Blockade of Cerebral Blood Flow Response to Insulin-Induced Hypoglycemia by Caffeine and Glibenclamide in Conscious Rats

The possibility that adenosine and ATP-sensitive potassium channels (KATP) might be involved in the mechanisms of the increases in cerebral blood flow (CBF) that occur in insulin-induced hypoglycemia was examined. Cerebral blood flow was measured by the [14C]iodoantipyrine method in conscious rats during insulin-induced, moderate hypoglycemia (2 to 3 mmol/L glucose in arterial plasma) after intravenous injections of 10 to 20 mg/kg of caffeine, an adenosine receptor antagonist, or intracisternal infusion of 1 to 2 μmol/L glibenclamide, a KATP channel inhibitor. Cerebral blood flow was also measured in corresponding normoglycemic and drug-free control groups. Cerebral blood flow was 51% higher in untreated hypoglycemic than in untreated normoglycemic rats ( P < 0.01). Caffeine had a small, statistically insignificant effect on CBF in normoglycemic rats, but reduced the CBF response to hypoglycemia in a dose-dependent manner, i.e., 27% increase with 10 mg/kg and complete elimination with 20 mg/kg. Chemical determinations by HPLC in extracts of freeze-blown brains showed significant increases in the levels of adenosine and its degradation products, inosine and hypoxanthine, during hypoglycemia ( P < 0.05). Intracisternal glibenclamide had little effect on CBF in normoglycemia, but, like caffeine, produced dose-dependent reductions in the magnitude of the increases in CBF during hypoglycemia, i.e., +66% with glibenclamide-free artificial CSF administration, +25% with 1 μmol/L glibenclamide, and almost complete blockade (+5%) with 2 μmol/L glibenclamide. These results suggest that adenosine and KATP channels may play a role in the increases in CBF during hypoglycemia.

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Role of Mas Receptor Antagonist A799 in Renal Blood Flow Response to Ang 1-7 after Bradykinin Administration in Ovariectomized Estradiol-Treated Rats

Advances in Pharmacological Sciences ◽

10.1155/2015/801053 ◽

2015 ◽

Vol 2015 ◽

pp. 1-9 ◽

Cited By ~ 3

Author(s):

Aghdas Dehghani ◽

Shadan Saberi ◽

Mehdi Nematbakhsh

Keyword(s):

Blood Flow ◽

Renal Blood Flow ◽

Wistar Rats ◽

Group Versus ◽

Dependent Manner ◽

Mas Receptor ◽

Flow Response ◽

Renal Vascular ◽

Dose Dependent

Background. The accompanied role of Mas receptor (MasR), bradykinin (BK), and female sex hormone on renal blood flow (RBF) response to angiotensin 1-7 is not well defined. We investigated the role of MasR antagonist (A779) and BK on RBF response to Ang 1-7 infusion in ovariectomized estradiol-treated rats.Methods. Ovariectomized Wistar rats received estradiol (OVE) or vehicle (OV) for two weeks. Catheterized animals were subjected to BK and A799 infusion and mean arterial pressure (MAP), RBF, and renal vascular resistance (RVR) responses to Ang 1-7 (0, 100, and 300 ng kg−1 min−1) were determined.Results. Percentage change of RBF (%RBF) in response to Ang1-7 infusion increased in a dose-dependent manner. In the presence of BK, when MasR was not blocked, %RBF response to Ang 1-7 in OVE group was greater than OV group significantly (P<0.05). Infusion of 300 ng kg−1 min−1Ang 1-7 increased RBF by6.9±1.9% in OVE group versus0.9±1.8% in OV group. However when MasR was blocked, %RBF response to Ang 1-7 in OV group was greater than OVE group insignificantly.Conclusion. Coadministration of BK and A779 compared to BK alone increased RBF response to Ang 1-7 in vehicle treated rats. Such observation was not seen in estradiol treated rats.

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Intravenous Infusion of Adrenomedullin and Increase in Regional Cerebral Blood Flow and Prevention of Ischemic Brain Injury after Middle Cerebral Artery Occlusion in Rats

Journal of Cerebral Blood Flow & Metabolism ◽

10.1097/00004647-199701000-00004 ◽

1997 ◽

Vol 17 (1) ◽

pp. 19-25 ◽

Cited By ~ 87

Author(s):

Aclan Dogan ◽

Yoshio Suzuki ◽

Naoki Koketsu ◽

Koji Osuka ◽

Kiyoshi Saito ◽

...

