Selective Blockade of AT1 Receptor Attenuates Impairment of Hypotensive Autoregulation and Improves Cerebral Blood Flow after Brain Injury in the Newborn Pig

2003 ◽  
Vol 99 (5) ◽  
pp. 1118-1124 ◽  
Author(s):  
Dimitry Baranov ◽  
William M. Armstead
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Angiotensin Ii ◽  
Receptor Activation ◽  
At1 Receptor ◽  
Sham Control ◽  
Fluid Percussion ◽  
Fluid Percussion Injury ◽  
At1 Antagonist ◽  
Severe Hypotension

Background Fluid percussion injury (FPI) in piglets produces vasoconstriction of pial arteries (PAs), decreases in cerebral blood flow (CBF), and impairment of hypotensive autoregulation. Two types of angiotensin II receptors, AT1 and AT2, have been identified in the brain. This study characterized the effect of pretreatment with AT1- and AT2-selective antagonists on CBF and hypotensive autoregulation after FPI. Methods Fluid percussion injury was induced in chloralose-anesthetized newborn pigs equipped with closed cranial windows. CBF was determined by the radiolabeled microsphere technique. Results Moderate and severe hypotension (71 +/- 3, 53 +/- 2, and 40 +/- 1 mmHg for normotension, moderate hypotension, and severe hypotension, respectively) elicited PA dilation without changes in CBF in sham control piglets. The AT1 antagonist ZD 7155 partially restored impaired hypotension-induced PA dilation after FPI (19 +/- 1 and 34 +/- 1 vs. 5 +/- 1 and 7 +/- 1 vs. 12 +/- 1 and 20 +/- 3% for PA dilation during moderate and severe hypotension in sham control, FPI, and FPI + ZD 7155 animals, respectively). ZD 7155 also blunted the reductions in CBF during normotension and hypotension observed in untreated animals (43 +/- 4, 38 +/- 5, and 55 +/- 3 vs. 32 +/- 4, 19 +/- 2, and 27 +/- 5% CBF reductions during normotension, moderate hypotension, and severe hypotension in untreated and pretreated animals, respectively). The AT2 selective antagonist PD 123,319 did not restore hypotension-induced PA dilation and did not prevent decreases in CBF observed during normotension and moderate and severe hypotension after FPI. Conclusion These data indicate that blockade of the AT1 and not the AT2 receptor diminished the reduction in hypotensive PA dilation after FPI. AT1 blockade also blunted the decrease in CBF during normotension as well as the further decrease in CBF observed during hypotension after FPI. These data suggest that AT1 receptor activation by angiotensin II contributes to cerebrovascular dysregulation during hypotension after FPI.

Autoregulation of cerebral blood flow after experimental fluid percussion injury of the brain

1980 ◽  
Vol 53 (4) ◽  
pp. 500-511 ◽  
Author(s):  
W. Lewelt ◽  
L. W. Jenkins ◽  
J. Douglas Miller
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Brain Injury ◽  
Intracranial Pressure ◽  
Severe Injury ◽  
Content Type ◽  
Fluid Percussion ◽  
Arterial Blood ◽  
Fluid Percussion Injury ◽  
The Brain

✓ To test the hypothesis that concussive brain injury impairs autoregulation of cerebral blood flow (CBF), 24 cats were subjected to hemorrhagic hypotension in 10-mm Hg increments while measurements were made of arterial and intracranial pressure, CBF, and arterial blood gases. Eight cats served as controls, while eight were subjected to mild fluid percussion injury of the brain (1.5 to 2.2 atmospheres) and eight to severe injury (2.8 to 4.8 atmospheres). Injury produced only transient changes in arterial and intracranial pressure, and no change in resting CBF. Impairment of autoregulation was found in injured animals, more pronounced in the severe-injury group. This could not be explained on the basis of intracranial hypertension, hypoxemia, hypercarbia, or brain damage localized to the area of the blood flow electrodes. It is, therefore, concluded that concussive brain injury produces a generalized loss of autoregulation for at least several hours following injury.

scholarly journals The angiotensin II type I receptor contributes to impaired cerebral blood flow autoregulation caused by placental ischemia in pregnant rats

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Junie P. Warrington ◽  
Fan Fan ◽  
Jeremy Duncan ◽  
Mark W. Cunningham ◽  
Babette B. LaMarca ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Angiotensin Ii ◽  
Renin Angiotensin System ◽  
At1 Receptor ◽  
Type I ◽  
Pregnant Rats ◽  
Doppler Flowmetry ◽  
Cerebrovascular Function ◽  
Placental Ischemia

