Endothelium-dependent inhibition of sympathetic vasoconstriction by frusemide administration to rats.
1. Segments of the tail artery of the rat were cannulated at both ends and mounted in an organ bath filled with Krebs solution. 2. Using an extracorporeal circuit, blood was pumped at a constant 2 ml/min from the carotid artery of anaesthetized rats to perfuse the segment of tail artery and returned to the donor rat via the jugular vein. 3. Peri-arterial electrical stimulation of the ex vivo blood perfused tail artery at 5 Hz produced vasoconstriction and an increase in perfusion pressure. 4. The intravenous administration of frusemide 5 mg/kg to the donor rat resulted in an inhibition of the vasoconstrictor responses of the perfused tail artery segment. Diuresis-induced losses of volume and frusemide were prevented by a urinary bladder-venous shunt. 5. Removal of the endothelium from the tail artery segment, by perfusion with dry gas for 4 min, prevented the vasoconstrictor-inhibitory effect of frusemide administration. Removal of the endothelium was confirmed histologically and by the absence of a vasodilator response to acetylcholine. 6. On the basis of these and previous results it is concluded that parenteral frusemide administration releases an unidentified but non-prostanoid hormone from the kidney which produces an endothelium-dependent inhibition of sympathetic vasoconstriction.
Gerkens
J F
JF
Discipline of Clinical Pharmacology, University of Newcastle, New South Wales, Australia.
Armsworth
S J
SJ
Dosen
P J
PJ
Smith
A J
AJ
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000033:anatomy & histology / Q000187:drug effects; D015232:Dinoprostone / Q000494:pharmacology; D004558:Electric Stimulation; D004730:Endothelium, Vascular / Q000502:physiology*; D005665:Furosemide / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000033:anatomy & histology / Q000187:drug effects*; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D013564:Sympathetic Nervous System / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects*
D005665:Furosemide; D015232:Dinoprostone; D000109:Acetylcholine