scholarly journals The Role of Neuronal Nitric Oxide Synthase in Regulation of Cerebral Blood Flow in Normocapnia and Hypercapnia in Rats

1995 ◽  
Vol 15 (5) ◽  
pp. 774-778 ◽  
Author(s):  
Qiong Wang ◽  
Dale A. Pelligrino ◽  
Verna L. Baughman ◽  
Heidi M. Koenig ◽  
Ronald F. Albrecht
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Nitric Oxide Synthase ◽  
Inhibitory Action ◽  
Neuronal Nitric Oxide Synthase ◽  
Muscarinic Agonist ◽  
Doppler Flowmetry ◽  
Nos Inhibitors ◽  
Oxide Synthase

The nitric oxide synthase (NOS) inhibitors, nitro-L-arginine, its methyl ester, and N-monomethyl-L-arginine, have been shown to attenuate resting CBF and hypercapnia-induced cerebrovasodilation. Those agents nonspecifically inhibit the endothelial and neuronal NOS (eNOS and nNOS). In the present study, we used a novel nNOS inhibitor, 7-nitroindazole (7-NI) to examine the role of nNOS in CBF during normocapnia and hypercapnia in fentanyl/N2O-anesthetized rats. CBF was monitored using laser-Doppler flowmetry. Administration of 7-NI (80 mg kg−1 i.p.) reduced cortical brain NOS activity by 57%, the resting CBF by 19–27%, and the CBF response to hypercapnia by 60%. The 60% reduction was similar in magnitude to the CBF reductions observed in previous studies in which nonspecific NOS inhibitors were used. In the present study, 7-NI did not increase the MABP. Furthermore, the CBF response to oxotremorine, a blood–brain barrier permeant muscarinic agonist that induces cerebrovasodilation via endothelium-derived NO, was unaffected by 7-NI. These results confirmed that 7-NI does not influence eNOS; they also indicated that the effects of 7-NI on the resting CBF and on the CBF response to hypercapnia in this study were solely related to its inhibitory action on nNOS. The results further suggest that the NO synthesized by the action of nNOS participates in regulation of basal CBF and is the major, if not the only, category of NO contributing to the hypercapnic CBF response.

A Unique Role of NO in the Control of Blood Flow

Physiology ◽  
1999 ◽  
Vol 14 (2) ◽  
pp. 74-80 ◽  
Author(s):  
Ulrich Pohl ◽  
Cor de Wit
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Nitric Oxide Synthase ◽  
Vascular Conductance ◽  
Unique Role ◽  
Nos Inhibitors ◽  
Oxide Synthase

Nitric oxide synthase (NOS) inhibitors induce significant vasoconstriction, suggesting an indispensable role of NO as a local vasodilator. This is due mainly to its effects on large arterioles that significantly control arterial conductance while scarcely being regulated by metabolites. NO’s role in adapting vascular conductance to flow is pronounced during (re)active hyperemia and autoregulation.

Isoflurane-induced Cerebral Hyperemia Is Partially Mediated by Nitric Oxide and Epoxyeicosatrienoic Acids in Mice In Vivo 

2002 ◽  
Vol 97 (6) ◽  
pp. 1528-1533 ◽  
Author(s):  
Franz Kehl ◽  
Hui Shen ◽  
Carol Moreno ◽  
Neil E. Farber ◽  
Richard J. Roman ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Nitric Oxide Synthase ◽  
Neuronal Nitric Oxide Synthase ◽  
Epoxyeicosatrienoic Acids ◽  
Acute Administration ◽  
Doppler Flowmetry ◽  
Cortical Blood Flow ◽  
Oxide Synthase ◽  
Cerebral Cortical Blood Flow

