scholarly journals Lactate dilates cochlear capillaries via type V fibrocyte-vessel coupling signaled by nNOS

2011 ◽  
Vol 301 (4) ◽  
pp. H1248-H1254 ◽  
Author(s):  
Min Dai ◽  
Yue Yang ◽  
Xiaorui Shi
Keyword(s):  
Blood Flow ◽  
Inner Ear ◽  
Regional Blood Flow ◽  
High Energy ◽  
No Synthase ◽  
Monocarboxylate Transporter ◽  
No Production ◽  
Spiral Ligament ◽  
Monocarboxylate Transporter 1 ◽  
Type V

Transduction of sound in the inner ear demands tight control over delivery of oxygen and glucose. However, the mechanisms underlying the control of regional blood flow are not yet fully understood. In this study, we report a novel local control mechanism that regulates cochlear blood flow to the stria vascularis, a high energy-consuming region of the inner ear. We found that extracellular lactate had a vasodilatory effect on the capillaries of the spiral ligament under both in vitro and in vivo conditions. The lactate, acting through monocarboxylate transporter 1 (MCT1), initiated neuronal nitric oxide (NO) synthase (nNOS) and catalyzed production of NO for the vasodilation. Blocking MCT1 with the MCT blocker, α-cyano-4-hydroxycinnamate (CHC), or a suppressing NO production with either the nonspecific inhibitor of NO synthase, NG-nitro-l-arginine methyl ester (l-NAME), or either of two selective nNOS inhibitors, 3-bromo-7-nitroindazole or (4S)- N-(4-amino-5[aminoethyl]aminopentyl)- N′-nitroguanidine (TFA), totally abolished the lactate-induced vasodilation. Pretreatment with the selective endothelial NO synthase inhibitor, l- N5-(1-iminoethyl)ornithine (l-NIO), eliminated the inhibition of lactate-induced vessel dilation. With immunohistochemical labeling, we found the expression of MCT1 and nNOS in capillary-coupled type V fibrocytes. The data suggest that type V fibrocytes are the source of the lactate-induced NO. Cochlear microvessel tone, regulated by lactate, is mediated by an NO-signaled coupling of fibrocytes and capillaries.

scholarly journals Nitric oxide production duringVibrio choleraeinfection

1997 ◽  
Vol 273 (5) ◽  
pp. G1160-G1167 ◽  
Author(s):  
Edward N. Janoff ◽  
Hiroshi Hayakawa ◽  
David N. Taylor ◽  
Claudine E. Fasching ◽  
Julie R. Kenner ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Epithelial Cells ◽  
Regional Blood Flow ◽  
Fluid Secretion ◽  
The United States ◽  
No Production ◽  
Loop Model ◽  
Ileal Loop

Vibrio cholerae induces massive intestinal fluid secretion that continues for the life of the stimulated epithelial cells. Enhanced regional blood flow and peristalsis are required to adapt to this obligatory intestinal secretory challenge. Nitric oxide (NO) is a multifunctional molecule that modulates blood flow and peristalsis and possesses both cytotoxic and antibacterial activity. We demonstrate that, compared with those in asymptomatic control subjects, levels of stable NO metabolites ([Formula: see text]/[Formula: see text]) are significantly increased in sera from acutely ill Peruvian patients with natural cholera infection as well as from symptomatic volunteers from the United States infected experimentally with V. cholerae. In a rabbit ileal loop model in vivo, cholera toxin (CT) elicited fluid secretion and dose-dependent increases in levels of[Formula: see text]/[Formula: see text]in the fluid ( P < 0.01). In contrast, lipopolysaccharide (LPS) elicited no such effects when applied to the intact mucosa. NO synthase (NOS) catalytic activity also increased in toxin-exposed tissues ( P< 0.05), predominantly in epithelial cells. The CT-induced NOS activity was Ca2+dependent and was not suppressed by dexamethasone. In conclusion, symptomatic V. cholerae infection induces NO production in humans. In the related animal model, CT, but not LPS, stimulated significant production of NO in association with increases in local Ca2+-dependent NOS activity in the tissues.

In vivo assessment of microvascular nitric oxide production and its relation with blood flow

2001 ◽  
Vol 280 (3) ◽  
pp. H1222-H1231 ◽  
Author(s):  
X. F. Figueroa ◽  
A. D. Martínez ◽  
D. R. González ◽  
P. I. Jara ◽  
S. Ayala ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Plasma Flow ◽  
Subcellular Fractionation ◽  
No Synthase ◽  
Cheek Pouch ◽  
No Production ◽  
Hamster Cheek Pouch ◽  
Membrane Bound

