Abstract-It is not known whether renal blood flow (RBF) is still autoregulated when the kidney is exposed to large transient blood pressure (BP) fluctuations such as those occurring spontaneously in conscious sinoaortic baroreceptordenervated (SAD) rats. In this study, BP and RBF were simultaneously recorded in 8 SAD rats (2 weeks before study) and 8 baroreceptor-intact rats during Ϸ3 hours of spontaneous activity. The kidney used for RBF recordings was denervated to prevent the interference of changes in renal sympathetic tone with autoregulatory mechanisms. In intact rats, RBF variability (coefficient of variation 9.1Ϯ0.8%) was larger (PϽ0.02) than BP variability (5.9Ϯ0.2%). This was mainly because of slow changes in RBF that were unrelated to BP and also to a prominent oscillation of RBF of Ϸ0.25-Hz frequency. Autoregulatory patterns were identified at frequencies Ͻ0. Key Words: autoregulation Ⅲ blood pressure Ⅲ rats Ⅲ denervation A lthough hemodynamic factors are likely to play a role in the progression of renal failure, 1,2 the possible deleterious effects of an exaggerated blood pressure (BP) variability on the kidney have not yet been established. It is often proposed that autoregulatory mechanisms prevent acute changes in systemic BP from being transmitted to the glomerular capillary circulation. 3 Most studies on renal blood flow (RBF) autoregulation have been performed in anesthetized rats, with the use of either induced 4 or spontaneous 5 changes in BP. In the conscious rat, RBF autoregulation has been described by measuring RBF responses to steady-state changes in renal perfusion pressure induced by reversible constrictions of the abdominal aorta above or below the renal arteries. 6,7 This technique suffers from 2 major limitations. First, it is difficult to determine the higher limit of autoregulation because it is impossible to raise renal perfusion pressure by Ͼ20% to 25% with the use of an aortic cuff. Second, the technique overlooks the essentially dynamic nature of autoregulation. 8 Spontaneous autoregulatory patterns have been reported in the renal circulation of conscious rats. 9,10 However, in normal rats with intact baroreceptors, BP varies within a relatively narrow range 10 -12 ; therefore, it is not known whether the kidney is able to cope with transient large fluctuations of BP, such as those occurring spontaneously in the sinoaortic baroreceptor-denervated (SAD) rat. [11][12][13][14] In the present study, RBF and BP were simultaneously recorded during long periods of spontaneous activity in conscious SAD rats. Rats were studied 2 weeks after surgery, ie, in the early chronic phase of denervation, when mean levels of BP are nearly normal and BP variability is markedly increased. 11,14 Sympathetic nerves play a major role in promoting behaviorally coupled changes in RBF 15 and are probably also involved in generating BP fluctuations in SAD rats, at least the acute pressor episodes. 16 To avoid the interference of sympathetically mediated vasoconstriction with autoregulatory responses, t...
Pires, Silene L. S., Claude Julien, Bruno Chapuis, Jean Sassard, and Christian Barrè s. Spontaneous renal blood flow autoregulation curves in conscious sinoaortic baroreceptor-denervated rats. Am J Physiol Renal Physiol 282: F51-F58, 2002. First published August 8, 2001 10.1152/ajprenal.00186.2001.-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 ⅐ kg Ϫ1 ⅐ h Ϫ1 iv) administration. In control conditions, AP variability was markedly enhanced in SAD rats (coefficient of variation: 16.0 Ϯ 1.2 vs. 5.4 Ϯ 0.5% in intact rats), whereas RBF variability was only slightly increased (8.7 Ϯ 0.6 vs. 6.1 Ϯ 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 (r 2 ϭ 0.24 Ϯ 0.07, 3,600 data pairs/rat), allowing for estimation of an autoregulatory plateau (10.1 Ϯ 0.7 ml/min) and a lower limit of RBF autoregulation (PLL ϭ 93 Ϯ 6 mmHg, defined as AP at RBF 5% below the plateau). After furosemide treatment, autoregulation curves (r 2 ϭ 0.49 Ϯ 0.07) in SAD rats were shifted downward (plateau ϭ 8.6 Ϯ 0.8 ml/min) and rightward (PLL ϭ 102 Ϯ 5 mmHg). In five of six intact rats, PLL became measurable (104 Ϯ 1 mmHg), albeit with limited accuracy (r 2 ϭ 0.09 Ϯ 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 AUTOREGULATION OF TOTAL RENAL blood flow (RBF) is usually explored by measuring RBF responses to externally induced stepwise reductions of arterial pressure (AP) in both anesthetized (6,8,11,13,17,21,22) and conscious (2,4,16,18,(24)(25)(26) animals. Steady-state levels of RBF are plotted as a function of AP, which allows the drawing of autoregulation curves from which the plateau and lower pressure limit of RBF autoregulation (P LL ) are estimated. It is not known whether such information can be gained under spontaneous unforced conditions, i.e., using RBF responses to naturally occurring AP fluctuations.The conscious sinoaortic baroreceptor-denervated (SAD) rat is a well-recognized model of exaggerated AP variability, which is characterized by the spontaneous occurrence of pressor and depressor episodes of occasionally large amplitude (3,28). Recently, we have investigated in conscious SAD rats the relationships between AP variability and RBF variability (20). Although AP variability was markedly increased, RBF variability was only slightly increased, suggesting a powerful participa...
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