Inhibitory effect of frusemide on sympathetic vasoconstrictor responses: dependence on a renal hormone and the vascular endothelium.
1. Mesenteric perfusion pressure was measured in the in situ mesentery perfused at a constant rate with blood drawn from the carotid artery of the same anaesthetized rat. Increases in perfusion pressure were produced by mesenteric periarterial electrical stimulation. These responses were measured before and 30 min after the administration of frusemide (5 mg/kg i.v.) to the rat. Loss of volume due to the frusemide-induced diuresis was prevented by a urinary bladder-venous extracorporeal circuit. 2. Responses to stimulation were reduced after frusemide and were not increased by the subsequent administration of indomethacin (2 mg/kg i.v.). This indomethacin treatment rapidly and completely prevented the fall in blood pressure produced by i.v. arachidonic acid. 3. In rats where the renal papilla had been ablated by treatment with bromoethylamine (200 mg/kg i.p.) 5 weeks previously, frusemide administration did not reduce sympathetic responses in the in situ blood-perfused mesentery. 4. A segment of rat tail artery, cannulated at both ends was mounted in an organ bath and perfused with blood withdrawn from, and returned to, an anaesthetized rat. Increases in perfusion pressure produced by periarterial electrical stimulation of this ex vivo blood perfused tail artery segment were reduced by frusemide administration to the anaesthetized rat. 5. When the endothelium was removed from the tail artery segment, frusemide administration did not lead to any reduction of vasoconstrictor responses. 6. Frusemide may lead to the release of a non-prostanoid hormone from the renal medulla which results in inhibition of peripheral sympathetic vasoconstrictor responses. The release of the hormone may involve intra-renal prostaglandins. The final antivasoconstrictor effect requires an intact vascular endothelium.
Gerkens
J F
JF
Discipline of Clinical Pharmacology, University of Newcastle, New South Wales, Australia.
D000818:Animals; D001158:Arteries; D001794:Blood Pressure / Q000187:drug effects; D004558:Electric Stimulation; D004730:Endothelium, Vascular / Q000502:physiology*; D005665:Furosemide / Q000494:pharmacology*; D066298:In Vitro Techniques; D007679:Kidney Medulla / Q000187:drug effects / Q000502:physiology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013564:Sympathetic Nervous System / Q000187:drug effects*; D013623:Tail; D014661:Vasoconstriction / Q000187:drug effects*
D005665:Furosemide