Effect of nephrectomy and captopril on autoregulation of cerebral blood flow in rats

Abstract

. Effect of nephrectomy and captopril on autoregulation of cerebral blood flow in rats. Am J Physiol Heart Circ Physiol 285: H1097-H1104, 2003. First published May 15, 2003 10.1152/ajpheart.00098. 2003.-The present study investigated the effect of circulating versus locally present renin on cerebral blood flow (CBF) and its autoregulation in rats. CBF was measured repetitively with the intracarotid 133 Xe injection method, whereas blood pressure was lowered to determine the lower limit of autoregulation. To remove renin from the blood, rats were bilaterally nephrectomized and kept alive with peritoneal dialysis for 48 h. Five groups of animals were studied: 1) nephrectomized dialyzed rats, 2) nephrectomized dialyzed rats given a single intravenous dose of the angiotensinconverting enzyme inhibitor captopril (10 mg/kg), 3) sham nephrectomized and dialyzed rats, 4) rats receiving drugs as dialyzed rats but no surgery, and 5) rats given the same diet as the other groups but no drugs and no surgery. Baseline blood pressure was significantly lower in nephrectomized rats compared with controls. Nephrectomy, captopril, sham operation, or dialysis did not influence baseline CBF. The lower limit of CBF autoregulation was significantly lower in nephrectomized (53 Ϯ 4 mmHg) and sham-operated (58 Ϯ 4 mmHg) rats compared with diet control rats (78 Ϯ 3 mmHg). Captopril significantly decreased the lower limit in nephrectomized rats (35 Ϯ 2 mmHg). Thus removal of circulating renin caused no change in the lower limit of autoregulation. By contrast, captopril lowered the lower limit even in the absence of circulating renin and hence appeared to exert its effect on components of the renin-angiotensin system in the cerebral resistance vessel walls. renin-angiotensin system; nephrectomy; captopril CEREBRAL BLOOD FLOW (CBF) is autoregulated, i.e., kept constant over a wide range of blood pressure. Autoregulation is mainly a feature of the smaller cerebral resistance vessels (4,(6)(7)(8)17). Blockade of the reninangiotensin system by angiotensin-converting enzyme (ACE) inhibitors, e.g., captopril (2, 3, 30), shifts both the lower and upper limits of CBF autoregulation toward lower blood pressure, possibly by releasing angiotensin II-mediated tone in the larger cerebral resistance vessels (21), with a contribution of bradykinin accumulation (27). Angiotensin II subtype 1 (AT1) receptor antagonists and agonists also shift the limits of CBF autoregulation (15,26,33). Modulation of the angiotensin II AT2 receptors appears to have limited influence on CBF autoregulation (5, 15, 26).The renin-angiotensin system may influence CBF autoregulation from the circulating blood or by in situ vessel wall activity of components of the system (14). The aim of the present study was to investigate the influence of circulating versus local renin on CBF and its autoregulation. The study was carried out in nephrectomized dialyzed rats in which no circulating renin was present. The animals were studied with or without captopril blockade and compared with ...

Carotid compression: Investigation of cerebral autoregulative reserve in rats

“…(54 ± 10 mmHg), our data are in close agreement to data published from other groups (Hossmann, 1994;Panerai, 1998;Pedersen et al, 2003;Tonnesen et al, 2005). Stating the results of Tonnesen et al (2005), we also found a sloped rather than a perfect horizontal autoregulative plateau.…”

“…From the unstimulated cerebral blood flow recordings, the lower limit of autoregulation was calculated according to published procedures (Pedersen et al, 2003). In short, the lower limit was identified as the mean arterial blood pressure that corresponds to the intersection between two linear regression lines: one horizontal line above the lower limit (the plateau), and another line below the lower limit.…”

The frequency response of cerebral autoregulation

“…A post hoc analysis of the laser-Doppler data plotted as a function of cerebral perfusion pressure was used to delineate a discrete LLA for each subject using piecewise linear regression (17). The cohort LLA was 39 mmHg (28 -45 mmHg), which is consistent with precedent work in neonatal swine (12,16).…”

Cerebral Pressure Autoregulation and Vasoreactivity in the Newborn Rat

“…Pressure autoregulation and its lower limit were calculated as described by Pedersen et al (24). In brief, the lower autoregulatory limit was obtained from the intersection of two lines found by the least square technique, and a constraint was put on the horizontal line.…”