Cerebral blood flow regulation in neonatal rabbits is altered by chronic cocaine administration

Maternal cocaine abuse has several deleterious effects in the newborn, including perinatal asphyxia, hypoxia, and hypercapnia. We hypothesized that chronic cocaine exposure during development may alter cerebral blood flow (CBF) regulation. We studied 16 neonatal rabbits that had received cocaine (20 mg/kg, i.p. b.i.d.) or saline since birth. Changes in CBF were measured by laser doppler flowmetry before (baseline), and during hypercapnia (FiCO₂=7.5%), hypoxia (FiO₂=12%), and asphyxia (apnea for 1 min). During hypercapnia, CBF increased less in cocaine than in control animals (28±3% vs. 69±10%, P<0.05). During hypoxia, CBF increased similarly in both groups. During reventilation after asphyxia, CBF increased more in cocaine than in control animals (391±52% vs. 225±43%, P<0.05). Chronic cocaine exposure during brain development appears to alter CBF regulation to hypercapnia and asphyxia, which may put the drug exposed newborn at risk for neurologic injury around birth.     

Impaired cerebral autoregulation 24 h after induction of transient unilateral focal ischaemia in the rat

Cerebral blood flow (CBF) and cerebral autoregulation have been investigated 24 h after transient focal ischaemia in the rat. Cerebral blood flow was measured autoradiographically before and during a moderate hypotensive challenge, to test autoregulatory responses, using two CBF tracers, (99m)Tc-d,l-hexamethylproyleneamine oxide and 14C-iodoantipyrine. Prior to induced hypotension, CBF was significantly reduced within areas of infarction; cortex (28 +/- 20 compared with 109 +/- 23 mL/100 g/min contralateral to ischaemic focus, P = 0.001) and caudate (57 +/- 31 compared with 141 +/- 32 mL/100 g/min contralaterally, P = 0.005). The hypotensive challenge (mean arterial pressure reduced to 60 mmHg by increasing halothane concentration) did not compromise grey matter autoregulation in the contralateral hemisphere; CBF data were not significantly different at normotension and during hypotension. However, in the ipsilateral hemisphere, a significant volume of cortex adjacent to the infarct, which exhibited normal flow at normotension, became oligaemic during the hypotensive challenge (e.g. frontal parietal cortex 109 +/- 15% to 65 +/- 15% of cerebellar flow, P < 0.01). This resulted in a 2.5-fold increase in the volume of cortex which fell below 50% cerebellar flow (39 +/- 34 to 97 +/- 46 mm3, P = 0.003). Moderate hypotension induced a significant reduction in CBF in both ipsilateral and contralateral subcortical white matter (P < 0.01). In peri-infarct caudate tissue, CBF was not significantly affected by hypotension. In conclusion, a significant volume of histologically normal cortex within the middle cerebral artery territory was found to have essentially normal levels of CBF but impaired autoregulatory function at 24 h post-ischaemia.     

The role of adenosine in CBF increases during hypoxia in young vs aged rats

The role of adenosine in the regional cerebral blood flow (rCBF) response to hypoxia was evaluated in young (6 month) and aged (26-28 month) F344 rats using theophylline, an adenosine antagonist. Regional CBF was measured with radioactive microspheres under control anesthetized conditions (70% N2O, 30% O2) and at two levels of hypoxia (CaO2 = 8.7-9.0 ml . 100ml-1 and 3.2-3.7 ml . 100ml-1). Without theophylline infusion, CBF increases were similar between young and aged rats during moderate hypoxia but were increased more in young during severe hypoxia. Intracerebrovascular theophylline infusion significantly attenuated the increase in CBF during both moderate and severe hypoxia and decreased the difference between young and aged rats. Theophylline infusion produced no significant effect on the increase in CBF produced by hypercapnia, indicating the specificity of the treatment for hypoxic induced CBF changes and adenosine release. Intracerebrovascular infusion of adenosine had no effect on CBF, presumably due to the presence of the blood brain barrier. The results suggest that adenosine plays a major role in CBF increases during both moderate and severe hypoxia and in the difference in response to hypoxia between young and aged rats.     

