Effects of Changes in pH and <i>P</i><sub>CO2</sub> on Wall Tension in Isolated Rat Intrapulmonary Arteries

Sweeney, Michele; O’Regan, R. G.; McLoughlin, Paul

doi:10.1111/j.1469-445x.1999.01864.x

Cited by 15 publications

(13 citation statements)

References 24 publications

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“…Previous studies of normocapnic acidosis on intact lung or on pulmonary resistance in vivo have produced conflicting results (either a reduction, an increase or no effect on pulmonary vascular resistance -see Sweeney et al, 1999), while systemic vessels typically relax to normocapnic acidosis (rat cerebral artery - Peng et al (1998); rat carotid artery - Sweeney et al, 1999). The membrane potential (in the region of -40 mV in pulmonary arteries) observed in the presence of an acidic extracellular pH was close to the activation threshold of voltage-gated Ca 2 þ channels in arterial myocytes (Clapp & Gurney, 1991 (Peng et al, 1998), little or no change in tone would be anticipated on simply shifting extracellular pH from 7.4 to 6.4 in spite of the ensuing membrane depolarisation.…”

Section: Blood Vessel Tone: Involvement Of Task-1 and Task-2 Channelsmentioning

confidence: 99%

Functional evidence of a role for two‐pore domain potassium channels in rat mesenteric and pulmonary arteries

Gardener

Johnson

Burnham

et al. 2004

British J Pharmacology

129

123

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1 Experiments were performed to elucidate the mechanism by which alterations of extracellular pH (pH o ) change membrane potential (E M ) in rat mesenteric and pulmonary arteries. 2 Changing pH o from 7.4 to 6.4 or 8.4 produced a depolarisation or hyperpolarisation, respectively, in mesenteric and pulmonary arteries. Anandamide (10 mM) or bupivacaine (100 mM) reversed the hyperpolarisation associated with alkaline pH o , shifting the E M of both vessels to levels comparable to that at pH 6.4. In pulmonary arteries, clofilium (100 mM) caused a significant reversal of hyperpolarisation seen at pH 8.4 but was without effect at pH 7.4. 3 K þ channel blockade by 4-aminopyridine (4-AP) (5 mM), tetraethylammonium (TEA) (10 mM), Ba 2 þ (30 mM) and glibenclamide (10 mM) depolarised the pulmonary artery. However, shifts in E M with changes in pH o remained and were sensitive to anandamide (10 mM), bupivacaine (100 mM) or Zn 2 þ (200 mM). 4 Anandamide (0.3-60 mM) or bupivacaine (0.3-300 mM) caused a concentration-dependent increase in basal tone in pulmonary arteries. 5 RT-PCR demonstrated the expression of TASK-1, TASK-2, THIK-1, TRAAK, TREK-1, TWIK-1 and TWIK-2 in mesenteric arteries and TASK-1, TASK-2, THIK-1, TREK-2 and TWIK-2 in pulmonary arteries. TASK-1, TASK-2, TREK-1 and TWIK-2 protein was demonstrated in both arteries by immunostaining. 6 These experiments provide evidence for the presence of two-pore domain K þ channels in rat mesenteric and pulmonary arteries. Collectively, they strongly suggest that modulation of TASK-1 channels is most likely to have mediated the pH-induced changes in membrane potential observed in these vessels, and that blockade of these channels by anandamide or bupivacaine generates a small increase in pulmonary artery tone.

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Section: Blood Vessel Tone: Involvement Of Task-1 and Task-2 Channelsmentioning

confidence: 99%

Functional evidence of a role for two‐pore domain potassium channels in rat mesenteric and pulmonary arteries

Gardener

Johnson

Burnham

et al. 2004

British J Pharmacology

129

123

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“…Sweeney et al (40,41) reported that in the PA, normocapnic acidosis (NA) leads to an endothelium-independent relaxation of isolated PA, which is less than that observed in the aorta. These results suggest that in PA smooth muscle, tension development is relatively resistant to reduction in extracellular pH compared with systemic vascular smooth muscle and that this resistance is an intrinsic property of pulmonary arterial smooth muscle cells (PASMC).…”

