Coupling of cerebral blood flow to neuronal activation: role of adenosine and nitric oxide

1994 ◽  
Vol 267 (1) ◽  
pp. H296-H301 ◽  
Author(s):  
U. Dirnagl ◽  
K. Niwa ◽  
U. Lindauer ◽  
A. Villringer
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Receptor Antagonist ◽  
Barrel Cortex ◽  
No Synthase ◽  
Neuronal Activation ◽  
Whisker Stimulation ◽  
Relationship Of

We studied the role and relationship of the putative mediators of coupling of cerebral blood flow (CBF) and neuronal activation, adenosine (Ado) and nitric oxide (NO). Topical brain application over the whisker barrel cortex of anesthetized rats (n = 24) of the Ado receptor antagonist theophylline (Theo, 5 x 10(-5) M) for 30 min reduced the CBF response to deflection of the contralateral whiskers from 17.9 +/- 3.0% of baseline to 10.6 +/- 2.7% (P < 0.05). Coapplication of Theo (5 x 10(-5) M) and the NO synthase blocker N omega-nitro-L-arginine (L-NNA, 10(-3) M) for 30 min led to a further reduction in the CBF response to whisker stimulation to 7.5 +/- 1.3% (P < 0.05 compared with Theo alone). The CBF effect of sodium nitroprusside (10(-5) M) was not affected by Theo-L-NNA coapplication (122 +/- 25 vs. 140 +/- 25%, n = 5). Application of adenosine deaminase (1 U/ml, n = 5) reduced the CBF response to whisker stimulation from 18.2 +/- 0.7 to 10.7 +/- 1.9% (P < 0.05). Superfusion of L-NNA (10(-3) M, 30 min, n = 7) attenuated the CBF response to application of Ado (10(-4) M) from 39.4 +/- 10.4 to 22.9 +/- 10.5% (P < 0.05). N omega-nitro-D-arginine did not affect the CBF response to Ado (n = 5). We conclude that 1) Ado is involved in coupling of CBF to neuronal activation, 2) NO is involved in this response as well, and 3) there is an interaction between the vasodilator pathways of Ado and NO.

Role of nitric oxide in the coupling of cerebral blood flow to neuronal activation in rats

1993 ◽  
Vol 149 (1) ◽  
pp. 43-46 ◽  
Author(s):  
Ulrich Dirnagl ◽  
Ute Lindauer ◽  
Arno Villringer
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Neuronal Activation

Role of nitric oxide in angiotensin IV-induced increases in cerebral blood flow

1998 ◽  
Vol 74 (2-3) ◽  
pp. 185-192 ◽  
Author(s):  
Enikö A. Kramár ◽  
Radhika Krishnan ◽  
Joseph W. Harding ◽  
John W. Wright
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Angiotensin Iv

Hemoglobin, NO, and 20-HETE interactions in mediating cerebral vasoconstriction following SAH

2006 ◽  
Vol 290 (1) ◽  
pp. R84-R89 ◽  
Author(s):  
Kazuhiko Takeuchi ◽  
Noriyuki Miyata ◽  
Marija Renic ◽  
David R. Harder ◽  
Richard J. Roman
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Subarachnoid Hemorrhage ◽  
Methyl Ester ◽  
Cerebral Vasoconstriction ◽  
Vasoactive Factors ◽  
Vasoconstrictor Response

Recent studies have indicated that 20-hydroxyeicosatetraenoic acid (20-HETE) contributes to the fall in cerebral blood flow (CBF) after subarachnoid hemorrhage (SAH), but the factors that stimulate the production of 20-HETE are unknown. This study examines the role of vasoactive factors released by clotting blood vs. the scavenging of nitric oxide (NO) by hemoglobin (Hb) in the fall in CBF after SAH. Intracisternal (icv) injection of blood produced a greater and more prolonged (120 vs. 30 min) decrease in CBF than that produced by a 4% solution of Hb. Pretreating rats with Nω-nitro-l-arginine methyl ester (l-NAME; 10 mg/kg iv) to block the synthesis of NO had no effect on the fall in CBF produced by an icv injection of blood. l-NAME enhanced rather than attenuated the fall in CBF produced by an icv injection of Hb. Blockade of the synthesis of 20-HETE with TS-011 (0.1 mg/kg iv) prevented the sustained fall in CBF produced by an icv injection of blood and the transient vasoconstrictor response to Hb. Hb (0.1%) reduced the diameter of the basilar artery (BA) of rats in vitro by 10 ± 2%. This response was reversed by TS-011 (100 nM). Pretreatment of vessels with l-NAME (300 μM) reduced the diameter of BA and blocked the subsequent vasoconstrictor response to the addition of Hb to the bath. TS-011 returned the diameter of vessels exposed to l-NAME and Hb to that of control. These results suggest that the fall in CBF after SAH is largely due to the release of vasoactive factors by clotting blood rather than the scavenging of NO by Hb and that 20-HETE contributes the vasoconstrictor response of cerebral vessels to both Hb and blood.

