Role of Cl− currents in rat aortic smooth muscle activation by prostaglandin F2α

Jiang, Jihua; Backx, Peter H.; Teoh, Hwee; Ward, Michael E.

doi:10.1016/j.ejphar.2003.09.015

Cited by 3 publications

(2 citation statements)

References 34 publications

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“…14 The effects of the I Cl inhibitor (4,4Ј-diisothiocyanatostilbene-2,2Ј-disulfonic acid [DIDS]; 30 mol/L) on 5-bromodeoxyuridine (BrdUrd) incorporation and DNA content were assessed by flow cytometry as described previously. 15 Resting membrane potential (V m ) of rat PASMCs was measured using the whole-cell patch-clamp technique in current-clamp mode using the nystatin-perforated recording configuration 16 . In some studies, NMDG-HCl in the bath solution was reduced to 100 mmol/L (osmolarityϭ225 milliosmoles) to induce cell swelling.…”

Section: Methodsmentioning

confidence: 99%

Regulation of Proliferation and Membrane Potential by Chloride Currents in Rat Pulmonary Artery Smooth Muscle Cells

Liang

Ray

et al. 2009

Hypertension

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Abstract-Pulmonary artery smooth muscle cell (PASMC) proliferation contributes to increased pulmonary vascular resistance and pulmonary hypertension. Because proliferation depends on membrane potential (V m ) and because V m is, in part, determined by Cl Ϫ currents (I Cl ), we examined the effects of I Cl inhibition with 4,4Ј-diisothiocyanatostilbene-2,2Ј-disulfonic acid (DIDS) on cultured rat PASMCs. DIDS (30 mol/L) reduced cell numbers, decreased 5-bromodeoxyuridine incorporation and delayed cell cycle progression. I Cl inhibition with 5-Nitro-2-(3-phenylpropylamino) benzoic acid (100 mol/L) also reduced cell numbers of cultured rat PASMCs. To test the possible involvement of I Cl in the regulation of PASMC proliferation, we measured V m and I Cl in both cultured (proliferating) and acutely dissociated (nonproliferating) rat PASMCs. V m (Ϫ39.3Ϯ1.4 mV) was close to the equilibrium potential of Cl Ϫ (Ϫ39 mV) in proliferating PASMCs but differed from equilibrium potential of Cl Ϫ in acutely dissociated cells (Ϫ45.3Ϯ0.9 mV). DIDS and substitution of extracellular Cl Ϫ with I Ϫ induced V m hyperpolarization in proliferating but not nonproliferating PASMCs. Consistent with V m recordings, DIDS-sensitive baseline and swelling-activated (Ca 2ϩ -independent) I Cl s, recorded with low Ca 2ϩ (Ͻ1 nmol/L) pipette solutions, were Ϸ5-fold greater in proliferating than in nonproliferating PASMCs. By contrast, Ca 2ϩ -activated I Cl did not differ between proliferating and nonproliferating PASMCs. Ca 2ϩ -independent I Cl s were also increased in proliferating PASMCs acutely dissociated from rats exposed to hypoxia (10% O 2 ; 7 days). These findings are consistent with the conclusion that I Cl s regulate proliferation of PASMCs and suggest that selective I Cl inhibition may be useful in treating pulmonary hypertension. Key Words: Ca 2ϩ -independent chloride currents Ⅲ pulmonary hypertension Ⅲ hypoxia Ⅲ cell cycle Ⅲ phenotypic transition P ulmonary hypertension, uniformly fatal in its primary idiopathic form and a cause of premature mortality when it complicates cardiopulmonary disease, remains a difficult management problem. Pulmonary artery smooth muscle cell (SMC; PASMC) proliferation is a hallmark of the disease and contributes to increased vascular resistance to blood flow. 1,2 Understanding the mechanisms that regulate PASMC proliferation is necessary in order that new targets for therapeutic intervention may be identified.Swelling-activated chloride (Cl Ϫ ) currents (I Cl s) and Ca 2ϩ -activated I Cl s have been identified in PASMCs, 3,4 and PASMC expression of ClC-3, which is a candidate for mediation of swelling-activated I Cl 5 and is important for cell proliferation, 6,7 is upregulated in the pulmonary hypertensive rats. 8 Because of the transmembrane Cl Ϫ concentration gradients that exist in vascular smooth muscle, activation of Cl Ϫ channels causes Cl Ϫ efflux, cell volume decrease, 9 and plasma membrane depolarization. 10,11 Moreover, previous studies have identified that cytoplasmic volume must be adjusted duri...

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Section: Methodsmentioning

confidence: 99%

Regulation of Proliferation and Membrane Potential by Chloride Currents in Rat Pulmonary Artery Smooth Muscle Cells

Liang

Ray

et al. 2009

Hypertension

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“…Finally, the possibility that rhythmic contractions were being produced by the activation of the Cl − channels was considered in the experiments using NPPB, which selectively blocks these channels [54]. It has been shown in smooth muscle that Cl − channels can be stimulated by Ca 2+ influx through voltage‐gated channels.…”

Section: Discussionmentioning

confidence: 99%

Aortas Isolated from Sinoaortic‐Denervated Rats Exhibit Rhythmic Contractions That Are Regulated by Pharmacologically Distinct Calcium Sources

