Single stretch-activated ion channels in vascular endothelial cells as mechanotransducers?

Lansman, Jeffry B.; Hallam, Trevor J.; Rink, T J

doi:10.1038/325811a0

Cited by 670 publications

(259 citation statements)

References 20 publications

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“…Since the reversal potential is near OmV in normal solutions ( Figure 3a), it appears that the channel displays poor selectivity for cations and thus Ca may permeate. A similar, presumably small permeability for Ca via nonspecific cation channels activated by stretch (Lansman et al, 1987) and thrombin or bradykinin Johns et al, 1987) has been recently reported in other cultured endothelial cells. On the other hand, the blocking action of internal Na for outward currents (Figure 3a) suggests that these channels display properties closer to those of other K-selective channels.…”

Section: Discussionmentioning

confidence: 95%

Histamine‐induced inward currents in cultured endothelial cells from human umbilical vein

Bregestovski

Bakhramov

Danilov

et al. 1988

British J Pharmacology

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1 The membrane response to applied histamine of cultured endothelial cells from human umbilical vein was studied by use of whole cell and single channel patch clamp techniques. A value of -27 + 1.4 mV was found for the resting potential under whole cell current clamp. No voltage-gated currents were seen at either the macroscopic or single channel levels. 2 At holding potentials of -20 to -40 mV, histamine evoked slow rising, long lasting whole cell inward currents. The inward current was associated with depolarization and decreased input resistance. The calcium ionophore A23187 provoked similar whole cell inward currents. 3 Single channel currents were observed in cell-attached and inside-out patches for both histamine and A23187. The single channel conductance was about 20 pS with a mean open time of 5 ms and a reversal potential of OmV in symmetrical potassium solutions. Internal sodium blocked outward going currents. 4 For cell-attached patches, histamine-dependent channel activity required external calcium and was also seen when histamine was present in the bath but not the pipette. Recording from insideout patches revealed that decreases in 'internal' calcium resulted in the disappearance of channel activity. 5 The histamine-dependent inward current appears to involve calcium-dependent activation of cationic channels.

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Section: Discussionmentioning

confidence: 95%

Histamine‐induced inward currents in cultured endothelial cells from human umbilical vein

Bregestovski

Bakhramov

Danilov

et al. 1988

British J Pharmacology

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“…Of interest, ␤ 1 -integrins are associated with caveolae within which caveolin and signaling complexes regulate the activity of endothelial NO synthase (15,25,35,38). Direct or indirect activation of ion channel activity has also been implicated as an endothelial mechanosensor (1,3,8,16,18,19,43). Taken together, myriad signaling pathways could account for the observed DVR endothelial response to luminal pressure.…”

Section: Discussionmentioning

confidence: 99%

Response of descending vasa recta to luminal pressure

Zhang¹,

Pallone²

2004

American Journal of Physiology-Renal Physiology

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Zhang, Zhong, and Thomas L. Pallone. Response of descending vasa recta to luminal pressure. Am J Physiol Renal Physiol 287: F535-F542, 2004. First published May 4, 2004 10.1152/ajprenal. 00394.2003.-We tested whether luminal perfusion and pressurization induce an endothelial cytoplasmic Ca 2ϩ ([Ca 2ϩ ]CYT) response in descending vasa recta (DVR). DVR isolated from the rat outer medulla were cannulated and subjected to free-flow microperfusion (5 nl/min); the onset of which increased [Ca 2ϩ ]CYT from a baseline of 76 Ϯ 13 to 221 Ϯ 65 nM. A graded increase in luminal pressure from 0 to 45 mmHg in stopped-flow experiments induced a parallel increase in [Ca 2ϩ ]CYT from a baseline of 74 Ϯ 24 to 194 Ϯ 33 nM at 45 mmHg, with a tendency for [Ca 2ϩ ]CYT to plateau at pressures Ͼ25 mmHg. The removal of extracellular Ca 2ϩ and blockade by either La 3ϩ (10 M) or SKF-96365 (100 M) eliminated the response. Luminal pressurization to 25 mmHg increased nitric oxide (NO) generation, a response blocked by NO synthase inhibition or removal of extracellular Ca 2ϩ . The NO generation was not affected by the superoxide dismutase mimetic tempol. We conclude that DVR endothelia are mechanosensitive and respond to luminal pressure by elevating [Ca 2ϩ ]CYT and generating NO. That response might augment medullary perfusion and saliuresis. medulla; kidney; microcirculation; shear; fura 2; 4,5-diaminofluoroscein DESCENDING VASA RECTA (DVR) are small generation resistance vessels that carry blood flow from the cortex to the medulla of the kidney. They originate as branches of the juxtamedullary efferent arteriole and traverse the outer medulla in vascular bundles to supply the inner and outer medulla. Their radial distribution within vascular bundles implies that they distribute and regulate regional blood flow within the medulla (34). DVR are lined with a continuous endothelium and enveloped by smooth muscle/pericytes that impart contractility (30,33). The importance of endothelial secretion of paracrine mediators to modulate adjacent smooth muscle is well established. Motivated by the importance of nitric oxide (NO) secretion in the maintenance of renal medullary perfusion and blood pressure (7,22,23,28) we employed microperfusion and fluorescence microscopy to test whether DVR endothelial cytoplasmic Ca 2ϩ ([Ca 2ϩ ] CYT ) is affected by the transmural pressure gradient imposed across the DVR wall. We exploited the property of the Ca 2ϩ -sensitive probe, fura 2, to preferentially load into DVR endothelia (while sparing pericytes) to quantify the effect of raising intraluminal pressure on [Ca 2ϩ ] CYT . In addition, the probe 4,5-diaminofluorescein (DAF-2), which increases fluorescence when covalently modified by NO, was used to monitor NO generation. The results verify that an increase in luminal pressure is accompanied by a parallel rise in DVR endothelial [Ca 2ϩ ] CYT and a robust increase in NO synthesis.NO functions as a vasodilator and "endogenous diuretic" (23, 28). We hypothesize that the vasa recta endothelium might serve a...