Determination of rat cerebral cortical blood volume changes by capillary mean transit time analysis during hypoxia, hypercapnia and hyperventilation

Changes in cerebral blood volume due to augmented or diminished numbers of blood-perfused capillaries can be studied in small animals by optical methods. Capillary mean transit time was determined by detection of the passage of a hemodilution bolus through a region of the parietal cerebral cortical surface, using a reflectance spectrophotometer through a small craniotomy in chloral hydrate-anesthetized rats. Local cerebral blood flow was determined in the same region by the butanol indicator-fractionation method. Blood volume was calculated from the product of blood flow and transit time. Normoxic, normocapnic values for these variables were blood flow = 144 ml/100 g/min; mean transit time = 1.41 s; and blood volume = 3.4 ml/100 g. Mean transit time reached a minimum (1.1 s) with moderate hypoxia or hypercapnia. Combined hypoxia and hypercapnia did not result in any further decrease in mean transit time although blood flow was much higher than either hypoxia or hypercapnia alone. The maximum blood volume recorded during hypercapnic hypoxia (12.1 ml/100 g) was 3.6 times greater than that at normoxic normocapnia, which suggests that under control conditions in the anesthetized rat considerably less than 100% of the cerebral capillaries were actively perfusing the tissue. These studies demonstrate that optical methods can be used to quantitatively measure blood volume. The data suggest that capillary recruitment is a physiologically significant phenomenon in rat cerebral cortex.     

Hemispheric blood flow in the rat after unilateral common carotid occlusion: evolution with time

Acute occlusion of one common carotid artery in the anesthetized normocapnic rat results in a moderate cerebral blood flow (CBF) decrease in both cerebral hemispheres. No asymmetrical perfusion is observed when the overall flow in each hemisphere is considered. The increase in blood flow which normally occurs in hypercapnia is strongly impaired in the cerebral hemisphere on the occluded side resulting in an important asymmetrical hemispheric perfusion. The days (1, 5, 15, 30) following unilateral carotid occlusion normal control CBF values are found in both hemispheres in normocapnic conditions. Hemispheric perfusion asymmetry in hypercapnia also becomes progressively less pronounced with time but a slight asymmetry still persists one month after unilateral carotid occlusion.     

Cerebral blood flow and metabolic rate early and late in prolonged epileptic seizures induced in rats by bicuculline.

Cerebral blood flow (CBF) and cerebral metablic rate for oxygen (CMRO2) have been studied during sustained epileptic seizures induced by bicuculline (1-2 mg/kg, i.v.) in paralysed Wistar rats, artificially ventilated with nitrous oxide/oxygen. CBF was determined by venous outflow collection, and by 133Xe desaturation, using sagittal sinus blood (for cerebral cortical flow) or retroglenoid venous blood (for 'whole brain' flow). The procedure employed ensured that arterial oxygenation remained normal and blood glucose concentration was normal or high throughout the seizure. Arterial hypotension was prevented by the infusion of donor blood. CBF increased concurrently with seizure onset, reaching a maximum nine times higher than control value after 15-60 s. This was due to a marked rise in mean arterial pressure (to greater than 180 torr) and a dramatic fall in cerebrovascular resistance to less than 15 per cent of control). Subsequently, with decreasing blood pressure, CBF slowly diminished, being more than four times higher than control at 20 min, and slightly less than three times higher than control at two hours. The different procedures for measuring CBF gave closely similar results. A threefold increase relative to control CMRO2 (7-6 ml/100 g-1/min-1 for 'whole brain,' and 10-2 ml/100 g-1/min-1 for cerebral cortex) was measured after 1-20 min of seizure activity (utilizing either the venous outflow or the 133Xe desaturation procedure for CBF determination). After two hours of seizure activity CMR02 was still more than twice as high as the control. This high metabolic rate during sustained seizure activity will increase the susceptibility of the brain to 'ischaemic' damage during prolonged seizures in man in which an additional metabolic stress may be imposed by cerebral hypoxia, arterial hypotension, hyperpyrexia or hypoglycaemia.     

Cerebral blood flow response to propranolol in streptozotocin diabetic rats

The influence of propranolol on cerebral blood flow (CBF) was tested in streptozotocin diabetic rats and in control animals. Resting CBF values were 40% lower in the diabetic rats compared with controls. Intravenous injection of propranolol (2 mg kg-1) decreased CBF significantly in the control group; the CBF decreased for 15 min after propranolol injection and returned to baseline values after 90 min. In the diabetic rats, the CBF declined steadily but this decrease did not reach significance, even after 90 min. Impaired beta-adrenergic mechanisms may be an important factor in the CBF alterations which occur in diabetes mellitus. Further, it is suggested that an impaired CBF response may play a role in CNS lesions in diabetic patients treated with beta antagonists.     

