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Centre National de la Recherche Scientifique Unité Mixte de Recherche 5014, Institut Fédératif de Recherche Cardio-vasculaire 39, Faculté de Pharmacie, Université Claude Bernard Lyon 1, Lyon 69373, France
These experiments examined
whether the conscious sinoaortic baroreceptor-denervated (SAD) rat,
owing to its high spontaneous arterial pressure (AP) variability, might
represent a model for renal blood flow (RBF) autoregulation studies. In
eight SAD and six baroreceptor-intact rats, AP and RBF were recorded
(1-h periods) before and after furosemide (10 mg/kg followed by 10 mg · kg
1 · h
1 iv)
administration. In control conditions, AP variability was markedly enhanced in SAD rats (coefficient of variation: 16.0 ± 1.2 vs. 5.4 ± 0.5% in intact rats), whereas RBF variability was
only slightly increased (8.7 ± 0.6 vs. 6.1 ± 0.5% in
intact rats), suggesting buffering by autoregulatory mechanisms. In SAD rats, but not in intact rats, the AP-RBF relationships could be modeled
with a four-parameter sigmoid Weibull equation
(r2 = 0.24 ± 0.07, 3,600 data
pairs/rat), allowing for estimation of an autoregulatory plateau
(10.1 ± 0.7 ml/min) and a lower limit of RBF autoregulation
(PLL = 93 ± 6 mmHg, defined as AP at RBF 5%
below the plateau). After furosemide treatment, autoregulation curves
(r2 = 0.49 ± 0.07) in SAD rats were
shifted downward (plateau = 8.6 ± 0.8 ml/min) and rightward
(PLL = 102 ± 5 mmHg). In five of six intact
rats, PLL became measurable (104 ± 1 mmHg), albeit
with limited accuracy (r2 = 0.09 ± 0.03). In conclusion, the conscious SAD rat offers the possibility of
describing RBF autoregulation curves under dynamic, unforced
conditions. The tubuloglomerular feedback and myogenic mechanisms
cooperate in setting PLL and thus in stabilizing RBF during
spontaneous depressor episodes.
arterial pressure variability; furosemide; modeling
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