Limit Of Cerebral Blood Flow Autoregulation Research Articles

No effect of the angiotensin receptor blocker candesartan on cerebrovascular autoregulation in rats during very high and low sodium intake.

Autoregulation of cerebral blood flow (CBF) denotes that CBF is constant despite fluctuation of blood pressure within wide limits. Inhibition of the renin–angiotensin system (RAS) is known to decrease the lower and upper limits of CBF autoregulation. We have previously shown that this includes inhibition by the angiotensin receptor blocker (ARB) candesartan. In the present study we investigated the influence of the ARB candesartan on the lower limit of CBF autoregulation in two groups of Sprague-Dawley rats, on high (4.0% Na+) and low (0.004% Na+) sodium diet, respectively. Control animals were given the same diet, but no ARB. CBF was studied with the laser Doppler method. Blood pressure was lowered by controlled bleeding. Results revealed that both high and low sodium diet with low and high renin levels respectively block the influence of candesartan on CBF autoregulation. This was expected in rats on a high salt diet with a low renin level, but unexpected in rats with a low salt intake with a high renin level.

Effects of Porta-Systemic Shunting and Ammonia Infusion on Cerebral Blood Flow Autoregulation in the Rat

Portacaval shunting of blood, hyperammonemia, and impaired cerebral blood flow (CBF) autoregulation are assumed to be involved in the development of high intracranial pressure (ICP) in liver failure. In this study, we determined whether CBF autoregulation is impaired by portacaval anastomosis and hyperammonemia. Four groups of pentobarbital-sedated and mechanically ventilated rats were investigated after construction of a portacaval anastomosis or following sham operation. Half of the rats received either infusion of ammonia (55 micromol/kg/minute) or saline for 180 minutes. Arterial pressure and ICP was monitored, and lower limit of CBF autoregulation was determined. Lower limit of autoregulation was preserved in all four groups of studied animals; vehicle lower limits were 40 +/- 2.3, 40 +/- 2, 54 +/- 1, and 51 +/- 3 mmHg in sham-operated rats, sham rats receiving ammonia infusion, portacaval anastomosis-vehicle animals, and portacaval anastomosis-hyperammonemia animals, respectively. The lower limit of auto regulation was higher in portacaval anastomosis rats (p = 0.01) compared to the sham- operated rats. Hyperammonemia in portacaval anastomosis rats did not aggravate this. Portacaval anastomosis and hyperammonemia does not impair the lower limit of CBF autoregulation. However, shunting of portal blood to the systemic circulation shifts the lower limit of autoregulation to higher blood pressure values, making the brain more sensitive to episodes of arterial hypotension.

No effect of angiotensin II AT(2)-receptor antagonist PD 123319 on cerebral blood flow autoregulation.

Blockade of the renin-angiotensin system with angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin AT1-receptor antagonists shift the limits of autoregulation of cerebral blood flow (CBF) towards lower blood pressure (BP). The role of AT2-receptors in the regulation of the cerebral circulation is uncertain. Hence, the present study investigated the effect on CBF autoregulation of blocking of angiotensin AT2-receptors with PD 123319 in spontaneously hypertensive rats (SHR). Anaesthetised and ventilated SHR were given PD 123319, 0.36 mg/kg/min, intravenously, and compared with a control group. CBF was measured by the intracarotid 133xenon injection method and BP was raised by noradrenaline infusion and lowered by controlled haemorrhage in separate groups of rats. The limits of autoregulation were determined by computed least-sum-of-squares analysis. PD 123319 did not influence baseline CBF, but resulted in a minor BP decrease (10 control and 10 treated rats). The lower limit of CBF autoregulation (eight treated and eight control) as well as the upper limit of CBF autoregulation (eight treated and eight control) were not significantly different in PD 123319 and control animals (lower limit treated 102+/-4 mmHg and control 94+/-4; NS, and upper limit treated 171 +/- 10 mmHg and control 162+/-7; NS). These findings indicate that acute AT2-receptor blockade does not influence CBF autoregularion.

Role of ATP-sensitive potassium channels in brain stem circulation during hypotension.