Cerebrovascular response to hypoxia in young vs aged rats

Cerebrovascular responses of young and aged rats were tested to graded levels of hypoxia using a modification of the Levine ischemic-hypoxic rat model in which one carotid artery was ligated. Rats were anesthetized with 70% N2O, 30% O2 and cortical and subcortical cerebral blood flow (CBF) were measured with radioactive microspheres. CBF and cerebral cortical oxygen consumption (CMRO2) were measured under control conditions and during hypoxia with arterial oxygen content maintained at approximately 9, 5 and 3 ml . dl-1. CBF responses in cortical and subcortical tissues were similar between young and aged under control conditions and during moderate hypoxia (CaO2 = 9 ml . dl-1). Maximum cerebrovascular responses to severe hypoxia were greater in young than in aged rats and these trends were significant in both ligated and unligated cortical tissue (p less than 0.05). CMRO2 was maintained at control levels during moderate hypoxia but decreased significantly more in aged than in young rats when CaO2 was decreased to 3 ml . dl-1. These results suggest that baseline CBF and the sensitivity of cerebrovascular receptors to moderate hypoxia are similar in young vs aged rats but that maximum reactivity severe hypoxia is attenuated in aged subjects. CBF measured after one minute of hypoxia, before the induction of brain tissue acidosis, produced no significant change in the CBF response to hypoxia or in the difference between young and aged rats. Brain tissue pH changes do not appear to be the major factor for mediating CBF increases during hypoxia in young or aged rats, although it may interact with other mediators of the response.     

Influence of the heme-oxygenase pathway on cerebrocortical blood flow

Heme-oxygenase (HO)-derived carbon monoxide (CO) is generated in the cardiovascular and in the central nervous systems. Endogenous CO exerts direct vascular effects and has also been shown to inhibit nitric oxide synthase (NOS). In the current study, the heme-oxygenase blockade [zinc deuteroporphyrin 2,4-bis glycol (ZnDPBG), 45 micromol/kg intraperitoneally] decreased cerebral CO production and increased cerebrocortical blood flow (CBF) in anesthetized rats. This latter effect was abrogated by the NOS blockade (50 mg/kg L-NAME intravenously). Furthermore, inhibition of CO production had no effect on stepwise hypoxia/hypercapnia-stimulated increases in CBF. Our results indicate that endogenous CO reduces the resting CBF via inhibition of NOS but fails to influence the CBF response to hypoxia and hypercapnia in adult rats.     

Role of substantia innominata in cerebral blood flow autoregulation

Ascending projections from the substantia innominata (SI) may have an important role in the regulation of cerebral blood flow (CBF). However, several reports have suggested that unilateral lesion of the SI does not affect CBF autoregulation. On the other hand, it is also reported that several cortical and subcortical functions may be regulated not only by ipsilateral SI, but also by contralateral SI. Thus, the objective of this study is to test the hypothesis that bilateral lesions of the SI affect CBF autoregulation. Experiments were performed on anesthetized male Sprague-Dawley rats. Ibotenic acid or physiological saline was microinjected into bilateral SI. Rats were classified into four groups as follows: bilateral SI lesion rats (ibotenic acid was injected bilaterally), left or right SI lesion rats (ibotenic acid was injected into the unilateral SI and saline into the contralateral SI), and control rats (saline was injected bilaterally). Ten days after injection, CBF in the left frontal cortex was measured by laser-Doppler flowmetry during stepwise controlled hemorrhagic hypotension. In bilateral SI lesion rats, CBF was started to decrease significantly at 80 mm Hg (p<0.01). In the other three groups, CBF was well maintained until 50 mm Hg. Changes in CBF through stepwise hypotension in bilateral SI lesion rats were significantly different from the other groups (p<0.01). These results suggest that bilateral SI regulates cortical vasodilator mechanisms during hemorrhagic hypotension. Under unilateral SI lesion, some compensatory effects from the contralateral SI may maintain CBF autoregulation.     

Changes in human cerebral blood flow and cerebral blood volume during hypercapnia and hypocapnia measured by positron emission tomography.

