ANG II chronically supports renal and lumbar sympathetic activity in sodium-deprived, conscious rats.
The hypothesis that chronic elevations in endogenous angiotensin II (ANG II) increase sympathetic outflow in conscious, normotensive rats was tested by determining if acute blockade of ANG II receptors with losartan (10 mg/kg iv) decreases renal sympathetic nerve activity (RSNA), lumbar sympathetic nerve activity (LSNA), or heart rate (HR) more in rats with higher ANG II levels due to a low sodium (LS) diet compared with a control sodium (CS) or high sodium (HS) diet. In LS rats, losartan decreased (P < 0.05) mean arterial pressure (MAP) in two phases: an immediate decrease of 23 +/- 2 mmHg and a slower fall to 35 +/- 4 mmHg below control 40 min postlosartan. Five minutes after losartan, RSNA (149 +/- 13%), LSNA (143 +/- 5%), and HR (109 +/- 2%) were increased (P < 0.05). Despite further falls in MAP, the elevation in RSNA and HR remained constant, and LSNA decreased toward control (119 +/- 4%). After restoration of MAP to basal levels with methoxamine or phenylephrine infusion, RSNA (46 +/- 8%), LSNA (49 +/- 11%), and HR (76 +/- 2%) were suppressed (P < 0.05). In CS rats, losartan also initially decreased (P < 0.05) MAP by 6 +/- 2 mmHg and increased (P < 0.05) RSNA to 129 +/- 13%. When MAP was returned to control, RSNA was decreased (70 +/- 8%; P < 0.05) but less than in LS rats. In contrast, no changes in MAP, RSNA, LSNA, or HR were observed after losartan in HS rats. In conclusion, endogenous ANG II chronically supports RSNA, LSNA, and HR in conscious, normotensive low and normal sodium intake rats.
Xu
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Department of Physiology and Pharmacology, Oregon Health Sciences University, Portland 97201-3098, USA.
Brooks
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VL
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002496:Central Venous Pressure / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D007668:Kidney / Q000294:innervation*; D019808:Losartan; D008161:Lumbosacral Region; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000172:deficiency*; D013564:Sympathetic Nervous System / Q000502:physiology*; D013777:Tetrazoles / Q000494:pharmacology; D013997:Time Factors
D000316:Adrenergic alpha-Agonists; D000889:Anti-Arrhythmia Agents; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; D010656:Phenylephrine; D012964:Sodium; D008729:Methoxamine; D019808:Losartan