Abstract Background Placental ischemia and hypertension, characteristic features of preeclampsia, are associated with impaired cerebral blood flow (CBF) autoregulation and cerebral edema. However, the factors that contribute to these cerebral abnormalities are not clear. Several lines of evidence suggest that angiotensin II can impact cerebrovascular function; however, the role of the renin angiotensin system in cerebrovascular function during placental ischemia has not been examined. We tested whether the angiotensin type 1 (AT1) receptor contributes to impaired CBF autoregulation in pregnant rats with placental ischemia caused by surgically reducing uterine perfusion pressure. Methods Placental ischemic or sham operated rats were treated with vehicle or losartan from gestational day (GD) 14 to 19 in the drinking water. On GD 19, we assessed CBF autoregulation in anesthetized rats using laser Doppler flowmetry. Results Placental ischemic rats had impaired CBF autoregulation that was attenuated by treatment with losartan. In addition, we examined whether an agonistic autoantibody to the AT1 receptor (AT1-AA), reported to be present in preeclamptic women, contributes to impaired CBF autoregulation. Purified rat AT1-AA or vehicle was infused into pregnant rats from GD 12 to 19 via mini-osmotic pumps after which CBF autoregulation was assessed. AT1-AA infusion impaired CBF autoregulation but did not affect brain water content. Conclusions These results suggest that the impaired CBF autoregulation associated with placental ischemia is due, at least in part, to activation of the AT1 receptor and that the RAS may interact with other placental factors to promote cerebrovascular changes common to preeclampsia.

scholarly journals Angiotensin II Disrupts Neurovascular Coupling by Potentiating Calcium Increases in Astrocytic Endfeet

2021 ◽  
Author(s):  
Michaël Boily ◽  
Lin Li ◽  
Diane Vallerand ◽  
Hélène Girouard
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Angiotensin Ii ◽  
Dicarboxylic Acid ◽  
Neurovascular Coupling ◽  
At1 Receptor ◽  
Ang Ii ◽  
Vascular Response ◽  
Intracellular Ca ◽  
Astrocytic Endfeet

Background Angiotensin II (Ang II), a critical mediator of hypertension, impairs neurovascular coupling. Since astrocytes are key regulators of neurovascular coupling, we sought to investigate whether Ang II impairs neurovascular coupling through modulation of astrocytic Ca 2+ signaling. Methods and Results Using laser Doppler flowmetry, we found that Ang II attenuates cerebral blood flow elevations induced by whisker stimulation or the metabotropic glutamate receptors agonist, 1S, 3R‐1‐aminocyclopentane‐ trans ‐1,3‐dicarboxylic acid ( P <0.01). In acute brain slices, Ang II shifted the vascular response induced by 1S, 3R‐1‐aminocyclopentane‐ trans ‐1,3‐dicarboxylic acid towards vasoconstriction ( P <0.05). The resting and 1S, 3R‐1‐aminocyclopentane‐ trans ‐1,3‐dicarboxylic acid–induced Ca 2+ levels in the astrocytic endfeet were more elevated in the presence of Ang II ( P <0.01). Both effects were reversed by the AT1 receptor antagonist, candesartan ( P <0.01 for diameter and P <0.05 for calcium levels). Using photolysis of caged Ca 2+ in astrocytic endfeet or pre‐incubation of 1,2‐Bis(2‐aminophenoxy)ethane‐ N,N,N',N' ‐tetra‐acetic acid tetrakis (acetoxymethyl ester), we demonstrated the link between potentiated Ca 2+ elevation and impaired vascular response in the presence of Ang II ( P <0.001 and P <0.05, respectively). Both intracellular Ca 2+ mobilization and Ca 2+ influx through transient receptor potential vanilloid 4 mediated Ang II‐induced astrocytic Ca 2+ elevation, since blockade of these pathways significantly prevented the intracellular Ca 2+ in response to 1S, 3R‐1‐aminocyclopentane‐ trans ‐1,3‐dicarboxylic acid ( P <0.05). Conclusions These results suggest that Ang II through its AT1 receptor potentiates the astrocytic Ca 2+ responses to a level that promotes vasoconstriction over vasodilation, thus altering cerebral blood flow increases in response to neuronal activity.

scholarly journals Normal values of cerebral blood flow velocities in neonates

2010 ◽  
Vol 138 (3-4) ◽  
pp. 186-191 ◽  
Author(s):  
Brankica Vasiljevic ◽  
Miroslava Gojnic ◽  
Svjetlana Maglajlic-Djukic ◽  
Olga Antonovic
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Normal Values ◽  
Color Doppler ◽  
Ductus Arteriosus ◽  
Resistance Index ◽  
Severe Hypotension ◽  
The Mean ◽  
Blood Flow Velocities ◽  
Flow Velocities

