Mechanism of action of prostaglandin E2 in the dog skeletal muscle circulation.
OBJECTIVE
To determine whether prostaglandin E2 (PGE2) influences the dog skeletal muscle circulation by a direct action on the vascular smooth muscle or via pre- or post-synaptic modulation of sympathetic neurotransmission.


METHODS
In 18 anaesthetised dogs, a gracilis muscle was vascularly isolated and perfused at constant flow. Sympathetic vasoconstrictor tone on the muscles was reflexly controlled by alterations to the pressure at which the isolated carotid sinuses were perfused. The effects of PGE2 injection into the muscle were compared at low carotid sinus pressure, high carotid sinus pressure, and following denervation of the muscle, with or without noradrenaline infusion.


RESULTS
At all levels of sympathetic tone, PGE2 produced significantly more vasodilation than the saline vehicle. However, at a carotid sinus pressure of 46.0 +/- 2.3 mmHg (1 mmHg = 0.133 kPa), PGE2 caused a decrease in femoral arterial perfusion pressure of 52.6 +/- 7.1 mmHg, which was significantly greater than the response at a carotid sinus pressure of 208.5 +/- 3.7 (33.6 +/- 4.2 mmHg decrease) or following denervation (25.6 +/- 3.7 mmHg decrease). In a separate group of denervated muscles, PGE2 caused a similar decrease in perfusion pressure in the presence or absence of a noradrenaline infusion.


CONCLUSIONS
PGE2 appears to cause vasodilation through two separate mechanisms: one mechanism involves presynaptic inhibition of sympathetic vasoconstrictor tone, whilst the other is independent of the sympathetic nervous system, and is therefore presumably a direct action on the vascular smooth muscle or endothelium. Under our experimental conditions, both mechanisms contributed equally to the vasodilation.
Ballard
H J
HJ
Department of Physiology, University of Hong Kong, 5 Sassoon Road, Hong Kong, China.
Achike
F I
FI
D000818:Animals; D002346:Carotid Sinus / Q000187:drug effects; D015232:Dinoprostone / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D012039:Regional Blood Flow / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D014665:Vasodilator Agents; D015232:Dinoprostone