Role of sympathetic tone in BSO-induced hypertension in mice.
BACKGROUND
We investigated the contribution of the sympathetic tone to the hypertension induced by chronic administration of buthionine sulfoximine (BSO) and characterized this model in mice.


METHODS
Three experiments were performed. In experiment I, four groups of CBA-C57 male mice were used: controls and three groups that received oral BSO at 5, 10, or 20 mmol/l. In experiment II, the alpha(1)-adrenergic blocker prazosin was orally administered (10 mg/100 ml) to control and BSO-treated mice. All treatments were maintained for 5 weeks. Body weight (BW), tail blood pressure (BP), and heart rate (HR) were measured weekly. Direct mean arterial pressure (MAP) and morphological, metabolic, plasma, and renal variables were measured at the end of the experiments. In experiment III, the acute response of MAP and HR to the ganglionic blocker pentolinium (10 mg/kg intravenous) was used to further evaluate the sympathetic contribution to BP and HR in control and BSO-treated mice.


RESULTS
BSO produced dose-related increases in BP (control, 115 +/- 0.5; BSO-5, 141 +/- 0.5; BSO-10, 151 +/- 0.9; BSO-20, 163 +/- 1.1 mm Hg) and HR and augmented plasma noradrenaline, brainstem isoprostane levels, and total urinary isoprostane excretion. BSO did not produce cardiac hypertrophy and did not modify metabolic or plasma variables, or creatinine clearance, proteinuria, or renal morphology. Chronic prazosin markedly reduced MAP (control, 101 +/- 4.7; prazosin, 95 +/- 1.29; BSO-10, 130 +/- 2.9; BSO-10 +/- prazosin, 98 +/- 0.9) and HR. Acute pentolinium produced a greater percentage MAP (control, 43 +/- 4.2; BSO-10, 66 +/- 4.5) and HR decrease in BSO-treated mice vs. controls.


CONCLUSIONS
Sympathetic tone plays a major role in the increased BP and HR of BSO hypertensive mice.
Rodríguez-Gómez
Isabel
I
Departamento de Fisiología, Granada, Spain.
Baca
Yolanda
Y
Moreno
Juan M
JM
Wangensteen
Rosemary
R
Perez-Abud
Rocío
R
Payá
Jorge A
JA
O'Valle
Francisco
F
Vargas
Félix
F
D058668:Adrenergic alpha-1 Receptor Antagonists; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D019328:Buthionine Sulfoximine; D005730:Ganglionic Blockers / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D028421:Isoprostanes / Q000378:metabolism; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D018384:Oxidative Stress / Q000502:physiology; D010425:Pentolinium Tartrate / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000502:physiology*
D058668:Adrenergic alpha-1 Receptor Antagonists; D005730:Ganglionic Blockers; D028421:Isoprostanes; D019328:Buthionine Sulfoximine; D010425:Pentolinium Tartrate; D011224:Prazosin