Furosemide elicits immediate sympathoexcitation via a renal mechanism independent of angiotensin II.
This investigation aimed at examing the hypothesis that furosemide elicits renal sympathoexcitation through stimulation of renal renin release, which in turn produces increased plasma angiotensin II levels, causing centrally mediated sympathoexcitation. In addition, direct central nervous actions of furosemide on central control of mean arterial pressure, heart rate, and efferent renal sympathetic nerve activity were examined. Furosemide (300 mg/kg intravenously) was administered to four groups of rats: (1) control; (2) nephrectomized; (3) with intravenous losartan blockade (10 mumol/kg); and (4) with intracerebroventricular losartan blockade (10 nmol). In a fifth group of rats, furosemide was administered intracerebroventricularly (0, 2.5, 25 or 250 micrograms). To eliminate reflex control of mean arterial pressure, heart rate and efferent renal sympathetic nerve activity, all experiments were performed in rats with sinoaortic denervation and bilateral vagotomy. Experiments were performed during Saffan anaesthesia (0.9% alphaxalone/0.3% alphadolone), and rats were paralyzed with pancuronium and artifically ventilated. Furosemide produced an immediate 40% increase in efferent renal sympathetic nerve activity while the furosemide vehicle, 2 vol.% ethanolamine, did not affect efferent renal sympathetic nerve activity. The furosemide-induced increase in efferent renal sympathetic nerve activity was abolished in rats with bilateral nephrectomy but it was not affected by intravenous or intracerebroventricular losartan blockade. Intracerebroventricular angiotensin II produced an increase in mean arterial pressure and efferent renal sympathetic nerve activity whereas intravenous angiotensin II produced a pressor response in absence of increased efferent renal sympathetic nerve activity. Losartan effectively blocked responses to intravenous or intracerebroventricular angiotensin II. Intracerebroventricular administration of furosemide produced no changes in mean arterial pressure, heart rate or efferent renal sympathetic nerve activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Petersen
J S
JS
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242, USA.
DiBona
G F
GF
D000804:Angiotensin II / Q000502:physiology; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D004232:Diuretics / Q000008:administration & dosage / Q000494:pharmacology*; D019856:Ethanolamine; D004983:Ethanolamines / Q000494:pharmacology; D005665:Furosemide / Q000008:administration & dosage / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D019808:Losartan; D008297:Male; D009476:Neurons, Efferent / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000652:urine; D013564:Sympathetic Nervous System / Q000187:drug effects; D013777:Tetrazoles / Q000494:pharmacology
D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D004232:Diuretics; D004983:Ethanolamines; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; D019856:Ethanolamine; D005665:Furosemide; D012083:Renin; D019808:Losartan