Mechanisms of renal vasoconstriction following furosemide in conscious rats.
Regional hemodynamics following intravenous injection of furosemide were studied in conscious rats instrumented with Doppler flowprobes. Furosemide caused a dose-dependent acute (within 3 min) transient increase in renal resistance (RR) followed by a later generalized vasoconstriction in the renal, mesenteric and hindquarter (HQR) vascular bed. With in vitro experiments a possible direct effect of furosemide on renal artery segments was excluded. The acute rise in RR was partly (approximately 40%) attenuated by pretreatment with phentolamine or prazosin, but not prevented by renal denervation, volume repletion or pretreatment with captopril, losartan, indomethacin, aminophylline, nifedipine, or a vasopressin V1A-receptor-antagonist. However, the acute renal vasoconstriction was absent in water diuretic rats. The later vasoconstriction was blunted by captopril (RR+HQR), losartan (RR) and phentolamine (HQR) pretreatment. We conclude that the later generalized vasoconstriction following furosemide involves regional specific stimulation of angiotensin II and alpha-adrenoceptors. The mechanism of the acute renal vasoconstriction could not be fully determined. Because of its absence in water diuretic rats, its rapid onset, transient nature and relative insensitivity for pharmacological tools in euvolemic rats, the acute increase in RR following furosemide may be caused by cell swelling as a result from dissipation of the renal medullary gradient.
Janssen
B J
BJ
Department of Pharmacology, Cardiovascular Research Institute Maastricht, University of Limburg, Maastricht, The Netherlands.
Eerdmans
P H
PH
Smits
J F
JF
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology; D002752:Chlorthalidone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005665:Furosemide / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects; D019808:Losartan; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D012077:Renal Artery / Q000187:drug effects* / Q000502:physiology; D013777:Tetrazoles / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*
D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D005665:Furosemide; D002216:Captopril; D019808:Losartan; D002752:Chlorthalidone