Background Despite intense investigation, the mechanism of isoflurane-induced cerebral hyperemia is unclear. The current study was designed to determine the contributions of neuronal nitric oxide synthase, prostaglandins, and epoxyeicosatrienoic acids to isoflurane-induced cerebral hyperemia. Methods Regional cerebral cortical blood flow was measured with laser Doppler flowmetry during stepwise increases of isoflurane from 0.0 to 1.2, 1.8, and 2.4 vol% end-tidal concentration in alpha-chloralose-urethane-anesthetized, C57BL/6 mice before and 45 min after administration of the neuronal nitric oxide synthase inhibitor 7-nitroindazole (7-NI, 40 mg/kg, intraperitoneal), the cyclooxygenase inhibitor indomethacin (INDO, 10 mg/kg, intravenous), and the cytochrome P450 epoxygenase inhibitor N-methylsulfonyl-6-(2-proparglyoxyphenyl)hexanoic acid (PPOH, 20 mg/kg, intravenous). Results Isoflurane increased regional cerebral cortical blood flow by 9 +/- 3, 46 +/- 21, and 101 +/- 26% (SD) at 1.2, 1.8, and 2.4 vol%, respectively. The increases in regional cerebral cortical blood flow were significantly (*P < 0.05) smaller after 7-NI (5 +/- 6, 29 +/- 19*, 68 +/- 15%*) or PPOH (4 +/- 8, 27 +/- 17*, 67 +/- 30%*), but not after administration of INDO (4 +/- 4, 33 +/- 18 [NS], 107 +/- 35% [NS]). The effect of combined treatment with 7-NI, PPOH, and INDO was not additive and was equal to that of either 7-NI or PPOH alone (5 +/- 5, 30 +/- 12*, 76 +/- 24%*). Chronic treatment of mice for 5 days with 7-NI (2 x 40 mg/kg, intraperitoneal) produced similar decreases in regional cerebral cortical blood flow as those seen with acute administration. Neither PPOH nor INDO conferred a significant additional block of the hyperemia in these animals. Conclusions Nitric oxide and epoxyeicosatrienoic acids contribute to isoflurane-induced hyperemia. However, only approximately one third of the cerebral hyperemic response to isoflurane is mediated by autacoids. The remaining part of this response appears to be mediated by a direct action of isoflurane on smooth muscle by some yet-unknown mechanism.

scholarly journals Effect of an Inhibitor of Neuronal Nitric Oxide Synthase 7-Nitroindazole on Cerebral Hemodynamic Response and Brain Excitability in Urethane-Anesthetized Rats

2013 ◽  
pp. S57-S66 ◽  
Author(s):  
C. BROŽÍČKOVÁ ◽  
J. OTÁHAL
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Nitric Oxide Synthase ◽  
Neurovascular Coupling ◽  
Neuronal Nitric Oxide Synthase ◽  
Hemodynamic Response ◽  
Doppler Flowmetry ◽  
Arterial Blood ◽  
Oxide Synthase

The role of neuronal nitric oxide synthase (nNOS) in the pathophysiology of epilepsy and seizures remains disputable. One of the reasons why results from the acute in vivo studies display controversies might be the effect on the regulation of cerebral blood flow (CBF) during pharmacologically induced alterations of NO system. We examined neurovascular coupling in the rat sensorimotor cortex in response to transcallosal stimulation under nNOS inhibition by 7-nitroindazole (7-NI). Adult Wistar rats were anesthetized with urethane and epidural silver EEG electrodes were implanted over sensorimotor cortices. Regional CBF was measured by Laser Doppler Flowmetry (LDF). We catheterized a common carotid artery to measure arterial blood pressure (BP). 7-NI did not significantly affect blood pressure and heart rate. Electrophysiological recordings of evoked potentials (EPs) revealed no effect on their amplitude, rhythmic potentiation or depression of EPs. Transcallosal stimulation of the contralateral cortex induced a frequency dependent rise in CBF. Although 7-NI did not significantly affect basal CBF and cortical excitability, hemodynamic responses to the transcallosal stimulation were diminished implicating a role of nNOS in neurovascular coupling. Urethane anesthesia is suitable for future epileptological experiments. Our findings demonstrate that NO contributes to the hemodynamic response during brain activation.

Role of Neuronal Nitric Oxide Synthase in Regulating Retinal Blood Flow During Flicker-Induced Hyperemia in Cats

2015 ◽  
Vol 56 (5) ◽  
pp. 3113 ◽  
Author(s):  
Takafumi Yoshioka ◽  
Taiji Nagaoka ◽  
Youngseok Song ◽  
Harumasa Yokota ◽  
Tomofumi Tani ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Nitric Oxide Synthase ◽  
Neuronal Nitric Oxide Synthase ◽  
Retinal Blood Flow ◽  
Oxide Synthase

scholarly journals Neuronal nitric oxide synthase regulates regional brain perfusion in healthy humans

2021 ◽  
Author(s):  
Kevin O’Gallagher ◽  
Francesca Puledda ◽  
Owen O’Daly ◽  
Matthew Ryan ◽  
Luke Dancy ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Functional Connectivity ◽  
Nitric Oxide Synthase ◽  
Neuronal Nitric Oxide Synthase ◽  
Healthy Human ◽  
Brain Functional Connectivity ◽  
Oxide Synthase