Hypercapnia induces cerebral vasodilation and increases cerebral blood flow (CBF), and hypocapnia induces cerebral vasoconstriction and decreases CBF. The relation between changes in CBF and cerebral blood volume (CBV) during hypercapnia and hypocapnia in humans, however, is not clear. Both CBF and CBV were measured at rest and during hypercapnia and hypocapnia in nine healthy subjects by positron emission tomography. The vascular responses to hypercapnia in terms of CBF and CBV were 6.0 +/- 2.6%/mm Hg and 1.8 +/- 1.3%/mm Hg, respectively, and those to hypocapnia were -3.5 +/- 0.6%/mm Hg and -1.3 +/- 1.0%/mm Hg, respectively. The relation between CBF and CBV was CBV = 1.09 CBF0.29. The increase in CBF was greater than that in CBV during hypercapnia, indicating an increase in vascular blood velocity. The degree of decrease in CBF during hypocapnia was greater than that in CBV, indicating a decrease in vascular blood velocity. The relation between changes in CBF and CBV during hypercapnia was similar to that during neural activation; however, the relation during hypocapnia was different from that during neural deactivation observed in crossed cerebellar diaschisis. This suggests that augmentation of CBF and CBV might be governed by a similar microcirculatory mechanism between neural activation and hypercapnia, but diminution of CBF and CBV might be governed by a different mechanism between neural deactivation and hypocapnia.     

Effect of carotid ligation on cerebral blood flow in baboons: 2. Response to hypoxia and haemorrhagic hypertension

Cerebral blood flow (CBF) measurements were carried out in two groups of anaesthetized normocapnic baboons. In the first group of five animals the effect of hypoxia on the CBF before and after ipsilateral carotid artery ligation was studied. The results showed that, although after ipsilateral carotid ligation there was little change in the CBF at normal PaO₂, at hypoxia there was only 20% rise in the CBF as compared with an 80% rise before the carotid ligation. In the second group of 10 animals, effects of haemorrhagic hypotension on the CBF after ipsilateral carotid artery ligation were estimated. The results indicated impairment of autoregulatory response of the cerebral circulation.     

Cerebral blood flow and oxygen consumption in the rat brain after lesions of the noradrenergic locus coeruleus system

The effects of lesions of the locus coeruleus neuron system on cerebral metabolic rate for oxygen (CMR_O2) and blood flow (CBF) was evaluated in paralyzed and mechanically ventilated rats, using a¹³³xenon modification of the Kety-Schmidt inert gas technique. Bilateral electrothermic lesions of the nucleus locus coeruleus or bilateral 6-hydroxydopamine lesions of its ascending bindle caused no significant change in CBF or CMR_O2. The 6-hydroxydopamine lesions did not influence the CBF and CMR_O2 responses to hypercapnia and hypoxia.It is concluded that the locus coeruleus does not exert any resting tone on CBF and CMR_O2 and that no influence on the CBF and CMR_O2 responses to hypercapnia and hypoxia is mediated via its ascending projections.     

Chronic hyperglycemic diabetes in the rat is associated with a selective impairment of cerebral vasodilatory responses

Diabetes has been reported to impair vasodilatory responses in the peripheral vascular tissue. However, little is known about vasodilatory function in the diabetic brain. We therefore studied, in the N2O-sedated, paralyzed, and artificially ventilated rat, the effects of chronic hyperglycemic diabetes on the cerebral blood flow (CBF) responses to 3 acutely imposed vasodilatory stimuli: hypoglycemia (HG) (plasma glucose = 1.6-1.9 mumol ml-1), hypoxia (HX) (PaO2 = 35-38 mm Hg), or hypercarbia HC) (PaCO2 = 75-78 mm Hg). In addition, we evaluated the somatosensory evoked potential (SSEP) and plasma catecholamine changes in rats exposed to acute glycemic reductions. Diabetes was induced via streptozotocin (STZ, 60 mg kg-1 i.p.). All results in diabetic rats were compared to those obtained in age-matched nondiabetic controls. The animals were studied at 6-8 weeks (HG experiments) or 4-6 months (HG, HX, and HC experiments) post-STZ. Values for CBF were obtained for the cortex (CX), subcortex (SC), brainstem (BS), and cerebellum (CE) employing radiolabeled microspheres. Up to three CBF determinations were made in each animal. In 6-8 week diabetics vs. controls, CBF increased to a lesser value in the CX, SC, and BS (p less than 0.05). Thus, in the diabetics, going from chronic hyperglycemia to acute hypoglycemia, CBF values (in ml 100 g-1 min-1 +/- SD) increased (p less than 0.05) from 89 +/- 22 to 221 +/- 57 in the CX, from 82 +/- 21 to 160 +/- 52 in the SC, and from 79 +/- 34 to 237 +/- 125 in the BS. In controls, going from normoglycemia to acute hypoglycemia, the CBF changes (p less than 0.05) were 128 +/- 27 to 350 +/- 219 (CX), 117 +/- 11 to 358 +/- 206 (SC), and 130 +/- 29 to 452 +/- 254 (BS). CBF changes and absolute values in the CE were similar in the two groups. At 4-6 months post-STZ, a complete loss of the hypoglycemic CBF response was found in the CX, SC, and CE. In the BS, a CBF response to hypoglycemia was seen in the diabetic rats, with the CBF increasing from 114 +/- 28 (hyperglycemia) to 270 +/- 204 ml 100 g-1 min-1 (p less than 0.05), compared to a change from 147 +/- 36 (normoglycemia) to 455 +/- 299 ml 100 g-1 min-1 (p less than 0.05) in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prostacyclin, indomethacin and the cerebral circulation

