery ring segments or Ca++-dose-response relationships with and without endothelium. 相似文献
12.
Kazuichi Okazaki Junko Kino Kensuke Suenaga Yasutake Yamamoto 《Journal of gastroenterology》1994,29(5):553-558
The effects of the muscarinic receptor agonist, carbamylcholine chloride (carbachol), on gastrin release and gastrin mRNA
levels in human antral mucosa (n=15) were determined. During a-2-h incubation period, carbachol (10−6−10−4M) decreased gastrin mRNA levels to 71±8% (10−6M), 40±8% (10−5M), and 33±5% (10−4M) of control levels. Carbachol (10−5M) decreased intracellular gastrin (from 1634±103 to 1272±126 pg/mg tissue protein), while it increased gastrin release into
the medium (from 609±48 to 918±68 pg/ml per mg tissue protein). After 6-and 9-h culture, carbachol gradually increased gastrin
mRNA levels, by 96±12% and 126±23%, respectively. Atropine sulfate (10−5 M) completely inhibited the carbachol-induced changes. Cycloheximide markedly decreased tissue gastrin concentration, but
increased gastrin mRNA levels, whereas it had no effects on gastrin release. These findings suggested that carbachol may have
a time-related biphasic action on human antral gastrin biosynthesis. 相似文献
13.
Hiroki Iida Mami Iida Motoyasu Takenaka Naokazu Fukuoka Shuji Dohi 《Journal of thrombosis and thrombolysis》2010,29(4):483-488
We previously reported that acute cigarette smoking can cause a dysfunction of endothelium-dependent vasodilation in cerebral
vessels, and that a reduction of oxidative stress by agents such as valsartan, fasudil, or apocynin prevented this impairment.
Here, our aim was to investigate the comparative effects of two antiplatelet drugs used for stroke-prevention [a phosphodiesterase-3
inhibitor (cilostazol) and a cyclooxygenase inhibitor (aspirin)] on smoking-induced endothelial dysfunction in cerebral arterioles.
In Sprague-Dawley rats, we used a closed cranial window preparation to measure the changes in pial vessel diameters induced
by topical application of acetylcholine (ACh) following intraperitoneal injection of 0.5% carboxymethyl cellulose sodium salt
(CMC; vehicle control for the antiplatelet drugs). After 1-min smoking (1 mg-nicotine cigarette), the arteriolar responses
to ACh were reexamined. Finally, after intraperitoneal cilostazol or aspirin (each in 0.5% CMC) pretreatment, we reexamined
the vasodilator responses to topical ACh (before and after cigarette smoking). Under control conditions, cerebral arterioles
were dose-relatedly dilated by topical ACh (10−6 and 10−5 M). One hour after 1-min smoking, 10−5 M ACh (a) constricted cerebral pial arterioles in the control group and in the aspirin-pretreatment group (responses not significantly
different from each other), but (b) dilated cerebral pial arteries in the cilostazol pretreatment groups (responses significantly
different from those obtained without cilostazol pretreatment). Thus, cilostazol (but not aspirin) may prevent the smoking-induced
impairment of endothelium-dependent vasodilation in cerebral pial arterioles. 相似文献
14.