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Brain Injury ◽

Intravenous Infusion ◽

Regional Cerebral Blood Flow ◽

Ischemic Brain Injury ◽

Dependent Manner ◽

Regional Cerebral Blood ◽

Ischemic Brain ◽

Dose Dependent

The intravenous infusion of rat adrenomedullin, at concentrations ranging from 0.1 to 1.0 μg/kg/min, for 60 min increased the regional cerebral blood flow (rCBF) in a dose-dependent manner in rats. rCBF was measured using a laser Doppler flowmetry device placed on the surface of the parietal cortex. The increase in rCBF induced by 1.0 μg/kg/min of adrenomedullin was up to 145 ± 10.8% of controls at 60 min (n = 5, p < 0.001). These concentrations of adrenomedullin did not affect systemic blood pressure or other physiologic parameters, including pH, PaCO2, PaO2, hemoglobin, and blood glucose. Repeated infusion of 1.0 μg/kg/min of adrenomedullin at 2-h intervals caused tachyphylaxis (n = 5, p < 0.01). Rat adrenomedullin (1.0 μg/kg/min) demonstrated a more potent effect than the same dose of human adrenomedullin. The C-terminal fragment of human adrenomedullin (0.5 and 5.0 μg/kg/min), adrenomedullin22–52, which did not affect rCBF alone, inhibited the effect of rat adrenomedullin (0.5 μg/kg/min) as a receptor antagonist in a dose-dependent manner. In a model of middle cerebral artery (MCA) occlusion in spontaneously hypertensive rats, pre- and postinfusion of 1.0 μg/kg/min of adrenomedullin suppressed the reduction in rCBF following MCA occlusion (control, 29 ± 15.1%; adrenomedullin group, 45 ± 14.4%; not significant) and decreased the volume of ischemic brain injury (control, 288 ± 35 mm3; adrenomedullin group, 232 ± 35 mm3; p < 0.05). These results suggest that adrenomedullin increases rCBF and prevents ischemic brain injury, partly by increasing the collateral circulation.

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Effect of caffeine on theophyliine on cerebral blood flow response to brain activation: In vitro and in vivo studies

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/sj.jcbfm.9591524.0198 ◽

2005 ◽

Vol 25 (1_suppl) ◽

pp. S198-S198

Author(s):

Joseph R Meno ◽

Thien-son K Nguyen ◽

Elise M Jensen ◽

G Alexander West ◽

Leonid Groysman ◽

...

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Brain Activation ◽

In Vivo Studies ◽

Blood Flow Response ◽

Flow Response

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Effects of NO-Donors on Thrombus Formation and Microcirculation in Cerebral Vessels of the Rat

Thrombosis and Haemostasis ◽

10.1055/s-0038-1650532 ◽

1996 ◽

Vol 76 (01) ◽

pp. 111-117 ◽

Cited By ~ 10

Author(s):

Yasuto Sasaki ◽

Junji Seki ◽

John C Giddings ◽

Junichiro Yamamoto

Keyword(s):

Blood Flow ◽

Thrombus Formation ◽

Dependent Manner ◽

Red Cell ◽

Cell Velocity ◽

Red Cell Velocity ◽

The Mean ◽

Wall Shear ◽

Dose Dependent

SummarySodium nitroprusside (SNP) and 3-morpholinosydnonimine (SIN-1), are known to liberate nitric oxide (NO). In this study the effects of SNP and SIN-1 on thrombus formation in rat cerebral arterioles and venules in vivo were assessed using a helium-neon (He-Ne) laser. SNP infused at doses from 10 Μg/kg/h significantly inhibited thrombus formation in a dose dependent manner. This inhibition of thrombus formation was suppressed by methylene blue. SIN-1 at a dose of 100 Μg/kg/h also demonstrated a significant antithrombotic effect. Moreover, treatment with SNP increased vessel diameter in a dose dependent manner and enhanced the mean red cell velocity measured with a fiber-optic laser-Doppler anemometer microscope (FLDAM). Blood flow, calculated from the mean red cell velocity and vessel diameters was increased significantly during infusion. In contrast, mean wall shear rates in the arterioles and venules were not changed by SNP infusion. The results indicated that SNP and SIN-1 possessed potent antithrombotic activities, whilst SNP increased cerebral blood flow without changing wall shear rate. The findings suggest that the NO released by SNP and SIN-1 may be beneficial for the treatment and protection of cerebral infarction

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Potential Effect of Endothelial Signaling on Cerebral Blood Flow Response to Neural Activation

2021 10th International IEEE/EMBS Conference on Neural Engineering (NER) ◽

10.1109/ner49283.2021.9441110 ◽

2021 ◽

Author(s):

Ramin Pashaie

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Potential Effect ◽

Neural Activation ◽

Blood Flow Response ◽

Flow Response

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Dose-Dependent Effects of Radiation Therapy on Cerebral Blood Flow, Metabolism and Neurocognitive Dysfunction

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2005.07.116 ◽

2005 ◽

Vol 63 ◽

pp. S67 ◽

Cited By ~ 4

Author(s):

C.A. Hahn ◽

S. Zhou ◽

D.H. Renee ◽

T. Shafman ◽

T. Wong ◽

...