The effect of intracarotid prostacyclin (PGI2) on cerebral blood flow (CBF) was measured by the 133xenon intracarotid injection technique in 8 baboons. Intracarotid prostacyclin increased CBF by 22% at 10(-7) g/kg/min and by 71% at 5 x 10(-6) g/kg/min, accompanied by systemic hypotension and tachycardia. The effects of PGI2 (10(-7) g/kg/min) were not potentiated by transient opening of the blood-brain barrier with the intracarotid hypertonic urea technique. At hypercapnia, the vasoconstrictor effect of indomethacin on the cerebral circulation was reversed by PGI2. These results support our suggestion that a prostaglandin, in particular PGI2, is required for hypercapnia to produce full cerebral vasodilatation. In separate experiments, following craniectomy in 5 cats, PGI2, but not its stable metabolite 6-keto-PGF1 alpha, dilated pial arterioles when locally injected into the mock CSF overlying the arteriole.     

Atropine decreases drinking but not feeding and induces less hypothalamic acetylcholine release in diabetic rats

Drinking, feeding and hypothalamic extracellular acetylcholine (ACh) release was measured before and after the administration of several doses of atropine sulfate in streptozotocin (STZ)-diabetic and normal rats. Drinking but not feeding was dose-relatedly decreased by i.p. or intrahypothalamic injections of atropine in STZ-diabetic rats. Hypothalamic ACh release, as measured by microdialysis, increased less (dose-related) in diabetic than normal rats following an i.p. administration of atropine. Ach basal levels were the same in both groups. These results are discussed in terms of a hyperactive hypothalamic cholinergic (muscarinic) system involved in the diabetic polydipsia.     

Central angiotensin converting enzyme facilitates memory impairment in intracerebroventricular streptozotocin treated rats

Preclinical and clinical studies indicated involvement of renin angiotensin system (RAS) in memory functions. However, exact role of RAS in cognition is still ambiguous. Our aim was to explore how angiotensin converting enzyme (ACE) modulates memory in experimental model of memory impairment. Memory deficit was induced by intracerebroventricular administration of streptozotocin (STZ, 3 mg/kg) in rats. Perindopril, an ACE inhibitor, was given for 21 days and memory function was evaluated by Morris water maze test. Cerebral blood flow (CBF) was measured by laser doppler flowmetry. The biochemical and expression studies were done in cortex and hippocampus of rat brain after the completion of behavioral studies. STZ caused impairment in memory along with significant reduction in CBF, ATP level and elevated oxidative and nitrosative stress. The activity and mRNA expression of acetylcholinesterase (AChE) and ACE were also increased in rat brain regions following STZ administration. However, serum ACE activity remained unaffected. Treatment with perindopril dose dependently improved memory by increasing energy metabolism and CBF. Perindopril also decreased oxidative and nitrosative stress, activity and mRNA expression of AChE and ACE in STZ treated rat. Further, ACE inhibition mitigated STZ induced neurodegeneration as observed in histopathological studies. Moreover, perindopril per se improved memory and CBF, decreased oxidative stress with no effect on AChE activity and expression. However, perindopril per se significantly reduced ACE activity but increased mRNA expression of ACE in rat brain. These results suggest that ACE occupies a pivotal role in STZ induced memory deficit thus implicating central RAS in cognition.     