The basilar artery and its branch arterioles dilate actively in response to a marked decrease in blood pressure and maintain cerebral blood flow (CBF) to the brain stem. We tested the hypothesis that ATP-sensitive potassium (KATP) channels play a role in the autoregulatory responses of the brain stem circulation in vivo. In anesthetized Sprague-Dawley rats, local CBF to the brain stem was determined with laser-Doppler flowmetry, and diameters of the basilar artery and branch arterioles were measured through a cranial window during stepwise hemorrhagic hypotension. During topical application of 10(-6) and 10(-5) mol/l of glibenclamide, a selective KATP-channel blocker, the lower limit of CBF autoregulation shifted upward to 60-75 from 30-45 mmHg in the vehicle group. Glibenclamide significantly impaired the dilator response of small arterioles (baseline diameter 45 +/- 2 microns) throughout hypotension (P < 0.03) but did not impair the dilatation of the basilar artery (247 +/- 3 microns) or large arterioles (99 +/- 4 microns). Thus KATP channels appear to play an important role in the regulation of CBF to the the brain stem during hypotension by mediating the compensatory dilatation of small arterioles. In contrast, these channels may not be a major regulator of the vascular tone of larger arteries during hypotension.

Effect of chronic ANG I-converting enzyme inhibition on aging processes. IV. Cerebral blood flow regulation

Age-related changes in systemic arterial blood pressure, basal cerebral blood flow (CBF), and CBF regulatory capacity were investigated in awake 6-, 12-, 24-, and 30-mo-old male Wistar (WAG/Rij) rats, one-half of which received the angiotensin I-converting enzyme inhibitor (ACEI) perindopril from 6 mo onward. There was no age-dependent change in mean arterial blood pressure, basal CBF, or cerebrovascular reactivity to hypercapnia, but the lower limit of CBF autoregulation rose from 70 mmHg at 6 and 12 mo to 90 mmHg in 24- and 30-mo-old animals. ACEI lowered mean arterial blood pressure but had no effect on basal CBF or on cerebrovascular reactivity to hypercapnia. ACEI shifted the lower limit of CBF autoregulation to a 20-mmHg-lower level in 12- and 24-mo animals but not in rats treated for 2 yr, i.e., from the ages of 6 to 30 mo. In conclusion, the main age-related change in CBF regulation was an increase in the lower limit of CBF autoregulation to a higher blood pressure level. Treatment with ACEI partially restored the lower limit of CBF autoregulation.

Effects of the Angiotensin I Converting Enzyme Inhibitor Perindopril on Cerebral Blood Flow in Awake Hypertensive Rats

As chronic hypertension shifts the lower limit of cerebral blood flow (CBF) autoregulation to higher pressure levels, we studied the effects of the angiotensin converting enzyme (ACE) inhibitor, perindopril on mean arterial pressure (mean BP), basal CBF, and CBF autoregulation in awake renovascular hypertensive (2 kidneys, 1 clip model) and spontaneously hypertensive rats (SHR). Blood pressure was measured via a chronically implanted arterial cannula and CBF by hydrogen clearance. Chronic renovascular hypertension, like spontaneous hypertension, caused a marked shift in the lower limit of CBF autoregulation but did not alter basal CBF. In SHR, acute administration of perindopril did not diminish CBF in spite of the fact that BP fell to a level below the lower limit of CBF autoregulation (determined by hypotensive hemorrhage). Chronic treatment of renovascular hypertensive rats with perindopril normalized BP and restored CBF autoregulation.

Cerebral blood flow autoregulation during acute ethanol intoxication in the rat.

Autoregulation of cerebral blood flow (CBF) was studied in anaesthetized rats during acute ethanol intoxication (blood alcohol concentration 2.5 to 3 g/l). For each rat an autoregulation curve was determined: 8-10 CBF measurements were made over the mean arterial pressure range 129 mmHg to 20 mmHg. MAP was raised above the resting level by angiotension II infusion, then lowered by controlled haemorrhage. In control rats, CBF autoregulation was demonstrated within the MAP range 129 mmHg to 70 mmHg: at lower pressure autoregulation was inadequate and CBF fell. In ethanol intoxicated rats CBF autoregulation was demonstrated within the MAP range 129 mmHg to 50 mmHg: at lower pressure CBF fell. Although the lower limit of CBF autoregulation was thus at an MAP 20 mmHg less than in control rats, this probably reflects suppression of cerebral metabolism, rather than an effect of ethanol on CBF autoregulation per se.