Cellular mechanisms underlying cutaneous pressure-induced vasodilation: in vivo involvement of potassium channels

Abstract

In the skin of humans and rodents, local pressure induces localized cutaneous vasodilation, which may be protective against pressure-induced microvascular dysfunction and lesion formation. Once activated by the local pressure application, capsaicin-sensitive nerve fibers release neuropeptides that act on the endothelium to synthesize and release nitric oxide (NO) and prostaglandins, leading to the development of the cutaneous pressure-induced vasodilation (PIV). The present study was undertaken to test in vivo the hypothesis that PIV is mediated or modulated by differential activation of K+ channels in anesthetized rats using pharmacological methods. Local pressure was applied at 11.1 Pa/s. Endothelium-independent and -dependent vasodilation were tested using iontophoretic delivery of sodium nitroprusside (SNP) and acetylcholine (ACh), respectively, and was correlated with PIV response. PIV was reduced after systemic administration of tetraethylammonium (a nonspecific K+ channel blocker), iberiotoxin [a specific large-conductance Ca2+-activated K+ (BKCa) channel blocker], and glibenclamide [a specific ATP-sensitive K+ (KATP) channel blocker], whereas PIV was unchanged by apamin (a specific small-conductance Ca2+-activated K+ channel blocker) and 4-aminopyridine (a specific voltage-sensitive K+ channel blocker). The responses to SNP and ACh were reduced by iberiotoxin but were unchanged by glibenclamide. We conclude that the cellular mechanism of PIV in skin involves BKCa and KATP channels. We suggest that the opening of BKCa and KATP channels contributes to the hyperpolarization of vascular smooth muscle cells to produce PIV development mainly via the NO and prostaglandin pathways, respectively.

Preventing pressure ulcers by assessment of the microcirculation in tissue exposed to pressure

“…However, the decrease in blood flow is of the greatest importance in this thesis, and in cases where a decrease in blood flow is detected this decrease is most certainly of physiological origin even if the true value might be even lower if not for the contribution from compression. One may speculate if there is a similar contribution due to compression in the LDF signal, but Fromy et al have shown that PIV can be blocked by drugs locally injected in the tissue (Fromy et al, 2000) or by iontophores (Garry et al, 2005). If the signal had a contribution due to compression, the blood flow signal monitored in these studies still would have shown an increase.…”

“…It was demonstrated that a pressure of at least 120 mmHg is required for blood flow cessation in healthy seated individuals while 20-30 mmHg is sometimes enough to generate the same response in geriatric hospital patients (Bennett et al, 1981). The experimental studies of Fromy and colleagues on PIV explored the response by applying progressively greater pressures (Abraham et al, 2001, Garry et al, 2005, Gaubert et al, 2007, and in young individuals the maximal PIV response in the finger was seen at 31.5 ± 2.3 mmHg (at a rate of pressure increase of 0.08 mmHg/s) (Fromy et al, 2010) and at 37.5 ± 20 mmHg (at a rate of pressure increase of 5 mmHg/s) (Fromy et al, 1998). Studies of the sacral tissue in healthy individuals showed a maximal PIV response at 25-50 mmHg with a further decrease in blood flow at greater pressure levels (Schubert and Fagrell, 1989).…”

KCa channels and epoxyeicosatrienoic acids: major contributors to thermal hyperaemia in human skin

“…KCa channels are involved in the cutaneous response to reactive hyperaemia, contributing approximately 45% of the hyperaemia (Lorenzo & Minson, 2007). Furthermore, BKCa channels are important in the cutaneous vasodilatory response to increases in external pressure (Garry et al 2005). Together, these findings indicate a key role of KCa channels in the skin microvasculature.…”

The Influence of Environmental Temperature on the Response of the Skin to Local Pressure: The Impact of Aging and Diabetes

“…Local pressure also causes a temporary increase in blood flow, known as a pressure-induced vasodilation (PIV), which causes a subsequent release of NO. 8 PIV is a natural protective mechanism, allowing the skin blood flow to increase temporarily after local pressure is applied. 9,10 Endothelial dysfunction can reduce the body's ability to produce and=or respond to NO.…”