Rocha

Bendhack

2008

Basic Clin Pharma Tox

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Sinoaortic denervation is characterized by arterial pressure lability, without sustained hypertension. Aortas isolated from rats with sinoaortic denervation present rhythmic contractions. We studied the participation of distinct Ca 2+ sources in the maintenance of the oscillations. Three days after the surgeries, aortic rings were placed in an organ chamber, and the incidence of aortas presenting rhythmic contractions was measured. Specific drugs were employed to analyse the participation of the Ca 2+ released from the sarcoplasmic reticulum [2-APB (diphenylborinic acid 2-aminoethyl ester), thapsigargin and ryanodine] and external Ca 2+ entry [Bay K 8644, verapamil and DMB (dimethylbenzyl amiloride)] on the rhythmic contractions. Additionally, we verified the effects of chloride channel blocker NPPB [5-nitro-2-(3-phenylpropylamino)-benzoic acid] on the maintenance of the rhythmic contractions. Under phenylephrine stimulus, sinoaortic-denervated rat aortas exhibited rhythmic contractions in the frequency of 4.5 ± 0.50 cycles/min. and an amplitude of 0.465 ± 0.05 g. 2-APB, thapsigargin and ryanodine inhibited the rhythmic contractions. Bay K 8644 increased the oscillations, reaching maximum values with a concentration of 50 nM (18.5 ± 2.5 cycles/min.). The rhythmic contractions were inhibiting by verapamil and Ca 2+ -free solution. DMB and NPPB did not alter the oscillations. In conclusion, we observed that aorta isolated from sinoaortic-denervated rats present rhythmic contractions. Moreover, drugs that impaired intracellular Ca Cytosolic calcium concentration ([Ca 2+ ] c ) has a central role in controlling the vascular smooth muscle tone. The resting [Ca 2+ ] c in smooth muscle cells is around 100 nM [1,2]. In response to excitatory agonists, which produce InsP 3 , it increases by several hundredfold in a few minutes [3]. In the majority of cases, the increase in [Ca 2+ ] c can be attributed to Ca 2+ release from sarcoplasmic reticulum, which is considered to be the main cytosolic Ca 2+ store in vascular smooth muscle cells [4] and to Ca 2+ entry (via plasmalemmal Ca 2+ channels, pumps and exchangers) from the extracellular space [5].Smooth muscle is frequently classified by the manner in which it responds to excitatory stimulation. Therefore, tonic smooth muscle such as that often found in vasculature, airways, gastrointestinal and urogenital systems responds to contractile agonists by producing a simple steady contraction. In contrast, many previous studies have shown that some isolated smooth muscle preparations generate rhythmic contractions, as in the case of the rat portal vein [6], the subcutaneous artery of the dog [7], the bovine mesenteric vein [8], the rabbit urethra [9], the rat urinary bladder [10], the porcine thoracic duct [11] and bronquia [12], and many arteries from hypertensive rats [13][14][15][16].The effects of rhythmic contractions on the vascular beds are currently controversial and hence their physiological significance has yet to be correctly defined. In an atte...

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Pleiotropic Effects of Hydrogen Peroxide in Arteries and Veins From Normotensive and Hypertensive Rats

et al. 2006

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Hydrogen peroxide causes vascular contraction and relaxation and contributes to the pathogenesis of hypertension. We hypothesized that the contractile state of blood vessels governs whether H2O2 causes contraction or relaxation. Hydrogen peroxide (1 micromol/L to 1 mmol/L) concentration-dependently contracted thoracic aorta and vena cava from sham normotensive and deoxycorticosterone acetate (DOCA)-salt hypertensive rats. The maximal contraction to H2O2 was 3 times greater in DOCA aorta compared with sham aorta but unchanged in DOCA vena cava compared with sham vena cava. In prostaglandin F2alpha (20 micromol/L)-contracted aorta and vena cava from sham and DOCA rats, H2O2 (1 micromol/L to 1 mmol/L) induced a concentration-dependent relaxation that was impaired in DOCA aorta but not DOCA vena cava. In contrast, in KCl (30 mmol/L)-contracted vessels, maximal H2O2-induced contraction was enhanced 15-fold in sham aorta and 5-fold in DOCA aorta but only 2-fold in sham vena cava. Tetraethylammonium (10 mmol/L), BAY K 8644 (100 nmol/L), and ouabain (1 mmol/L) all enhanced maximal aortic H2O2-induced contraction, whereas only ouabain enhanced venous H2O2-induced contraction. The removal of extracellular Ca2+ reduced H2O2-induced contraction in KCl-contracted aorta, whereas maximal venous H2O2-induced contraction (under basal conditions) was unchanged. Our data suggest that differences in arterial and venous K+ channel activity and extracellular Ca2+ influx are responsible for differences in arterial and venous contraction to H2O2. In DOCA-salt hypertension, arterial but not venous contraction to H2O2 is enhanced, and relaxation to H2O2 is reduced.

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Role of Cl− currents in rat aortic smooth muscle activation by prostaglandin F2α

Cited by 3 publications

References 34 publications

Regulation of Proliferation and Membrane Potential by Chloride Currents in Rat Pulmonary Artery Smooth Muscle Cells

Regulation of Proliferation and Membrane Potential by Chloride Currents in Rat Pulmonary Artery Smooth Muscle Cells

Aortas Isolated from Sinoaortic‐Denervated Rats Exhibit Rhythmic Contractions That Are Regulated by Pharmacologically Distinct Calcium Sources

Pleiotropic Effects of Hydrogen Peroxide in Arteries and Veins From Normotensive and Hypertensive Rats

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