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confidence: 99%

“…This resistance to acidosis plays an important role in ventilation-perfusion matching in the lung in such diseases, since a vasodilator response to hypercapnic acidosis would antagonize hypoxic vasoconstriction in poorly ventilated regions of the lung, thus diverting blood to these regions and impairing normal gas exchange. Sweeney et al (40,41) reported that in the PA, normocapnic acidosis (NA) leads to an endothelium-independent relaxation of isolated PA, which is less than that observed in the aorta. These results suggest that in PA smooth muscle, tension development is relatively resistant to reduction in extracellular pH compared with systemic vascular smooth muscle and that this resistance is an intrinsic property of pulmonary arterial smooth muscle cells (PASMC).…”

mentioning

confidence: 99%

“…In our laboratory previous observations have shown that the relative resistance of PA to acidosis was unaffected by removal of extracellular calcium or by inhibition of the voltage-operated Ca 2ϩ channels (Sweeney M and McLoughlin P, unpublished data). Moreover, Sweeney et al (41) reported that the PGF 2␣ -induced contraction that is largely mediated through sensitization of the contractile apparatus (17) was unaffected by acidosis. Together, these results suggest that the Ca 2ϩ sensitization pathway could be insensitive to acidosis and that a greater contribution of the RhoA/ Rho-kinase pathway in agonist-induced tension development in PA could account for this resistance.…”

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confidence: 99%

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Effect of changes in pH on wall tension in isolated rat pulmonary artery: role of the RhoA/Rho-kinase pathway

Hyvelin¹,

O’Connor²,

McLoughlin³

2004

American Journal of Physiology-Lung Cellular and Molecular Phys

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Hyvelin, Jean-Marc, Clare O'Connor, and Paul McLoughlin. Effect of changes in pH on wall tension in isolated rat pulmonary artery: role of the RhoA/Rho-kinase pathway. Am J Physiol Lung Cell Mol Physiol 287: L673-L684, 2004. First published February 6, 2004 10.1152/ajplung.00331.2003 are resistant to the vasodilator effects of extracellular acidosis in systemic vessels; the mechanism underlying this difference between systemic and pulmonary circulations has not been elucidated. We hypothesized that RhoA/Rho-kinase-mediated Ca 2ϩ sensitization pathway played a greater role in tension development in pulmonary than in systemic vascular smooth muscle and that this pathway was insensitive to acidosis. In arterial rings contracted with the ␣ 1-agonist phenylephrine (PE), the Rho-kinase inhibitor Y-27632 (Յ3 M) induced greater relaxation in precontracted PA rings than in aortic rings. In PA rings stimulated by PE, the activation of RhoA was greater than in aorta. Normocapnic acidosis (NA) induced a smaller relaxation in precontracted PA than in aorta. However, in the presence of nifedipine and thapsigargin, when PE-induced contraction was predominantly mediated by Rho-kinase, the relaxant effect of NA was reduced and similar in both vessel types. Furthermore, in the presence of Y-27632, NA induced a greater relaxation in both PA and aorta, which was similar in both vessels. Finally, in ␣-toxin-permeabilized smooth muscle, PE-induced contraction at constant Ca 2ϩ activity was inhibited by Y-27632 and unaffected by acidosis. These results indicate that Ca 2ϩ sensitization induced by the RhoA/Rho-kinase pathway played a greater role in agonist-induced vascular smooth muscle contraction in PA than in aorta and that tension mediated by this pathway was insensitive to acidosis. The predominant role of the RhoA/Rho-kinase pathway in the pulmonary vasculature may account for the resistance of this circulation to the vasodilator effect of acidosis observed in the systemic circulation. vascular smooth muscle; acidosis; RhoA; calcium sensitization; Y-27632 NORMAL GAS EXCHANGE in the lung depends on the appropriate regulation of pulmonary blood flow to ensure matching of regional blood flow to ventilation to provide better gas exchanges. Hypoxic pulmonary vasoconstriction (HPV) is one of the main functional properties of the pulmonary circulation, which enables this matching. A second functional specialization seen in the pulmonary circulation is a resistance to the vasodilator effect of extracellular acidosis (5) in contrast to the potent vasodilator effect of this stimulus in the systemic circulation (1). Reduction in pH and elevation of PCO 2 in pulmonary arterial (PA) blood is observed in acute and chronic lung diseases. This resistance to acidosis plays an important role in ventilation-perfusion matching in the lung in such diseases, since a vasodilator response to hypercapnic acidosis would antagonize hypoxic vasoconstriction in poorly ventilated regions of the lung, thus diverting blood to these regions and impairing norma...