Tian-Yi Yuan Yu Yan Yu-Jie Wu Xiao-Na Xu Li Li Xiao-Zhen Jiao Ping Xie Lian-Hua Fang Guan-Hua Du 《Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy》2014,28(5):415-424
Purpose
In the present study, we investigated the vasodilatory effect of a novel scaffold Rho-kinase inhibitor, DL0805-2, on isolated rat arterial rings including mesenteric, ventral tail, and renal arteries. We also examined the potential mechanisms of its vasodilatory action using mesenteric artery rings.Methods
A DMT multiwire myograph system was used to test the tension of isolated small arteries. Several drugs were employed to verify the underlying mechanisms.Results
DL0805-2 (10?7–10?4 M) inhibited KCl (60 mM)-induced vasoconstriction in three types of small artery rings (pEC50: 5.84?±?0.03, 5.39?±?0.03, and 5.67?±?0.02 for mesenteric, renal, and ventral tail artery rings, respectively). Pre-incubation with DL0805-2 (1, 3, or 10 μM) attenuated KCl (10–60 mM) and angiotensin II (AngII; 10?6 M)-induced vasoconstriction in mesenteric artery rings. The relaxant effect on the rat mesenteric artery was partially endothelium-dependent (pEC50: 6.02?±?0.05 for endothelium-intact and 5.72?±?0.06 for endothelium-denuded). The influx and release of Ca2+ were inhibited by DL0805-2. In addition, the increased phosphorylation levels of myosin light chain (MLC) and myosin-binding subunit of myosin phosphatase (MYPT1) induced by AngII were blocked by DL0805-2. However, DL0805-2 had little effect on K+ channels.Conclusions
The present results demonstrate that DL0805-2 has a vasorelaxant effect on isolated rat small arteries and may exert its action through the endothelium, Ca2+ channels, and the Rho/ROCK pathway. 相似文献15.
目的 在肺动脉平滑肌细胞(pulmonary arterial smooth muscle cells,PASMCs)上建立钙离子激活钾通道(calcium-activated potassium channel,KCa)电流、电压门控钾通道(voltage-gated potassium channel,Ky)电流和内向整流钾通道(Inward rectifier channel,Ku)电流的记录方法 .方法 用急性酶解的方法 分离出单个大鼠PASMC,利用全细胞膜片钳方法 记录钾电流.结果 ①急性酶解分离得到高质量的单个大鼠PASMC,呈梭形,边界清楚,胞浆均匀透亮.②Kv电流可以被5 mmol/L4-AP明显抑制,使电流-电压关系曲线明显下移,在55 mV时,Kv电流密度从(133.86±7.36)pA/pF减少到(59.09±3.35)pA/pF(n=6,P<0.05).③1 mmol/L TEA对KCa电流有明显抑制作用,使电流-电压关系曲线明显下移,在55 mV时,KCa电流密度从(9.03±1.42)pA/pF减少到(2.12±0.52)pA/pF(n=7,P<0.05).④KATP电流可以被10 μmol/L尼可地尔激活,使电流-电压关系曲线明显上移,在50 mV时,Kv电流密度从(29.08±5.90)pA/pF增加到(88.90±7.98)pA/pF(n=10,P<0.05).结论 在肺动脉平滑肌细胞上成功地建立了KCa、Kv和Kir电流的记录方法 ,可以为肺动脉相关疾病的发病机制和治疗方案的探索,提供有效的细胞模型基础. 相似文献
16.
OBJECTIVE : Localized release of Ca2+ from the sarcoplasmic reticulum (SR) toward the plasmalemma, sometimes visualized as Ca2+ sparks, can activate Ca2+-activated K+ (KCa) channels. We have already reported that the addition of charybdotoxin (ChTX), a blocker of KCa channels, to the resting state of arteries from spontaneously hypertensive rats (SHR) caused a powerful contraction, suggesting that KCa channels were active in the resting state. This study aimed to determine whether the Ca2+ responsible for activity of KCa channels was derived from SR. METHODS : Possible mechanisms underlying the ChTX-induced contractions were examined in endothelium-denuded strips of femoral, mesenteric, small mesenteric and carotid arteries from 13-week-old SHR and normotensive Wistar-Kyoto (WKY) rats by using selective inhibitors of the Ca2+ spark process. RESULTS : ChTX (100 nmol/l) induced a contraction in the SHR arteries. The ChTX-induced contractions were increased by a moderate membrane depolarization by 15.9 mmol/l K+ and were abolished by nifedipine (100 nmol/l). When SR Ca2+ was depleted by treatment of the strips with ryanodine (10 mumol/l) plus caffeine (20 mmol/l) or with thapsigargin (100 nmol/l), the ChTX-induced contraction was decreased in femoral, mesenteric and small mesenteric arteries and was almost abolished in the carotid artery. A similar phenomenon can be observed in arteries from WKY rats after a moderate membrane depolarization. In both SHR and WKY rats, SR Ca2+-dependent ChTX-induced contraction always represents 20-30% of the maximal K+-induced contraction. CONCLUSIONS : We conclude that activation of KCa channels depended upon influx of Ca2+ through L-type Ca2+ channels and release of Ca2+ from the SR, suggesting that recycling of entering Ca2+ from the superficial SR toward the plasmalemma sufficiently elevated Ca2+ near these channels to activate them. 相似文献
17.