scholarly journals The role of the endothelium in the hyperemic response to passive leg movement: looking beyond nitric oxide

2020 ◽  
Author(s):  
Joel D. Trinity ◽  
Oh Sung Kwon ◽  
Ryan M. Broxterman ◽  
Jayson R. Gifford ◽  
Andrew C. Kithas ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Vascular Function ◽  
No Synthase ◽  
Ketorolac Tromethamine ◽  
Arterial Infusion ◽  
Healthy Men ◽  
Leg Movement ◽  
Hyperemic Response

Passive leg movement (PLM) evokes a robust and predominantly nitric oxide (NO)-mediated increase in blood flow that declines with age and disease. Consequently, PLM is becoming increasingly accepted as a sensitive assessment of endothelium-mediated vascular function. However, a substantial PLM-induced hyperemic response is still evoked despite NO synthase (NOS) inhibition. Therefore, in 9 young healthy men (25±4 yrs), this investigation aimed to determine if the combination of two potent endothelium-dependent vasodilators, specifically prostaglandin (PG) and endothelium-derived hyperpolarizing factor (EDHF), account for the remaining hyperemic response to the two variants of PLM, PLM (60 movements) and single PLM (sPLM, 1 movement) when NOS is inhibited. The leg blood flow (LBF, Doppler ultrasound) response to PLM and sPLM following the intra-arterial infusion of NG-monomethyl L-arginine (L-NMMA), to inhibit NOS, was compared to the combined inhibition of NOS, cyclooxygenase (COX), and cytochrome P450 (CYP450) by L-NMMA, ketorolac tromethamine (KET), and fluconazole (FLUC), respectively. NOS inhibition attenuated the overall LBF (LBFAUC) response to both PLM (control: 456±194, L-NMMA: 168±127 ml, p<0.01) and sPLM (control: 185±171, L-NMMA: 62±31 ml, p=0.03). The combined inhibition of NOS, COX, and CYP450 (i.e. L-NMMA+KET+FLUC) did not further attenuate the hyperemic responses to PLM (LBFAUC: 271±97 ml, p>0.05) or sPLM (LBFAUC: 72±45 ml, p>0.05). Therefore, PG and EDHF do not collectively contribute to the non-NOS-derived NO-mediated, endothelium-dependent, hyperemic response to either PLM or sPLM in healthy young men. These findings add to the mounting evidence and understanding of the vasodilatory pathways assessed by the PLM and sPLM vascular function tests.

Nitric oxide, prostaglandins, and impaired cerebral blood flow autoregulation in group B streptococcal neonatal meningitis

2000 ◽  
Vol 78 (3) ◽  
pp. 217-227 ◽  
Author(s):  
Carmen Mertineit ◽  
Jacqueline Samlalsingh-Parker ◽  
Maria Glibetic ◽  
Ginette Ricard ◽  
Francisco JD Noya ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nitric Oxide ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Early Onset ◽  
No Synthase ◽  
Neonatal Meningitis ◽  
Cerebrovascular Autoregulation ◽  
Upper Limit ◽  
Group B

Impaired autoregulation of cerebral blood flow (CBF) contributes to CNS damage during neonatal meningitis. We tested (i) the hypothesis that cerebrovascular autoregulation is impaired during early onset group B streptococcal (GBS) meningitis, (ii) whether this impairment is regulated by vasoactive mediators such as prostaglandins and (or) nitric oxide (NO), and (iii) whether this impairment is preventable by specific and (or) nonspecific inhibitors: dexamethasone, ibuprofen, and Nω-nitro-L-arginine, a NO inhibitor. Sterile saline or 109colony-forming units (cfu) of heat-killed GBS was injected into the cerebral ventricle of newborn piglets. CBF autoregulation was determined by altering cerebral perfusion pressure (CPP) with balloon-tipped catheters placed in the aorta. GBS produced a narrow range of CBF autoregulation due to an impairment at the upper limit of CPP. We report that in vivo in the early stages (first 2 h) of induced GBS inflammation (i) GBS impairs the upper limit of cerebrovascular autoregulation; (ii) ibuprofen, dexamethasone, and Nω-nitro-L-arginine not only prevent this GBS-induced autoregulatory impairment but improve the range of cerebrovascular autoregulation; (iii) these autoregulatory changes do not involve circulating cerebral prostanoids; and (iv) the observed changes correlate with the induction of NO synthase gene expression. Thus, acute early onset GBS-induced impairment of the upper limit of CBF autoregulation can be correlated with increases of NO synthase production, suggesting that NO is a vasoactive mediator of CBF.Key words: cerebrovascular autoregulation, group B Streptococcus, neonatal meningitis, anti-inflammatory agents, prostanoids, nitric oxide synthase, gene expression, nitric oxide.