Introduction. There was used color Doppler ultrasonography (cD-USI), allowing simultaneous examination of parenchymal and vascular cerebral structures. The evaluation of blood flow velocities in cerebral arteries is important in the assessment of cerebral circulation in hypoxic-ischaemic and haemorrhagic brain damage in neonates. Objective. The aim of this study was to estimate normal values of cerebral blood flow velocities (CBFV) and Doppler indices - pulsatility index (PI) and resistance index (RI) - in the anterior cerebral artery (ACA) during the first days of life in infants. Methods. CBFV, PI and RI were obtained during the first week of life with cD-US in 70 infants divided in four groups of gestational age (GA): ?28 gestational weeks (GW); 29-32 GW; 33-36 GW; and ?37 GW. Infants with congenital malformations, severe perinatal asphyxia, cerebral haemorrhagic lesion, DAP or severe hypotension were excluded. Results. The mean GA of infants was 34.5?5.5 GW (range 26-40 GW) and the mean birth weight (BW) was 2540?950 g (range 750-4000 g). In the 1st group of 10 infants, ?28 GW, the mean BW was 950?110 g and values of RI were 0.59?0.10 and PI 1.06?0.080. In the 2nd group of 20 infants, 29-32 GW, the mean BW was 1350?290 g and values of RI were 0.60?0.10 and PI 1.10?0.15. In the 3rd group of 20 infants, 33-36 GW, the mean BW was 1950?750 g and values of RI were 0.63?0.08 and PI 1.15?0.30. In the 4th group of 20 infants, ?37 GW, the mean BW was 3540?950 g and values of RI were 0.65?0.05 and PI 1.18?0.35. Conclusion. Values of CBFV progressively increase with GA and BW due to progressive increase of cardiac output, blood pressure and closing of ductus arteriosus. Values of RI and PI gradually increase with GA and BW as a result of progressive maturation and opening of vascular cerebral bed with a reduction of the cerebrovascular resistance.

scholarly journals The Angiotensin II Type 1—Receptor Blocker Candesartan Increases Cerebral Blood Flow, Reduces Infarct Size, and Improves Neurologic Outcome after Transient Cerebral Ischemia in Rats

2004 ◽  
Vol 24 (4) ◽  
pp. 467-474 ◽  
Author(s):  
Tobias Engelhorn ◽  
Sophia Goerike ◽  
Arnd Doerfler ◽  
Christine Okorn ◽  
Michael Forsting ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Angiotensin Ii ◽  
Cerebral Ischemia ◽  
Infarct Size ◽  
Laser Doppler Flowmetry ◽  
Transient Cerebral Ischemia ◽  
Doppler Flowmetry ◽  
Treatment Regimens

The goal of the present study was to test the impact of administration time of the angiotensin II type 1–receptor blocker candesartan on cerebral blood flow (CBF), infarct size, and neuroscore in transient cerebral ischemia. Therefore, 1-hour middle cerebral artery occlusion (MCAO) was followed by reperfusion. Rats received 0.5-mg/kg candesartan intravenously 2 hours before MCAO (pretreatment), 24 hours after MCAO, every 24 hours after MCAO, or 2 hours before and every 24 hours after MCAO. Infarct size (mm3) and a neuroscore at day 7 were compared with controls. CBF was quantified by radiolabeled microspheres and laser-Doppler flowmetry. Compared with controls (95 ± 8), infarct size in candesartan-treated groups was smaller (59 ± 5, 68 ± 10, 28 ± 3, and 15 ± 3, respectively; P < 0.05). Although there was no difference in neuroscore between pretreatment and controls (1.55 ± 0.18, 1.80 ± 0.13), other treatment regimens resulted in improved neuroscores (1.33 ± 0.16, 1.11 ± 0.11, 0.73 ± 0.15; P < 0.05). CBF in pretreated animals at 0.5 hours after MCAO was significantly higher than in controls (0.58 ± 0.09 mL · g−1 ·· min−1 and 44% ± 7% of baseline compared with 0.49 ± 0.06 mL · g−1 ·· min−1 and 37% ± 6%, microspheres and laser-Doppler flowmetry; P < 0.05). Thus, candesartan reduces infarct size even if administered only during reperfusion. Apart from pretreatment, other treatment regimens result in significantly improved neuroscores. In the acute phase of cerebral ischemia, candesartan increases CBF.

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