To assess the hypothesis that microvascular nitric oxide (NO) is critical to maintain blood flow and solute exchange, we quantified NO production in the hamster cheek pouch in vivo, correlating it with vascular dynamics. Hamsters (100–120 g) were anesthetized and prepared for measurement of microvessel diameters by intravital microscopy, of plasma flow by isotopic sodium clearance, and of NO production by chemiluminescence. Analysis of endothelial NO synthase (eNOS) location by immunocytochemistry and subcellular fractionation revealed that eNOS was present in arterioles and venules and was 67 ± 7% membrane bound. Basal NO release was 60.1 ± 5.1 pM/min ( n = 35), and plasma flow was 2.95 ± 0.27 μl/min ( n = 29). Local NO synthase inhibition with 30 μM N ω-nitro-l-arginine reduced NO production to 8.6 ± 2.6 pmol/min (−83 ± 5%, n = 9) and plasma flow to 1.95 ± 0.15 μl/min (−28 ± 12%, n = 17) within 30–45 min, in parallel with constriction of arterioles (9–14%) and venules (19–25%). The effects of N ω-nitro-l-arginine (10–30 μM) were proportional to basal microvascular conductance ( r = 0.7, P < 0.05) and fully prevented by 1 mM l-arginine. We conclude that in this tissue, NO production contributes to 35–50% of resting microvascular conductance and plasma-tissue exchange.

Regional blood flow and skeletal muscle energy status in endotoxemic rats

1987 ◽  
Vol 252 (5) ◽  
pp. E581-E587 ◽  
Author(s):  
M. M. Jepson ◽  
M. Cox ◽  
P. C. Bates ◽  
N. J. Rothwell ◽  
M. J. Stock ◽  
...  
Keyword(s):  
Blood Flow ◽  
Protein Synthesis ◽  
Regional Blood Flow ◽  
High Energy ◽  
Whole Body ◽  
Sublethal Dose ◽  
Resonance Spectroscopy ◽  
High Energy Phosphates ◽  
Energy Status ◽  
Brown Adipose

Endotoxins induce muscle wasting in part as a result of depressed protein synthesis. To investigate whether these changes reflect impaired energy transduction, blood flow, O2 extraction, and high-energy phosphates in muscle and whole-body O2 consumption (VO2) have been measured. VO2 was measured for 6h after an initial sublethal dose of endotoxin (Escherichia coli lipopolysaccharide 0.3 mg/100 g body wt sc) or saline and during 6h after a second dose 24 h later. In fed or fasted rats, VO2 was either increased or better maintained after endotoxin. In anesthetized fed rats 3-4 after the second dose of endotoxin VO2 was increased, and this was accompanied by increased blood flow to liver (hepatic arterial supply), kidney, and perirenal brown adipose tissue and a 57 and 64% decrease in flow to back and hindlimb muscle, respectively, with no change in any other organ. Hindlimb arteriovenous O2 was unchanged, indicating markedly decreased aerobic metabolism in muscle, and the contribution of the hindlimb to whole-body VO2 decreased by 46%. Adenosine 5'-triphosphate levels in muscle were unchanged in endotoxin-treated rats, and this was confirmed by topical nuclear magnetic resonance spectroscopy, which also showed muscle pH to be unchanged. These results show that although there is decreased blood flow and aerobic oxidation in muscle, adenosine 5'-triphosphate availability does not appear to be compromised so that the endotoxin-induced muscle catabolism and decreased protein synthesis must reflex some other mechanism.

scholarly journals Endogenous vascular remodeling in ischemic skeletal muscle: a role for nitric oxide

2003 ◽  
Vol 94 (3) ◽  
pp. 935-940 ◽  
Author(s):  
John B. Buckwalter ◽  
Valerie C. Curtis ◽  
Zoran Valic ◽  
Stephen B. Ruble ◽  
Philip S. Clifford
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Blood Flow ◽  
Methyl Ester ◽  
Vascular Remodeling ◽  
Treated Group ◽  
No Synthase ◽  
No Production ◽  
Ischemic Limb ◽  
Time Flow

To test the hypothesis that nitric oxide (NO) production is essential for endogenous vascular remodeling in ischemic skeletal muscle, 22 New Zealand White rabbits were chronically instrumented with transit-time flow probes on the common iliac arteries and underwent femoral ligation to produce unilateral hindlimb ischemia. Iliac blood flow and arterial pressure were recorded at rest and during a graded exercise test. An osmotic pump connected to a femoral arterial catheter continuously delivered N-nitro-l-arginine methyl ester (a NO synthase inhibitor) or a control solution ( N-nitro-d-arginine methyl ester or phenylephrine) to the ischemic limb over a 2-wk period. At 1, 3, and 6 wk after femoral ligation, maximal treadmill exercise blood flow in the ischemic limb was reduced compared with baseline in each group. However, maximal exercise blood flow was significantly ( P < 0.05) lower in the l-NAME-treated group than in controls for the duration of the study: 48 ± 4 vs. 60 ± 5 ml/min at 6 wk. Consistent with the reduction in maximal blood flow response, the duration of voluntary exercise was also substantially ( P < 0.05) shorter in thel-NAME-treated group: 539 ± 67 vs. 889 ± 87 s. Resting blood flow was unaffected by femoral ligation in either group. The results of this study show that endogenous vascular remodeling, which partially alleviated the initial deficit in blood flow, was interrupted by NO synthase inhibition. Therefore, we conclude that NO is essential for endogenous collateral development and angiogenesis in ischemic skeletal muscle in the rabbit.

