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A comparison of responses to raised extracellular potassium and endothelium-derived hyperpolarizing factor (EDHF) in rat pressurised mesenteric arteries.

Mathewson AM, Dunn WR - PLoS ONE (2014)

Bottom Line: The effects of barium and oubain, or capsaicin, on responses to raised extracellular potassium or ACh were also determined.The effects of raised extracellular potassium levels and ACh on membrane potential, were measured using sharp microelectrodes in pressurised arteries.ACh caused a substantial hyperpolarisation in pressurized arteries, while raising extracellular potassium did not.

View Article: PubMed Central - PubMed

Affiliation: Pharmacology Research Group, School of Life Sciences, University of Nottingham, Nottingham, United Kingdom.

ABSTRACT
The present study examined the hypothesis that potassium ions act as an endothelium-derived hyperpolarizing factor (EDHF) released in response to ACh in small mesenteric arteries displaying myogenic tone. Small mesenteric arteries isolated from rats were set up in a pressure myograph at either 60 or 90 mmHg. After developing myogenic tone, responses to raising extracellular potassium were compared to those obtained with ACh (in the presence of nitric oxide synthase and cyclo-oxygenase inhibitors). The effects of barium and oubain, or capsaicin, on responses to raised extracellular potassium or ACh were also determined. The effects of raised extracellular potassium levels and ACh on membrane potential, were measured using sharp microelectrodes in pressurised arteries. Rat small mesenteric arteries developed myogenic tone when pressurised. On the background of vascular tone set by a physiological stimulus (i.e pressure), ACh fully dilated the small arteries in a concentration-dependent manner. This response was relatively insensitive to the combination of barium and ouabain, and insensitive to capsaicin. Raising extracellular potassium produced a more inconsistent and modest vasodilator response in pressurised small mesenteric arteries. Responses to raising extracellular potassium were sensitive to capsaicin, and the combination of barium and ouabain. ACh caused a substantial hyperpolarisation in pressurized arteries, while raising extracellular potassium did not. These data indicate that K+ is not the EDHF released in response to ACh in myogenically active rat mesenteric small arteries. Since the hyperpolarization produced by ACh was sensitive to carbenoxolone, gap junctions are the likely mediator of EDH responses under physiological conditions.

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ACh produces a larger vasodilator response than raising extracellular potassium in myogenically-active mesenteric small arteries.Vasodilator responses to (A) ACh and (B) raised extracellular potassium in rat isolated mesenteric small arteries pressurised to 60 mmHg or 90 mmHg (in the presence of L-NAME and indomethacin). Following the development of stable myogenic tone, cumulative concentration response curves were constructed to ACh or potassium in random order in the same artery from n different animals. Each point represents the mean ± s.e.mean (n = 6–9).
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pone-0111977-g001: ACh produces a larger vasodilator response than raising extracellular potassium in myogenically-active mesenteric small arteries.Vasodilator responses to (A) ACh and (B) raised extracellular potassium in rat isolated mesenteric small arteries pressurised to 60 mmHg or 90 mmHg (in the presence of L-NAME and indomethacin). Following the development of stable myogenic tone, cumulative concentration response curves were constructed to ACh or potassium in random order in the same artery from n different animals. Each point represents the mean ± s.e.mean (n = 6–9).

Mentions: ACh, in the presence of combined inhibition of cyclo-oxygenase and nitric oxide synthase, produced concentration-dependent vasodilator responses in vessels displaying myogenic tone at both 60 and 90 mmHg (figure 1A), with a similar maximum response (Rmax: 97±2%, n = 7 (60 mmHg); 95±1%, n = 9 (90 mmHg)) and sensitivity (log EC50: −7.23±0.14; n = 7 (60 mmHg); −7.09±0.07; n = 9 (90 mmHg)). The vasodilator responses to raising extracellular potassium in mesenteric small arteries (figure 1B), despite being variable (Rmax: −1 to 96% maximum diameter), did not differ significantly when measured at either 60 or 90 mmHg (60 mmHg: 35±9% maximum relaxation; n = 6; compared to 90 mmHg: 49±9% maximum relaxation; n = 9). When comparing responses to ACh and potassium in the same vessel, vasodilator responses to ACh were greater in magnitude (range 60 mmHg: 92–100% maximum diameter and 90 mmHg: 82–100% maximum diameter) than responses to potassium (range 60 mmHg: −1–53% maximum diameter and 90 mmHg: 12–96% maximum diameter), regardless of the order in which they were applied.


