α1-Adrenergic responsiveness in human skeletal muscle feed arteries: the impact of reducing extracellular pH.
Graded exercise results not only in the modulation of adrenergic mediated smooth muscle tone and a preferential increase in blood flow to the active skeletal muscle termed 'functional sympatholysis', but is also paralleled by metabolically induced reductions in pH. We therefore sought to determine whether pH attenuates α(1)-adrenergic receptor sensitivity in human feed arteries. Feed arteries (560 ± 31 μm i.d.) were harvested from 24 humans (55 ± 4 years old) and studied using the isometric tension technique. Vessel function was assessed using KCl, phenylephrine (PE), ACh and sodium nitroprusside (SNP) concentration-response curves to characterize non-receptor-mediated and receptor-mediated vasocontraction, as well as endothelium-dependent and -independent vasorelaxation, respectively. All concentration-response curves were obtained from (originally contiguous) vessel rings in separate baths with a pH of 7.4, 7.1, 6.8 or 6.5. Reduction of the pH, via HCl, reduced maximal PE-induced vasocontraction (pH 7.4 = 85 ± 19, pH 7.1 = 57 ± 16, pH 6.8 = 34 ± 15 and pH 6.5 = 16 ± 5% KCl(max)), which was partly due to reduced smooth muscle function, as assessed by KCl (pH 7.4 = 88 ± 13, pH 7.1 = 67 ± 8, pH 6.8 = 67 ± 9 and pH 6.5 = 58 ± 8% KCl(max)). Graded acidosis had no effect on maximal vasorelaxation. In summary, these data reveal that reductions in extracellular pH attenuate α(1)-mediated vasocontraction, which is partly explained by reduced smooth muscle function, although vasorelaxation in response to ACh and SNP remained intact. These findings support the concept that local acidosis is likely to contribute to functional sympatholysis and exercise hyperaemia by opposing sympathetically mediated vasoconstriction while not impacting vasodilatation.
Geriatric Research, Education and Clinical Center, George E. Whalen VA Medical Center, Salt Lake City, UT, USA. stephen.ives@utah.edu
Stephen J
SJ
Ives
Robert H I
RH
Andtbacka
R Dirk
RD
Noyes
R Garrett
RG
Morgan
Jayson R
JR
Gifford
Song-Young
SY
Park
J David
JD
Symons
Russell S
RS
Richardson
D000138:Acidosis / Q000503:physiopathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001158:Arteries / Q000502:physiology*; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000098:blood supply*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D018340:Receptors, Adrenergic, alpha-1; D010656:Phenylephrine