Sodium intake, angiotensin II receptor blockade, and baroreflex function in conscious rats.
The hypothesis that endogenous angiotensin II (Ang II) chronically supports baroreflex control of lumbar sympathetic nerve activity (LSNA) and heart rate (HR) via AT1 but not AT2 receptors was tested in conscious, normotensive rats. Rats were fed either a sodium deficient diet (LS) to increase circulating Ang II or a high-sodium diet (HS) for 2 to 3 weeks. One to two days after surgery to implant catheters and nerve electrodes, baroreflex curves were produced before and 40 minutes after intravenous administration of the AT1 antagonist losartan (10 mg/kg) or the AT2 antagonist PD123319 (500 micrograms/kg + 50 micrograms.kg-1.min-1). Mean arterial pressure (MAP) after losartan was maintained at basal levels with methoxamine. Forty minutes after losartan in LS rats, LSNA (46 +/- 5 to 22 +/- 1% max) and HR (414 +/- 7 to 387 +/- 8 bpm) were decreased (P < .05). Losartan decreased reflex control of LSNA more in LS than in HS rats (P < .05), as indicated by reductions in maximum LSNA (98 +/- 2 to 78 +/- 3% max) and minimum LSNA (42 +/- 5 to 21 +/- 5% max). Losartan also shifted reflex control of LSNA to a lower pressure in both groups, but the effect was larger in LS rats (-21 +/- 3 [LS] versus -9 +/- 2 [HS] mm Hg at basal LSNA; P < .05). Maximum gain was unaltered in either group. Similarly, losartan reduced maximum HR (534 +/- 6 to 495 +/- 9 bpm) and shifted the HR curve leftward (114 +/- 5 to 105 +/- 4 mm Hg) in LS but not in HS rats. In general, no changes were observed in MAP or baroreflex control of LSNA and HR after PD123319 in LS rats. These results suggest that in conscious, normotensive LS rats, endogenous Ang II supports LSNA and HR over a wide MAP range via AT1 but not AT2 receptors.
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Department of Physiology and Pharmacology, Oregon Health Sciences University, Portland 97201-3098, USA.
Brooks
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D057911:Angiotensin Receptor Antagonists; D000818:Animals; D017704:Baroreflex / Q000187:drug effects* / Q000502:physiology; D001713:Biphenyl Compounds / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan; D008161:Lumbosacral Region; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000502:physiology; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage*; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology; D013777:Tetrazoles / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D017673:Sodium Chloride, Dietary; D013777:Tetrazoles; D019808:Losartan