Keyword(s):

Blood Flow ◽

Radiation Therapy ◽

Cerebral Blood Flow ◽

Neurocognitive Dysfunction ◽

Effects Of Radiation ◽

Dose Dependent

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Examination of Potential Mechanisms in the Enhancement of Cerebral Blood Flow by Hypoglycemia and Pharmacological Doses of Deoxyglucose

Journal of Cerebral Blood Flow & Metabolism ◽

10.1097/00004647-199701000-00008 ◽

1997 ◽

Vol 17 (1) ◽

pp. 54-63 ◽

Cited By ~ 25

Author(s):

Naoaki Horinaka ◽

Nicole Artz ◽

Jane Jehle ◽

Shinichi Takahashi ◽

Charles Kennedy ◽

...

Keyword(s):

Nitric Oxide ◽

Blood Flow ◽

Cerebral Blood Flow ◽

Glucose Metabolism ◽

Plasma Glucose ◽

Plasma Lactate ◽

Insulin Hypoglycemia ◽

Glucose Levels ◽

Arterial Blood ◽

Arterial Plasma

Cerebral blood flow (CBF) rises when the glucose supply to the brain is limited by hypoglycemia or glucose metabolism is inhibited by pharmacological doses of 2-deoxyglucose (DG). The present studies in unanesthetized rats with insulin-induced hypoglycemia show that the increases in CBF, measured with the [14C]iodoantipyrine method, are relatively small until arterial plasma glucose levels fall to 2.5 to 3.0 m M, at which point CBF rises sharply. A direct effect of insulin on CBF was excluded; insulin administered under euglycemic conditions maintained by glucose injections had no effects on CBF. Insulin administration raised plasma lactate levels and decreased plasma K+ and HCO3– concentrations and arterial pH. These could not, however, be related to the increased CBF because insulin under euglycemic conditions had similar effects without affecting CBF; furthermore, the inhibition of brain glucose metabolism with pharmacological doses (200 mg/kg intravenously) of DG increased CBF, just like insulin hypoglycemia, without altering plasma lactate and K+ levels and arterial blood gas tensions and pH. Nitric oxide also does not appear to mediate the increases in CBF. Chronic blockade of nitric oxide synthase activity by twice daily i.p. injections of NG-nitro-L-arginine methyl ester for 4 days or acutely by a single i.v. injection raised arterial blood pressure and lowered CBF in normoglycemic, hypoglycemic, and DG-treated rats but did not significantly reduce the increases in CBF due to insulin-induced hypoglycemia (arterial plasma glucose levels, 2.5-3 m M) or pharmacological doses of deoxyglucose.

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Hypoxia and Hypotension Transform the Blood Flow Response to Cortical Spreading Depression from Hyperemia into Hypoperfusion in the Rat

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2008.35 ◽

2008 ◽

Vol 28 (7) ◽

pp. 1369-1376 ◽

Cited By ~ 56

Author(s):

Inna Sukhotinsky ◽

Ergin Dilekoz ◽

Michael A Moskowitz ◽

Cenk Ayata

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Cortical Spreading Depression ◽

Spreading Depression ◽

Ischemic Penumbra ◽

Doppler Flowmetry ◽

Blood Flow Response ◽

Flow Response ◽

Normal Rat ◽

Cortex Cérébral

Cortical spreading depression (CSD) evokes a large cerebral blood flow (CBF) increase in normal rat brain. In contrast, in focal ischemic penumbra, CSD-like periinfarct depolarizations (PID) are mainly associated with hypoperfusion. Because PIDs electrophysiologically closely resemble CSD, we tested whether conditions present in ischemic penumbra, such as tissue hypoxia or reduced perfusion pressure, transform the CSD-induced CBF response in nonischemic rat cortex. Cerebral blood flow changes were recorded using laser Doppler flowmetry in rats subjected to hypoxia, hypotension, or both. Under normoxic normotensive conditions, CSD caused a characteristic transient CBF increase (74 ± 7%) occasionally preceded by a small hypoperfusion (−4 ± 2%). Both hypoxia ( pO2 45 ± 3 mm Hg) and hypotension (blood pressure 42 ± 2 mm Hg) independently augmented this initial hypoperfusion (−14 ± 2% normoxic hypotension; −16 ± 6% hypoxic normotension; −21 ± 5% hypoxic hypotension) and diminished the magnitude of hyperemia (44 ± 10% normoxic hypotension; 43 ± 9% hypoxic normotension; 27 ± 6% hypoxic hypotension). Hypotension and, to a much lesser extent, hypoxia increased the duration of hypoperfusion and the DC shift, whereas CSD amplitude remained unchanged. These results suggest that hypoxia and/or hypotension unmask a vasoconstrictive response during CSD in the rat such that, under nonphysiologic conditions (i.e., mimicking ischemic penumbra), the hyperemic response to CSD becomes attenuated resembling the blood flow response during PIDs.

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