title: ANG II receptor blockade and arterial baroreflex regulation of renal nerve activity in cardiac failure.
abstract: In cardiac failure, efferent renal sympathetic nerve activity (ERSNA) and the activity of the renin-angiotensin system are increased, and arterial baroreflex regulation of ERSNA is attenuated. We examined the effect of intravenous and intracerebroventricular angiotensin II AT receptor blockade with losartan on the arterial baroreflex regulation of ERSNA in conscious control (C) and congestive heart failure (CHF) rats. Intravenous losartan (10 mg/kg, 21.7 mumol/kg) decreased arterial pressure more in CHF than in C rats (-28 +/- 3 vs. -20 +/- 3 mmHg, P < 0.05). After restoration of arterial pressure to the prelosartan value with methoxamine infusion, ERSNA was decreased more in CHF than in C rats (-23 +/- 4 vs. -1 +/- 2%, P < 0.05). Maximal gain of arterial baroreflex control of ERSNA (Gmax) was lower in CHF compared with C rats (-1.94 +/- 0.10 vs. -3.78 +/- 0.21%/mmHg, P < 0.05). Intravenous losartan increased Gmax in CHF (to -3.01 +/- 0.14%/mmHg, P < 0.05) but not in C rats (to -3.56 +/- 0.19%/mmHg). Intracerebroventricular losartan (4.61 micrograms, 10 nmol) did not affect arterial pressure but decreased ERSNA more in CHF than in C rats (-13 +/- 2 vs. -8 +/- 3%, P < 0.05). Like intravenous losartan, intracerebroventricular losartan increased Gmax in CHF (from -2.11 +/- 0.18 to -3.21 +/- 0.30%/mmHg, P < 0.05) but not in C rats (from -3.98 +/- 0.25 to -3.84 +/- 0.22%/mmHg). These results suggest that increased activity of the renin-angiotensin system contributes to the increase in ERSNA and its abnormal arterial baroreflex regulation in cardiac failure.
authors.affiliation: Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, USA.
authors.forename: G F
authors.initials: GF
authors.lastname: DiBona
authors.forename: S Y
authors.initials: SY
authors.lastname: Jones
authors.forename: V L
authors.initials: VL
authors.lastname: Brooks
mesh_terms: D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001158:Arteries / Q000294:innervation*; D017704:Baroreflex / Q000502:physiology*; D001713:Biphenyl Compounds / Q000494:pharmacology; D006333:Heart Failure / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D007668:Kidney / Q000294:innervation*; D019808:Losartan; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology*; D013777:Tetrazoles / Q000494:pharmacology
chemical_list: D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D009599:Nitroprusside; D008729:Methoxamine; D019808:Losartan