Fibroblast growth factor-2, (FGF-2) and epidermal growth factor (EGF) are expressed in most tissues of the organism including
pituitary, FGF-2 increases PRL levels and PRL mRNA in GH3 cells and primary cultures, and it has been involved in the lactotroph
proliferation and hyperplasia. EGF also increases PRL levels in vitro. However, the effects of these two factors in the responses
of lactotroph cells to TRH and dopamine (DA) remain to be clarified. In the present work we have studied the modulator activity
of FGF-2 and EGF on in vitro PRL in responses to TRH and DA in primary cultures from in vivo vehicle-or estrogen (E2)-treated
rats. We have found that FGF-2 (2×10−11
M) prevents the EGF-induced dose-dependent increase in PRL levels in control cells, and reversed the EGF-stimulating effects
in cells from E2-treated rats. Both FGF-2 (2×10−11
M) and EGF (6.6×10−9
M) significantly increase (>30% and >120%, respectively) the PRL levels in response to TRH (10−6 10−5
M). FGF-2 blocked the inhibitory effects of low doses of DA (10−9
M). EGF was unable to do so, although markedly increased (>200%) the post-DA PRL rebound. In cells from in vivo E2-treated
rats, FGF-2 increased (>50%) the PRL secretion in response to TRH, while EGF reduced responses to high doses of TRH (10−6, 10−5
M). In addition, FGF-2 reversed and EGF increased the inhibitory effects of DA. Both FGF-2 and EGF completely blocked the post-DA
PRL rebound, in these cells. Taken together our data suggest that FGF-2 and EGF are important regulators of lactotroph responsiveness
to TRH and DA in vitro, although their actions are highly dependent on estrogenic milieu. 相似文献
18.
Furosemide-Induced Bronchodilation in the Rat Bronchus: Evidence of a Role for Prostaglandins 总被引:2,自引:0,他引:2
Pretreatment with inhaled fuorsemide has been shown to protect against bronchoconstrictive stimuli that indirectly activate
airway smooth muscle. However, it is controversial as to whether furosemide acts directly on airway smooth muscle. To investigate
this we studied the effect of furosemide on both methacholine (MCh)- and serotonin (5-HT)-induced bronchoconstriction in explanted
rat airways. Lungs from 21 Sprague-Dawley rats (269 ± 15 g) were excised, inflated with agarose solution at 37°C (1% w/v,
48 ml/kg), embedded in 4% agarose, and refrigerated to gel the agarose. Lung slices (0.5–1.0 mm thick) were cultured overnight
at 37°C. Explants were placed on a dissecting video microscope, and airway area was measured with an image analysis system.
MCh or 5-HT was administered directly to explanted airways (final concentrations 3.8 × 10−6 M and 3.8 × 10−5 M, respectively). Five min later furosemide (3.7 × 10−5 M or 3.7 × 10−4 M) was added and airway area monitored 5, 10, 15, 30, and 60 min later. Results were expressed as a percentage of the maximal
response. Significant bronchodilation was seen after 30 min in airways preconstricted with MCh and after 15 min in those preconstricted
with 5-HT following 3.7 × 10−4 M furosemide (p < 0.05). 3.7 × 10−5 M furosemide caused bronchodilation only at 60 min in airways constricted with 5-HT. The effect was blocked by a 30-min incubation
of explants with 10−6 M indomethacin. The furosemide-induced bronchodilation effect was not observed in airways strongly constricted with 3.8 ×
10−5 M MCh. These findings indicate that in the rat at least, furosemide induces a weak bronchodilator effect present only at
high doses, which seems to be dependent on the production of prostaglandins. This effect may be relevant to the observed therapeutic
action of furosemide in asthmatics.