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“…24 In brief, the rings were mounted on a Mulvaney-Halpern small vessel dual myograph (Model 410A, Linton Instrumentation, Norfolk, England) using two 40 mm intraluminal wires. 25 Isometric tension was recorded as a function of time using an analogue to digital system (Biopac MP100 WS, Linton Instrumentation, Norfolk, England) connected to a desktop computer (Apple Macintosh Performa 6200).…”

Section: Experimental Set-upmentioning

confidence: 99%

Role of cyclooxygenase and haemoxygenase products in nitric oxide-independent vasodilatation in the porcine ciliary artery

Quinn

O’Brien

McLoughlin

2003

Eye

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Purpose Vascular endothelial cell dysfunction has been noted in patients with normal pressure glaucoma. Although nitric oxide (NO) accounts for a large proportion of vasorelaxation in the posterior ciliary artery, considerable relaxation remains unexplained. We investigated the roles of haemoxygenase (HO) and cyclooxygenase (COX), which produce the vasodilators carbon monoxide (CO) and prostacyclin, respectively, in NO-independent endothelium-dependent vasodilatation in porcine posterior ciliary arteries. Methods Isolated vascular rings were mounted in a Mulvaney-Halpern small vessel myograph for the measurement of isometric tension development. Vasodilator responses to bradykinin (BK) were elicited in each ring on three separate occasions following preconstriction with prostaglandin F 2a : first in the absence of inhibitors, second in the presence of the NO synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME, 10 -3 M), and third in the presence of L-NAME and either a COX (indomethacin, 10 -6 M) or an HO inhibitor (tin protoporphyrin-IX 10 -5 M). Results were expressed as a percentage of the maximal relaxation in the presence of L-NAME alone.Results Incubation with indomethacin (n ¼ 6), in the presence of L-NAME, significantly reduced (Po0.01) maximum BK-induced relaxation (À103.578.8%) compared to paired rings in the presence of L-NAME alone (À130.878.8%). HO inhibition did not reduce NO-independent, BK-induced relaxation when compared to paired control vessels.Conclusions These data suggest that in the presence of L-NAME, a COX product accounts for a significant proportion of NO-independent vasodilatation. In contrast, endogenous CO production does not have a functionally significant role in the porcine ciliary artery.

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Effects of Changes in pH and P_CO2 on Wall Tension in Isolated Rat Intrapulmonary Arteries

Cited by 15 publications

References 24 publications

Functional evidence of a role for two‐pore domain potassium channels in rat mesenteric and pulmonary arteries

Functional evidence of a role for two‐pore domain potassium channels in rat mesenteric and pulmonary arteries

Effect of changes in pH on wall tension in isolated rat pulmonary artery: role of the RhoA/Rho-kinase pathway

Role of cyclooxygenase and haemoxygenase products in nitric oxide-independent vasodilatation in the porcine ciliary artery

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Effects of Changes in pH and PCO2 on Wall Tension in Isolated Rat Intrapulmonary Arteries

Cited by 15 publications

References 24 publications

Functional evidence of a role for two‐pore domain potassium channels in rat mesenteric and pulmonary arteries

Functional evidence of a role for two‐pore domain potassium channels in rat mesenteric and pulmonary arteries

Effect of changes in pH on wall tension in isolated rat pulmonary artery: role of the RhoA/Rho-kinase pathway

Role of cyclooxygenase and haemoxygenase products in nitric oxide-independent vasodilatation in the porcine ciliary artery

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Effects of Changes in pH and P_CO2 on Wall Tension in Isolated Rat Intrapulmonary Arteries