Angiotensin II facilitates sympathetic transmission in rat hind limb circulation.
We developed a novel method to stimulate the sympathetic innervation of the isolated, perfused rat hind limb to investigate whether a subpressor concentration of angiotensin II (Ang II) facilitates noradrenergic transmission in the vascular bed to skeletal muscle. We electrically stimulated the lumbar sympathetic trunk while perfusing the preparation with artificial medium. Seventy-five percent of the resulting frequency-dependent increases in perfusion pressure were mediated by alpha 1-adrenergic receptors. Ang II (10 nM) significantly enhanced the effects of nerve stimulation at 1 and 10 Hz (by 42% and 35%, respectively). At a supramaximal stimulation frequency (20 Hz), Ang II prolonged the duration of the response without changing the peak increase in pressure. The reuptake inhibitor cocaine did not influence the effects of Ang II at 1 and 10 Hz but blocked the effect at 20 Hz. To control for nonspecific synergism with norepinephrine, we compared Ang II with vasopressin. Both peptides potentiated the pressor response to exogenous norepinephrine; however, vasopressin did not change the pressor response to nerve stimulation at any frequency. We conclude that Ang II, but not vasopressin, facilitates noradrenergic transmission in skeletal muscle resistance vessels, independent of its direct vasoconstrictor activity. The neurovascular preparation we describe may be useful in addressing other hypotheses concerning sympathetic transmission in skeletal muscle resistance vessels.
Department of Medicine-Nephrology, University of Erlangen-Nürnberg, FRG.
K F
KF
Hilgers
R
R
Veelken
G
G
Rupprecht
P W
PW
Reeh
F C
FC
Luft
J F
JF
Mann
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D003042:Cocaine / Q000494:pharmacology; D004558:Electric Stimulation; D006614:Hindlimb / Q000098:blood supply / Q000294:innervation; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects*
D000804:Angiotensin II; D001127:Arginine Vasopressin; D003042:Cocaine; D009638:Norepinephrine