Accepted for publication: 27 September 1996 相似文献
19.
Opening of ATP-sensitive potassium channels causes generation of free radicals in vascular smooth muscle cells 总被引:4,自引:2,他引:4
Krenz M Oldenburg O Wimpee H Cohen MV Garlid KD Critz SD Downey JM Benoit JN 《Basic research in cardiology》2002,97(5):365-373
Recent evidence suggests that opening of mitochondrial KATP channels in cardiac muscle triggers the preconditioning phenomenon through free radical production. The present study tested
the effects of KATP channel openers in a vascular smooth muscle cell model using the fluorescent probe MitoTracker (MTR) Red™ for detection of
reactive oxygen species (ROS). Rat aortic smooth muscle cells (A7r5) were incubated with 1 μM reduced MTR (non-fluorescent)
and the MTR oxidation product (fluorescent) was quantified. Thirty-minute pretreatment with either diazoxide (200 μM) or pinacidil
(100 μM), both potent mitochondrial KATP channel openers, increased fluorescent intensity (FI) to 149 and 162 % of control (p < 0.05 for both), respectively, and
the KATP channel inhibitor 5-hydroxydecanoate (5HD) blocked it. Valinomycin, a potassium-selective ionophore, raised FI to 156 % of
control (p <: 0.05). However, 5HD did not affect the valinomycin-induced increase in FI. Inhibition of mitochondrial electron
transport (myxothiazol) or uncoupling of oxidative phosphorylation (dinitrophenol) also blocked either valinomycin- or diazoxide-induced
increase in FI, and free radical scavengers prevented any diazoxide-mediated increase in fluorescence. Finally the diazoxide-induced
increase in fluorescence was not blocked by the PKC inhibitor chelerythrine, but was by HMR 1883, a putative surface KATP channel blocker. Thus opening of KATP channels increases generation of ROS via the mitochondrial electron transport chain in vascular smooth muscle cells. Furthermore,
a potassium-selective ionophore can mimic the effect of putative mitochondrial KATP channel openers. We conclude that potassium
movement through KATP directly leads to ROS production by the mitochondria.
Received: 7 January 2002, Returned for revision: 31 January 2002, Revision received: 21 February 2002, Accepted: 14 March
2002 相似文献
20.
Taiki Kida Kei Sawada Koji Kobayashi Masatoshi Hori Hiroshi Ozaki Takahisa Murata 《Heart and vessels》2014,29(3):390-395
Prostaglandin E2 (PGE2) is a major prostanoid produced under inflammatory situations. There have been controversial reports showing contractile or relaxant effect of PGE2 on vascular tone in various types of blood vessels. Thus, it is still elusive whether and how PGE2 modulates vascular tone. We here assessed the effects of PGE2 on vascular contractility using different types of vasculatures isolated form rat. In endothelium-denuded aortas and mesenteric arteries, PGE2 (1 nM–10 μM) concentration-dependently enhanced the contraction elicited by K+ (35.4 mM) or norepinephrine (10 nM). In pulmonary arteries, PGE2 did not alter the both-induced contraction. Tail arteries were relaxed by a low dose of PGE2 (1–100 nM), but this response shifted to contraction by the higher dose of PGE2 (300 nM–10 μM). There are four types of PGE2 receptors EP1-4. RT-PCR showed that aortas and mesenteric arteries abundantly expressed EP3, while tail arteries abundantly expressed EP4. We next revealed that selective EP3 agonism enhanced the contraction in mesenteric arteries, whereas EP4 agonism induced relaxation in tail arteries. Taken together, PGE2 causes different contractile responses depending on the type of vascular bed. This phenomenon may be due to the difference in expression pattern and activity of EP receptors. 相似文献