Endothelin-1-mediated vasoconstriction at rest and during dynamic exercise in healthy humans.
It is now generally accepted that alpha-adrenoreceptor-mediated vasoconstriction is attenuated during exercise, but the efficacy of nonadrenergic vasoconstrictor pathways during exercise remains unclear. Thus, in eight young (23 +/- 1 yr), healthy volunteers, we contrasted changes in leg blood flow (ultrasound Doppler) before and during intra-arterial infusion of the alpha(1)-adrenoreceptor agonist phenylephrine (PE) with that of the nonadrenergic endothelin A (ET(A))/ET(B) receptor agonist ET-1. Heart rate, arterial blood pressure, common femoral artery diameter, and mean blood velocity were measured at rest and during knee-extensor exercise at 20%, 40%, and 60% of maximal work rate (WR(max)). Drug infusion rates were adjusted for blood flow to maintain comparable doses across all subjects and conditions. At rest, PE infusion (8 ng x ml(-1) x min(-1)) provoked a rapid and significant decrease in leg blood flow (-51 +/- 3%) within 2.5 min. Resting ET-1 infusion (40 pg x ml(-1) x min(-1)) significantly decreased leg blood flow within 5 min, reaching a maximal vasoconstriction (-34 +/- 3%) after 25-30 min of continuous infusion. Compared with rest, an exercise intensity-dependent attenuation to PE-mediated vasoconstriction was observed (-18 +/- 5%, -7 +/- 2%, and -1 +/- 3% change in leg blood flow at 20%, 40%, and 60% of WR(max), respectively). Vasoconstriction in response to ET-1 was also blunted in an exercise intensity-dependent manner (-13 +/- 3%, -7 +/- 4%, and 2 +/- 3% change in leg blood flow at 20%, 40%, and 60% of WR(max), respectively). These findings support a significant contribution of ET-1 and alpha-adrenergic receptors in the regulation of skeletal muscle blood flow in the human leg at rest and suggest a similar, intensity-dependent "lysis" of peripheral ET and alpha-adrenergic vasoconstriction during dynamic exercise.
Wray
D Walter
DW
Dept. of Medicine, 9500 Gilman Dr., Univ. of California San Diego, La Jolla, CA 92093-0623, USA. dwray@ucsd.edu
Nishiyama
Steven K
SK
Donato
Anthony J
AJ
Sander
Mikael
M
Wagner
Peter D
PD
Richardson
Russell S
RS
D058646:Adrenergic alpha-1 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000328:Adult; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D019332:Endothelin-1 / Q000008:administration & dosage / Q000378:metabolism*; D015444:Exercise / Q000502:physiology*; D005260:Female; D005263:Femoral Artery / Q000187:drug effects / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007261:Infusions, Intra-Arterial; D017078:Laser-Doppler Flowmetry; D007866:Leg; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply*; D010656:Phenylephrine / Q000008:administration & dosage / Q000494:pharmacology*; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D017466:Receptors, Endothelin / Q000819:agonists / Q000378:metabolism; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology
D058646:Adrenergic alpha-1 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D019332:Endothelin-1; D018340:Receptors, Adrenergic, alpha-1; D017466:Receptors, Endothelin; D014662:Vasoconstrictor Agents; D010656:Phenylephrine