Intracoronary intermedin 1–47 augments cardiac perfusion and function in anesthetized pigs: role of calcitonin receptors and β-adrenoreceptor-mediated nitric oxide release

2009 ◽  
Vol 107 (4) ◽  
pp. 1037-1050 ◽  
Author(s):  
Elena Grossini ◽  
Claudio Molinari ◽  
David A. S. G. Mary ◽  
Francesca Uberti ◽  
Philippe Primo Caimmi ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Cardiac Function ◽  
Coronary Blood Flow ◽  
No Synthase ◽  
Cardiac Response ◽  
No Production ◽  
Receptor Complexes ◽  
Arterial Blood

Systemic intermedin (IMD)1–47 administration has been reported to result in vasodilation and marked hypotension through calcitonin-related receptor complexes. However, its effects on the coronary circulation and the heart have not been examined in vivo. The present study was therefore planned to determine the primary in vivo effect of IMD1–47 on coronary blood flow and cardiac function and the involvement of the autonomic nervous system and nitric oxide (NO). In 35 anesthetized pigs, IMD1–47, infused into the left anterior descending coronary artery at doses of 87.2 pmol/min, at constant heart rate and arterial blood pressure, augmented coronary blood flow and cardiac function. These responses were graded in a further five pigs by increasing the infused dose of IMD1–47 between 0.81 and 204.1 pmol/min. In the 35 pigs, the blockade of cholinergic receptors (intravenous atropine, 5 pigs), α-adrenoceptors (intravenous phentolamine, 5 pigs), and β1-adrenoceptors (intravenous atenolol, 5 pigs) did not abolish the cardiac response to IMD1–47, the effects of which were prevented by blockade of β2-adrenoceptors (intravenous butoxamine, 5 pigs), NO synthase (intracoronary Nω-nitro-l-arginine methyl ester, 5 pigs), and calcitonin-related receptors (intracoronary CGRP8–37/AM22–52, 10 pigs). In porcine coronary endothelial cells, IMD1–47 induced the phosphorylation of endothelial NO synthase and NO production through cAMP signaling leading to ERK, Akt, and p38 activation, which was prevented by the inhibition of β2-adrenoceptors, calcitonin-related receptor complexes, and K+ channels. In conclusion, IMD1–47 primarily augmented coronary blood flow and cardiac function through the involvement of calcitonin-related receptor complexes and β2-adrenoreceptor-mediated NO release. The intracellular signaling involved cAMP-dependent activation of kinases and the opening of K+ channels.

scholarly journals Functional expression of P2X4 receptor in capillary endothelial cells of the cochlear spiral ligament and its role in regulating the capillary diameter

2011 ◽  
Vol 301 (1) ◽  
pp. H69-H78 ◽  
Author(s):  
T. Wu ◽  
M. Dai ◽  
X. R. Shi ◽  
Z. G. Jiang ◽  
A. L. Nuttall
Keyword(s):  
Endothelial Cells ◽  
Blood Flow ◽  
Pyridoxal Phosphate ◽  
Regional Blood Flow ◽  
Reversal Potential ◽  
Lateral Wall ◽  
Disulfonic Acid ◽  
Spiral Ligament ◽  
Dependent Manner ◽  
P2x4 Receptor

The cochlear lateral wall generates the endocochlear potential (EP), which creates a driving force for the hair cell transduction current and is essential for normal hearing. Blood flow at the cochlear lateral wall is critically important for maintaining the EP. The vulnerability of the EP to hypoxia suggests that the blood flow in the cochlear lateral wall is dynamically and precisely regulated to meet the changing metabolic needs of the cochlear lateral wall. It has been reported that ATP, an important extracellular signaling molecule, plays an essential role in regulating cochlear blood flow. However, the cellular mechanism underlying ATP-induced regional blood flow changes has not been investigated. In the current study, we demonstrate that 1) the P2X4 receptor is expressed in endothelial cells (ECs) of spiral ligament (SL) capillaries. 2) ATP elicits a characteristic current through P2X4 on ECs in a dose-dependent manner (EC50 = 0.16 mM). The ATP current has a reversal potential at ∼0 mV; is inhibited by 5-(3-bromophenyl)-1,3-dihydro-2 H-benzofuro[3,2- e]-1,4-diazepin-2-one (5-BDBD), LaCl3, pyridoxal phosphate-6-azo(benzene-2,4-disulfonic acid) tetrasodium salt hydrate (PPADS), and extracellular acidosis; and is less sensitive to α,β-methyleneadenosine 5′-triphosphate (α,β-MeATP) and 2′- and 3′- O-(4-benzoyl-benzoyl) adenosine 5′-triphosphate (BzATP). 3) ATP elicits a transient increase of intracellular Ca2+ in ECs. 4) In accordance with the above in vitro findings, perilymphatic ATP (1 mM) caused dilation in SL capillaries in vivo by 11.5%. Nω-nitro-l-arginine methyl ester hydrochloride (l-NAME), a nonselective inhibitor of nitric oxide synthase, or 5-BDBD, the specific P2X4 inhibitor, significantly blocked the dilation. These findings support our hypothesis that extracellular ATP regulates cochlear lateral blood flow through P2X4 activation in ECs.

