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

Alastair M Mathewson,William R Dunn

doi:10.1371/journal.pone.0111977

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.

Highlights

A number of factors are released from the vascular endothelium that act to modify vascular smooth muscle tone, including some which cause endothelium-derived hyperpolarisation (EDH)
Subsequent studies questioned the role of potassium as an endothelium-derived hyperpolarizing factor (EDHF) in rat mesenteric small arteries, largely on the basis of inconsistencies observed in the functional vasorelaxant responses produced by raising extracellular potassium in comparison to the EDHF released in response to ACh [6,7,8]
The results from the present study indicate that potassium ions do not act as the EDHF released in response to ACh in pressurised mesenteric small arteries displaying myogenic tone

Summary

Introduction

A number of factors are released from the vascular endothelium that act to modify vascular smooth muscle tone, including some which cause endothelium-derived hyperpolarisation (EDH). Subsequent studies questioned the role of potassium as an EDHF in rat mesenteric small arteries, largely on the basis of inconsistencies observed in the functional vasorelaxant responses produced by raising extracellular potassium in comparison to the EDHF released in response to ACh [6,7,8]. It has been shown that the depolarisation associated with phenylephrine-induced contractile responses evokes the release of potassium from vascular smooth muscle cells, via calcium-activated potassium channels (KCa) This leads to the accumulation of a ‘‘potassium cloud’’ around vascular myocytes, which increases background activation of Na+/K+ ATPase, reducing the scope for potassiuminduced hyperpolarisation and vasorelaxation [9,10]. These observations led to the proposal that the presence of potassium clouds in vasospastic arteries would substantially reduce the scope for potassium acting as an EDHF, but that with more moderate levels of smooth muscle activation potassium could have an important physiological role as an EDHF [10]

Methods

Results

Conclusion