title: Only weak vasorelaxant properties of loop diuretics in isolated resistance arteries from man, rat and guinea pig.
abstract: Besides their diuretic action, loop diuretics may induce a rapid vasodilator effect that contribute to their short-term therapeutic properties. We examined the effects of furosemide (10(-6)-10(-3) mol l(-1)) in comparison with bumetanide (10(-6)-10(-4) mol l(-1)) on isolated resistance arteries from rat and guinea pig mesentery and human subcutaneous fat, and investigated the mechanism of the acute direct vasorelaxant action on an isometric microvascular myograph. Both loop diuretics induced concentration-dependent relaxation of resistance vessels irrespective of membrane potential. The maximal effect of furosemide was greatest in rat and least in human arteries. Both diuretics caused a rightward shift in the concentration-response curve to extracellular Ca(2+). Incubation with indomethacin (2 x 10(-5) mol l(-1)) or mechanical removal of the endothelium did not inhibit the loop diuretic-induced relaxation. At high concentrations (10(-4)-10(-3) mol l(-1)) loop diuretics exert only weak direct relaxant effects on isolated human subcutaneous resistance arteries compared to the vasorelaxant effects in rat and guinea pig mesenteric vessels.
authors.affiliation: Department of Intensive Care Medicine (519), University Medical Center St. Radboud, PO Box 9101, 6500 HB Nijmegen, The Netherlands. p.pickkers@ic.umen.nl
authors.forename: Peter
authors.initials: P
authors.lastname: Pickkers
authors.forename: Frans G M
authors.initials: FG
authors.lastname: Russel
authors.forename: Theo
authors.initials: T
authors.lastname: Thien
authors.forename: Alun D
authors.initials: AD
authors.lastname: Hughes
authors.forename: Paul
authors.initials: P
authors.lastname: Smits
mesh_terms: D000818:Animals; D001158:Arteries / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D002034:Bumetanide / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D004232:Diuretics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D016232:Endothelins / Q000096:biosynthesis; D005665:Furosemide / Q000494:pharmacology*; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D009638:Norepinephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011453:Prostaglandins / Q000096:biosynthesis; D051381:Rats; D014655:Vascular Resistance; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014667:Vasopressins / Q000494:pharmacology
chemical_list: D004232:Diuretics; D016232:Endothelins; D011453:Prostaglandins; D014662:Vasoconstrictor Agents; D002034:Bumetanide; D014667:Vasopressins; D011189:Potassium Chloride; D005665:Furosemide; D002118:Calcium; D009638:Norepinephrine