P-450 epoxygenase and NO synthase inhibitors reduce cerebral blood flow response toN-methyl-d-aspartate

2000 ◽  
Vol 279 (4) ◽  
pp. H1616-H1624 ◽  
Author(s):  
Anish Bhardwaj ◽  
Frances J. Northington ◽  
Juan R. Carhuapoma ◽  
John R. Falck ◽  
David R. Harder ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Nmda Receptor ◽  
Receptor Activation ◽  
No Synthase ◽  
Receptor Subtype ◽  
No Production ◽  
Arginine Infusion ◽  
Flow Response ◽  
Substrate Inhibitor

Epoxyeicosatrienoic acids are cerebral vasodilators produced in astrocytes by cytochrome P-450 epoxygenase activity. The P-450 inhibitor miconazole attenuates the increase in cerebral blood flow (CBF) elicited by glutamate. We evaluated whether epoxygenase activity is involved in the CBF response to activation of the N-methyl-d-aspartate (NMDA) receptor subtype by using two structurally distinct inhibitors, miconazole and N-methylsulfonyl-6-(2-propargyloxyphenyl) hexanamide (MS-PPOH), a selective epoxygenase substrate inhibitor. Drugs were delivered locally through microdialysis probes in striata of anesthetized rats. Local CBF was measured by hydrogen clearance and compared with CBF in contralateral striatum receiving vehicle. Microdialysis perfusion of NMDA doubled CBF and increased nitric oxide (NO) production estimated by recovery of labeled citrulline in the dialysate during labeled arginine infusion. Perfusion of miconazole or MS-PPOH blocked the increase in CBF without decreasing citrulline recovery. Perfusion of N ω-nitro-l-arginine decreased baseline CBF and inhibited the CBF response to NMDA. Perfusion of MS-PPOH did not inhibit the CBF response to sodium nitroprusside. We conclude that both the P-450 epoxygenase and NO synthase pathways are involved in the local CBF response to NMDA receptor activation, and that the signaling pathway may be more complex than simply NO diffusion from neurons to vascular smooth muscle.

scholarly journals The mRNA and protein expression of ruminal MCT1 is increased by feeding a mixed hay/concentrate diet compared with hay <i>ad libitum</i> diet (Short Communication)

2011 ◽  
Vol 54 (3) ◽  
pp. 280-286 ◽  
Author(s):  
J. Kuzinski ◽  
M. Röntgen
Keyword(s):  
Protein Expression ◽  
Flow Cytometric Analysis ◽  
High Energy ◽  
Functional Adaptation ◽  
Monocarboxylate Transporter ◽  
Monocarboxylate Transporter 1 ◽  
Rumen Epithelium ◽  
Flow Cytometric ◽  
Mrna And Protein Expression ◽  
Ad Libitum

Abstract. In this study the protein and mRNA expression of Monocarboxylate transporter 1 (MCT1) was evaluated in rumen epithelial cells (REC) obtained from sheep fed hay ad libitum (control, h diet, n=4) or a mixed hay/concentrate diet (h/c diet, n=4) for two weeks. REC were isolated via fractionated trypsination and three groups consisting of fractions 3 to 5=G1, fractions 6 to 8=G2, and fractions 9 and 10=G3 were formed. Using an anti-basal cytokeratin antibody and flow cytometric analysis, the proportion of REC originating from the stratum basale (SB) was determined for each group. In addition, MCT1 mRNA and protein expression was determined by qRT-PCR and Western blot, respectively. Feeding the h/c diet led to a 299±93 % elevation of the number of SB cells known to express the MCT1 protein. This is accompanied by an increased MCT1 mRNA (1.8 to 2.2-fold) and protein (1.3-fold) expression. Thus, an increased number of MCT1 expressing cells and upregulation of ruminal MCT1 protein seem to be components of rumen epithelium functional adaptation to high energy diet.

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