Abstract Aims Neuronal nitric oxide synthase (nNOS) is highly expressed within the cardiovascular and nervous systems. Studies in genetically modified mice suggest roles in brain blood flow regulation while dysfunctional nNOS signaling is implicated in cerebrovascular ischemia and migraine. Previous human studies have investigated the effects of non-selective NOS inhibition but there has been no direct investigation of the role of nNOS in human cerebrovascular regulation. We hypothesised that inhibition of the tonic effects of nNOS would result in global or localized changes in cerebral blood flow, as well as changes in functional brain connectivity. Methods and Results We investigated the acute effects of a selective nNOS inhibitor, S-methyl-L-thiocitrulline (SMTC), on cerebral blood flow and brain functional connectivity in healthy human volunteers (n=19). We performed a randomised, placebo-controlled, crossover study with either intravenous SMTC or placebo, using magnetic resonance imaging protocols with arterial spin labelling and functional resting state neuroimaging. Conclusions These data suggest a fundamental physiological role of nNOS in regulating regional cerebral blood flow and functional connectivity in the human hippocampus. Our findings have relevance to the role of nNOS in the regulation of cerebral perfusion in health and disease. Translational Perspective Animal models have implicated dysfunctional nNOS-mediated signaling in neurovascular and neurodegenerative conditions. This first study of the effects of a selective nNOS inhibitor, S-methyl-thiocitrulliune (SMTC), on the physiological regulation of human cerebral blood flow and brain functional connectivity opens the way to investigation of the effects of nNOS in cerebrovascular disease states. We also demonstrate that an acute infusion of SMTC is safe yet biologically active within the healthy human brain. The therapeutic potential of modulating the nNOS pathway in the brain could now be investigated; e.g. whether inhibition of nNOS activity is valuable in settings of post-ischemia excitotoxicity.

scholarly journals Feedback Control of Glomerular Vascular Tone in Neuronal Nitric Oxide Synthase Knockout Mice

2001 ◽  
Vol 12 (8) ◽  
pp. 1599-1606
Author(s):  
VOLKER VALLON ◽  
TIMOTHY TRAYNOR ◽  
LUCIANO BARAJAS ◽  
YUNING G. HUANG ◽  
JOSIE P. BRIGGS ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Nitric Oxide Synthase ◽  
Knockout Mice ◽  
Neuronal Nitric Oxide Synthase ◽  
Distal Tubule ◽  
Flow Pressure ◽  
Oxide Synthase ◽  
Stop Flow

Abstract. For further elucidation of the role of neuronal nitric oxide synthase (nNOS) in macula densa (MD) cells, experiments were performed in anesthetized nNOS knockout mice (nNOS -/-). At comparable levels of arterial BP, renal blood flow was not significantly different between nNOS +/+ and nNOS -/- (1.7 ± 0.2 versus 1.4 ± 0.1 ml/min), and autoregulation of renal blood flow was maintained to a pressure level of approximately 85 mmHg in both groups of mice (n = 6 in each group). The fall in proximal tubular stop-flow pressure in response to an increase in loop of Henle perfusion rate from 0 to 30 nl/min was comparable in nNOS +/+ and -/- mice (40.7 ± 1.6 to 32 ± 2 mmHg versus 40.6 ± 1.6 to 31.6 ± 2 mmHg; not significant; n = 13 versus 18 nephrons). Luminal application of the nonselective NOS inhibitor nitro-L-arginine (10-3 and 10-2 M) enhanced the perfusion-dependent fall in stop-flow pressure in nNOS +/+ (7 ± 1 to 13 ± 2 mmHg; P < 0.05) but not in nNOS -/- (7 ± 1 to 8 ± 1 mmHg; not significant) mice. nNOS -/- mice exhibited a lower nephron filtration rate, compared with nNOS +/+, during free-flow collections from early distal tubules (influence of MD intact, 7 ± 0.7 versus 10.9 ± 1 nl/min; P = 0.002) but not from late proximal tubule (influence of MD minimized, 10.1 ± 1 versus 11.7 ± 1 nl/min; not significant; n = 16 nephrons). Distal Cl concentration and fractional absorption of fluid or chloride up to the early distal tubule was not different between nNOS -/- and +/+ mice. The data indicate that nNOS in MD tonically attenuates the GFR-lowering influence of ambient luminal NaCl, which may serve to increase the fluid and electrolyte load to the distal tubule, consistent with a role of MD nNOS in tubuloglomerular feedback resetting.

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