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“…With coronary perfusion pressures below 100 cm H 2 O, coronary vessels become maximally dilated and flow becomes pressure dependent 7 ; that is, autoregulation of coronary blood flow is lost 7 and control resides mainly in the endothelium of the vascular bed. An increase in coronary perfusion pressure results in an increase in water and cation content of endothelial cells, 2 which leads to stretch of endothelial cells and an elevation in coronary flow. 2 Vasodilators have little effect at the low perfusion pressure, but augment flow in the region of autoregulation in the isolated perfused heart, 8 including that of spontaneously hypertensive rats (SHR).…”

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confidence: 99%

“…An increase in coronary perfusion pressure results in an increase in water and cation content of endothelial cells, 2 which leads to stretch of endothelial cells and an elevation in coronary flow. 2 Vasodilators have little effect at the low perfusion pressure, but augment flow in the region of autoregulation in the isolated perfused heart, 8 including that of spontaneously hypertensive rats (SHR). "…”

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Effects of perfusion pressure on energy and work of isolated rat hearts.

Watters

Wikman‐Coffelt

et al. 1989

Hypertension

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A chemomechanical study of hypertrophied hearts of 6-month-old spontaneously hypertensive rats (SHR) and that of age-matched Wistar-Kyoto (WKY) rats was carried out, analyzing the response of the heart to steady-state changes in coronary perfusion pressure. The ratio of heart (dry)-to-body (wet) weight of WKY rats was 0.37±0.02 (10 3 ) and for SHR was 0.58±0.03 (1(T 3 ) (/7<0.01). In the apex-ejecting, isolated, pyruvate-perfused working hearts of WKY rats and SHR, coronary flow was constant when coronary perfusion pressure was set between 140 and 190 cm H 2 O (range of autoregulation). Coronary flow was perfusion pressure dependent when the coronary perfusion pressure was set below 110 cm H 2 O for both WKY rats and SHR. Cardiac output, developed pressure, rate of pressure development (dP/dt), and oxygen consumption were constant in the range of autoregulation but decreased in the direction of coronary flow when coronary flow was reduced by a drop in perfusion pressure. Similarly, the phosphorylation potential, phosphocreatine, adenosine triphosphate, and cyclic adenosine monophosphate were constant in the range of autoregulation but decreased directionally with coronary perfusion pressure below 110 cm H 2 O for both SHR and WKY rats. There was a significantly lower phosphorylation potential in SHR as compared with WKY rats when coronary perfusion pressure was reduced to 80 cm H 2 O. In the region of autoregulation, coronary flow and oxygen consumption were significantly less in SHR, although developed pressure was significantly greater at both high and low workloads. The importance of coronary perfusion pressure in SHR using the apex-ejecting working heart model was confirmed using other isolated perfused heart models (i.e., the Langendorff apex-vented heart model to simulate low workloads and the Langendorff isovolumic heart model to simulate high workloads). Furthermore, findings were not changed if FC-43 was added to the perfusate to facilitate delivery of oxygen to the myocardium and increase the viscosity of the perfusate. (Hypertension 1989;13:480-488) C oronary flow depends on perfusion pressure and vascular resistance.'-7 Vascular resistance depends on neurohormonal factors, myocardial contraction, myocardial metabolites, partial gas pressure, and alterations in the vascular endothelium. '-10 Both in situ 7 and in the isolated perfused heart 8 there is a range of coronary perfusion pressures from about 100 to 180 cm H 2 O 7 -8 where coronary perfusion pressure does not influence coronary flow; however, with values lower than 100 cm H 2 O, alterations in perfusion pressure result in a direct correlation between coronary flow

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Single stretch-activated ion channels in vascular endothelial cells as mechanotransducers?

Cited by 670 publications

References 20 publications

Histamine‐induced inward currents in cultured endothelial cells from human umbilical vein

Histamine‐induced inward currents in cultured endothelial cells from human umbilical vein

Response of descending vasa recta to luminal pressure

Effects of perfusion pressure on energy and work of isolated rat hearts.

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