Inhibition of K_ATP channel activity augments baroreflex‐mediated vasoconstriction in exercising human skeletal muscle

Abstract

In the present investigation we examined the role of ATP-sensitive potassium (K ATP ) channel activity in modulating carotid baroreflex (CBR)-induced vasoconstriction in the vasculature of the leg. The CBR control of mean arterial pressure (MAP) and leg vascular conductance (LVC) was determined in seven subjects (25 ± 1 years, mean ± S.E.M.) using the variable-pressure neck collar technique at rest and during one-legged knee extension exercise. The oral ingestion of glyburide (5 mg) did not change mean arterial pressure (MAP) at rest (86 versus 89 mmHg, P > 0.05), but did appear to increase MAP during exercise (87 versus 92 mmHg, P = 0.053). However, the CBR-MAP function curves were similar at rest before and after glyburide ingestion. The CBR-mediated decrease in LVC observed at rest (∼39%) was attenuated during exercise in the exercising leg (∼15%, P < 0.05). Oral glyburide ingestion partially restored CBR-mediated vasoconstriction in the exercising leg (∼40% restoration, P < 0.05) compared to control exercise. These findings indicate that K ATP channel activity modulates sympathetic vasoconstriction in humans and may prove to be an important mechanism by which functional sympatholysis operates in humans during exercise.

Sympathetic nervous system contributes to the age-related impairment of flow-mediated dilation of the superficial femoral artery

“…Strenuous exercise does not singularly lead to local sympatholysis; several other mechanisms occur, such as the release of vasoactive substances (18). One may argue that synthesis of these substances explains the enhanced postexercise FMD in older men.…”

“…A maximal exercise bout was added to the experiments performed on day 1. It is well known that exercise leads to local changes in sympathetic activity of the active limbs during exercise, commonly referred to as functional sympatholysis (18). This physiologic phenomenon provides an optimal homeostasis for the exercising muscles without neglecting the vital organs.…”

Blockade of ATP-sensitive potassium channels prevents the attenuation of the exercise pressor reflex by tempol in rats with ligated femoral arteries

“…K ATP channels on vascular smooth muscle, in contrast to those on group III and IV afferents, appear to have an important function during exercise. Specifically, K ATP channels on vascular smooth muscle are responsible, at least in part, for sympatholysis in both rats (41) and humans (20). We note with interest that K ATP channels on vascular smooth muscle can be opened by metabolic by-products of contraction, such as adenosine (22) and prostaglandins (5), of which only the latter are capable of stimulating group III and IV afferents (31).…”

Neural Control of Vascular Function in Skeletal Muscle

“…In contrast to rodents and dogs, the ability of NO to exert a sympatholytic effect in humans has been observed in some (55), but not all (75,234) studies. Nonetheless, a role for muscular NO in regulation of the K ATP channels has been implicated as a possible contributing mechanism to this process in both rodents (281) and humans performing knee extensor exercise (157). Of note, pharmacological activation (168) and blockade (157) of K ATP channels provide experimental support that this channel in particular is involved in the sympatholytic effect in both mice and humans, respectively.…”