A comparison of responses to raised extracellular potassium and endothelium-derived hyperpolarizing factor (EDHF) in rat pressurised mesenteric arteries.

Mathewson AM, Dunn WR - PLoS ONE (2014)

ACh produces a larger vasodilator response than raising extracellular potassium in myogenically-active mesenteric small arteries.Vasodilator responses to (A) ACh and (B) raised extracellular potassium in rat isolated mesenteric small arteries pressurised to 60 mmHg or 90 mmHg (in the presence of L-NAME and indomethacin). Following the development of stable myogenic tone, cumulative concentration response curves were constructed to ACh or potassium in random order in the same artery from n different animals. Each point represents the mean ± s.e.mean (n = 6–9).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4221422&req=5

pone-0111977-g001: ACh produces a larger vasodilator response than raising extracellular potassium in myogenically-active mesenteric small arteries.Vasodilator responses to (A) ACh and (B) raised extracellular potassium in rat isolated mesenteric small arteries pressurised to 60 mmHg or 90 mmHg (in the presence of L-NAME and indomethacin). Following the development of stable myogenic tone, cumulative concentration response curves were constructed to ACh or potassium in random order in the same artery from n different animals. Each point represents the mean ± s.e.mean (n = 6–9).
Mentions: ACh, in the presence of combined inhibition of cyclo-oxygenase and nitric oxide synthase, produced concentration-dependent vasodilator responses in vessels displaying myogenic tone at both 60 and 90 mmHg (figure 1A), with a similar maximum response (Rmax: 97±2%, n = 7 (60 mmHg); 95±1%, n = 9 (90 mmHg)) and sensitivity (log EC50: −7.23±0.14; n = 7 (60 mmHg); −7.09±0.07; n = 9 (90 mmHg)). The vasodilator responses to raising extracellular potassium in mesenteric small arteries (figure 1B), despite being variable (Rmax: −1 to 96% maximum diameter), did not differ significantly when measured at either 60 or 90 mmHg (60 mmHg: 35±9% maximum relaxation; n = 6; compared to 90 mmHg: 49±9% maximum relaxation; n = 9). When comparing responses to ACh and potassium in the same vessel, vasodilator responses to ACh were greater in magnitude (range 60 mmHg: 92–100% maximum diameter and 90 mmHg: 82–100% maximum diameter) than responses to potassium (range 60 mmHg: −1–53% maximum diameter and 90 mmHg: 12–96% maximum diameter), regardless of the order in which they were applied.

Bottom Line: The effects of barium and oubain, or capsaicin, on responses to raised extracellular potassium or ACh were also determined.The effects of raised extracellular potassium levels and ACh on membrane potential, were measured using sharp microelectrodes in pressurised arteries.ACh caused a substantial hyperpolarisation in pressurized arteries, while raising extracellular potassium did not.

View Article: PubMed Central - PubMed

Affiliation: Pharmacology Research Group, School of Life Sciences, University of Nottingham, Nottingham, United Kingdom.

ABSTRACT
The present study examined the hypothesis that potassium ions act as an endothelium-derived hyperpolarizing factor (EDHF) released in response to ACh in small mesenteric arteries displaying myogenic tone. Small mesenteric arteries isolated from rats were set up in a pressure myograph at either 60 or 90 mmHg. After developing myogenic tone, responses to raising extracellular potassium were compared to those obtained with ACh (in the presence of nitric oxide synthase and cyclo-oxygenase inhibitors). The effects of barium and oubain, or capsaicin, on responses to raised extracellular potassium or ACh were also determined. The effects of raised extracellular potassium levels and ACh on membrane potential, were measured using sharp microelectrodes in pressurised arteries. Rat small mesenteric arteries developed myogenic tone when pressurised. On the background of vascular tone set by a physiological stimulus (i.e pressure), ACh fully dilated the small arteries in a concentration-dependent manner. This response was relatively insensitive to the combination of barium and ouabain, and insensitive to capsaicin. Raising extracellular potassium produced a more inconsistent and modest vasodilator response in pressurised small mesenteric arteries. Responses to raising extracellular potassium were sensitive to capsaicin, and the combination of barium and ouabain. ACh caused a substantial hyperpolarisation in pressurized arteries, while raising extracellular potassium did not. These data indicate that K+ is not the EDHF released in response to ACh in myogenically active rat mesenteric small arteries. Since the hyperpolarization produced by ACh was sensitive to carbenoxolone, gap junctions are the likely mediator of EDH responses under physiological conditions.

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