Nitric oxide mediation of chemoregulation but not autoregulation of cerebral blood flow in primates

1996 ◽  
Vol 84 (1) ◽  
pp. 71-78 ◽  
Author(s):  
B. Gregory Thompson ◽  
Ryszard M. Pluta ◽  
Mary E. Girton ◽  
Edward H. Oldfield
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
No Production ◽  
Direct Role ◽  
Content Type ◽  
Continuous Release ◽  
Fine Print

✓ The authors sought to develop a model for assessing in vivo regulation of cerebral vasoregulation by nitric oxide (NO), originally described as endothelial-derived relaxing factor, and to use this model to establish the role of NO in the regulation of cerebral blood flow (CBF) in primates. By using regional intraarterial perfusion, the function of NO in cerebral vasoregulation was examined without producing confounding systemic physiological effects. Issues examined were: whether resting vasomotor tone requires NO; whether NO mediates vasodilation during chemoregulation and autoregulation of CBF; and whether there is a relationship between the degree of hypercapnia and hypotension and NO production. Twelve anesthetized (0.5% isoflurane) cynomolgus monkeys were monitored continuously for cortical CBF, PaCO2, and mean arterial pressure (MAP), which were systematically altered to provide control and experimental curves of chemoregulation (CBF vs. PaCO2) and autoregulation (CBF vs. MAP) during continuous intracarotid infusion of 1) saline and 2) an NO synthase inhibitor (NOSI), either l-n-monomethyl arginine or nitro l-arginine. During basal conditions (PaCO2 of 38–42 mm Hg) NOSI infusion of internal carotid artery (ICA) reduced cortical CBF from 62 (saline) to 53 ml/100 g/per minute (p < 0.01), although there was no effect on MAP. Increased CBF in response to hypercapnia was completely blocked by ICA NOSI. The difference in regional (r)CBF between ICA saline and NOSI infusion increased linearly with PaCO2 when PaCO2 was greater than 40 mm Hg, indicating a graded relationship of NO production, increasing PaCO2, and increasing CBF. Diminution of CBF with NOSI infusion was reversed by simultaneous ICA infusion of l-arginine, indicating a direct role of NO synthesis in the chemoregulation of CBF. Hypotension and hypertension were induced with trimethaphan camsylate (Arfonad) and phenylephrine at constant PaCO2 (40 ± 1 mm Hg). Autoregulation in response to changes in MAP from 50 to 140 mm Hg was unaffected by ICA infusion of NOSI. In primates, cerebral vascular tone is modulated in vivo by NO; continuous release of NO is necessary to maintain homeostatic cerebral vasodilation; vasodilation during chemoregulation of CBF is mediated directly by NO production; autoregulatory vasodilation with hypotension is not mediated by NO; and increasing PaCO2 induces increased NO production.

scholarly journals Vasodilator tone in the llama fetus: the role of nitric oxide during normoxemia and hypoxemia

2005 ◽  
Vol 289 (3) ◽  
pp. R776-R783 ◽  
Author(s):  
Emilia M. Sanhueza ◽  
Raquel A. Riquelme ◽  
Emilio A. Herrera ◽  
Dino A. Giussani ◽  
Carlos E. Blanco ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Vascular Resistance ◽  
Control Group ◽  
Blood Flows ◽  
Vasoconstrictor Effect ◽  
Vascular Beds ◽  
Oxide Synthase

The fetal llama responds to hypoxemia, with a marked peripheral vasoconstriction but, unlike the sheep, with little or no increase in cerebral blood flow. We tested the hypothesis that the role of nitric oxide (NO) may be increased during hypoxemia in this species, to counterbalance a strong vasoconstrictor effect. Ten fetal llamas were operated under general anesthesia. Mean arterial pressure (MAP), heart rate, cardiac output, total vascular resistance, blood flows, and vascular resistances in cerebral, carotid and femoral vascular beds were determined. Two groups were studied, one with nitric oxide synthase (NOS) blocker NG-nitro-l-arginine methyl ester (l-NAME), and the other with 0.9% NaCl (control group), during normoxemia, hypoxemia, and recovery. During normoxemia, l-NAME produced an increase in fetal MAP and a rapid bradycardia. Cerebral, carotid, and femoral vascular resistance increased and blood flow decreased to carotid and femoral beds, while cerebral blood flow did not change significantly. However, during hypoxemia cerebral and carotid vascular resistance fell by 44% from its value in normoxemia after l-NAME, although femoral vascular resistance progressively increased and remained high during recovery. We conclude that in the llama fetus: 1) NO has an important role in maintaining a vasodilator tone during both normoxemia and hypoxemia in cerebral and femoral vascular beds and 2) during hypoxemia, NOS blockade unmasked the action of other vasodilator agents that contribute, with nitric oxide, to preserving blood flow and oxygen delivery to the tissues.

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