Cerebral blood flow and BOLD fMRI responses to hypoxia in awake and anesthetized rats

This study investigated the functional MRI responses to graded hypoxia in awake/restrained and anesthetized animals by measuring cerebral blood flow (CBF) and blood oxygenation (BOLD) changes and estimating changes in cerebral metabolic rate of oxygen (CMRO2). Hypoxia in isoflurane anesthetized rats reduced blood pressure but did not change heart rate and respiration rate. In contrast, hypoxia in awake animals showed compensatory responses by sustaining blood pressure, increasing heart rate and respiration rate. Basal CBF was higher under isoflurane anesthesia than awake state because isoflurane is a vasodilator. Graded hypoxia decreased BOLD signals. Surprisingly, hypoxia also decreased CBF likely because hypoxia induced hypocapnia. Hypoxia-induced CBF and BOLD decreases were smaller in awake, relative to anesthetized, rats at low pO2, but similar at high pO2. CBF leveled off with decreasing hypoxia-induced pCO2 in awake rats, but monotonically decreased in anesthetized rats. CMRO2 estimated using a biophysical BOLD model did not change under mild hypoxia but was reduced under severe hypoxia relative to baseline. These results showed that isoflurane attenuated autonomic responses to hypoxia, hypoxia-induced hypocapnia dominated CBF changes, tissues in awake conditions appeared better oxygenated, and severe hypoxia reduced oxygen metabolism. This study underscored the marked differences in BOLD and CBF MRI responses to hypoxia in vivo between awake and anesthetized conditions and has implications for functional MRI studies of hypoxia in anesthetized animal models.     

Effects of endothelium-derived nitric oxide on cerebral circulation during normoxia and hypoxia in the rat.

The aim of this study was to determine the effects of endogenous nitric oxide (NO) on cerebral blood flow (CBF) and cerebrovascular resistance (CVR) under conditions of normoxia and hypoxia. Experiments were performed on anesthetized, mechanically ventilated Wistar rats. CBF was measured using the intracarotid 133Xe injection technique. NO formation was inhibited by NG-monomethyl-L-arginine (L-NMMA). Administration of L-NMMA (100 mg kg-1 i.v.) during normoxia resulted in an increase in mean arterial blood pressure from 113 +/- 4 to 145 +/- 4 mm Hg (p less than 0.001), a decrease in CBF of 21% (from 91 +/- 4 to 75 +/- 5 ml 100 g-1 min-1, p less than 0.001), and an increase in CVR of 53% (from 1.3 +/- 0.1 to 2.0 +/- 0.2 mm Hg ml-1 100 g min, p less than 0.001). These effects were reversed by i.v. administration of 300 mg kg-1 of L-arginine but not D-arginine. Moreover, the administration of L-NMMA abolished the enhancement of CBF and the diminution in CVR observed during intracarotid infusion of acetylcholine (ACh). The increase in CBF and decrease in CVR during hypoxia in the group of rats that received L-NMMA were similar to that in the control group, although CBF and CVR levels attained during hypoxia in both groups were different. The results show that NO is involved in the maintenance of basal CBF and CVR, and is responsible for the ACh-elicited increase in CBF and the decrease in CVR in rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

Regional cerebral blood flow during hypotension in normotensive and stroke-prone spontaneously hypertensive rats: effect of sympathetic denervation

This study was performed to determine whether, in hypertensive and normotensive rats, chronic sympathetic denervation impairs cerebral vasodilator responses during hypotension, and to determine whether there are regional differences in the autoregulatory response of brain vessels during hypotension. The superior cervical ganglion was removed on one side in stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive (WKY) rats. Cerebral blood flow (CBF) was measured with microspheres when the rats were 5-6 months old. Chronic sympathetic denervation had little or no effect on cerebral vasodilator responses during acute hypotension in SHRSP and WKY. We suggest that the increase in incidence of ischemic infarction that we have observed previously after chronic sympathetic denervation in SHRSP probably is not the result of ischemia during episodes of hypotension. We also observed major regional differences in the response of cerebral vessels during acute hypotension in SHRSP: blood flow to brainstem was preserved better than flow to cerebrum and cerebellum. Thus the "lower limit" of the autoregulatory plateau differs in various regions of the brain in SHRSP.