scholarly journals Activation of Neuronal Nitric Oxide Release Inhibits Spontaneous Firing in Adult Gonadotropin-Releasing Hormone Neurons: A Possible Local Synchronizing Signal

Endocrinology ◽  
2007 ◽  
Vol 149 (2) ◽  
pp. 587-596 ◽  
Author(s):  
Jérôme Clasadonte ◽  
Pierre Poulain ◽  
Jean-Claude Beauvillain ◽  
Vincent Prevot
Keyword(s):  
Nitric Oxide ◽  
Neuronal Activity ◽  
Brain Slices ◽  
No Synthase ◽  
Membrane Properties ◽  
No Production ◽  
Spontaneous Firing ◽  
Preoptic Region ◽  
Gnrh Neurons ◽  
Bursting Activity

The activation of nitric oxide (NO) signaling pathways in hypothalamic neurons plays a key role in the control of GnRH secretion that is central to reproductive function. It is unknown whether NO directly modulates the firing behavior of GnRH neurons in the preoptic region of the mature brain. Using patch-clamp recordings from GnRH neurons expressing green fluorescent protein in adult mice brain slices, we demonstrate that the NO precursor, l-arginine (Arg), or the NO donor, diethylamine/NO, induced a robust and reversible reduction in the spontaneous firing activity of GnRH neurons, including bursting activity. The effects of l-Arg were prevented by the NO synthase inhibitor Nω-nitro-l-Arg methyl ester hydrochloride. Histochemical studies revealing a close anatomical relationship between neurons producing NO and GnRH perikarya, together with the loss of the l-Arg-mediated inhibition of GnRH neuronal activity via the selective blockade of neuronal NO synthase, suggested that the primary source of local NO production in the mouse preoptic region was neuronal. Synaptic transmission uncoupling did not alter the effect of NO, suggesting that NO affects the firing pattern of GnRH neurons by acting at a postsynaptic site. We also show that the NO-mediated changes in membrane properties in the GnRH neurons require soluble guanylyl cyclase activity and may involve potassium conductance. By revealing that NO is a direct modulator of GnRH neuronal activity, our results introduce the intriguing possibility that this gaseous neurotransmitter may be used by the sexual brain to modulate burst firing patterns. It may set into phase the bursting activity of GnRH neurons at key stages of reproductive physiology.

Decrease in ambient [Cl-] stimulates nitric oxide release from cultured rat mesangial cells

1994 ◽  
Vol 267 (1) ◽  
pp. F190-F195 ◽  
Author(s):  
H. Tsukahara ◽  
Y. Krivenko ◽  
L. C. Moore ◽  
M. S. Goligorsky
Keyword(s):  
Nitric Oxide ◽  
Mesangial Cells ◽  
Ionic Composition ◽  
Juxtaglomerular Apparatus ◽  
Cytosolic Calcium ◽  
No Synthase ◽  
Tubuloglomerular Feedback ◽  
No Production ◽  
Rapid Reduction ◽  
No Release

It has been hypothesized that fluctuations of the ionic composition in the interstitium of juxtaglomerular apparatus (JGA) modulate the function of extraglomerular mesangial cells (MC), thereby participating in tubuloglomerular feedback (TGF) signal transmission. We examined the effects of isosmotic reductions in ambient sodium concentration ([Na+]) and [Cl-] on cytosolic calcium concentration ([Ca2+]i) in cultured rat MC. Rapid reduction of [Na+] or [Cl-] in the bath induced a concentration-dependent rise in [Ca2+]i. MC are much more sensitive to decreases in ambient [Cl-] than to [Na+]; a decrease in [Cl-] as small as 14 mM was sufficient to elicit a detectable [Ca2]i response. These observations suggest that MC can be readily stimulated by modest perturbations of extracellular [Cl-]. Next, we examined whether activation of MC by lowered ambient [Cl-] influences cellular nitric oxide (NO) production. Using an amperometric NO sensor, we found that a 13 mM decrease in ambient [Cl-] caused a rapid, Ca2+/calmodulin-dependent rise in NO release from MC. This response was not inhibitable by dexamethasone, indicating the involvement of the constitutive rather than the inducible type of NO synthase in MC. In addition, the NO release was blunted by indomethacin pretreatment, suggesting that a metabolite(s) of cyclooxygenase regulates the activation of NO synthase in MC. Our findings that small perturbations in external [Cl-] stimulate MC to release NO, a highly diffusible and rapidly acting vasodilator, provide a possible mechanism to explain the transmission of the signal for the TGF response within the JGA.

Arginase inhibition increases nitric oxide production in bovine pulmonary arterial endothelial cells

2004 ◽  
Vol 287 (1) ◽  
pp. L60-L68 ◽  
Author(s):  
Louis G. Chicoine ◽  
Michael L. Paffett ◽  
Tamara L. Young ◽  
Leif D. Nelin
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
No Synthase ◽  
No Production ◽  
Urea Production ◽  
Pulmonary Arterial ◽  
Factor Α ◽  
Arterial Endothelial Cells ◽  
Regular Medium ◽  
Necrosis Factor

Nitric oxide (NO) is produced by NO synthase (NOS) from l-arginine (l-Arg). Alternatively, l-Arg can be metabolized by arginase to produce l-ornithine and urea. Arginase (AR) exists in two isoforms, ARI and ARII. We hypothesized that inhibiting AR with l-valine (l-Val) would increase NO production in bovine pulmonary arterial endothelial cells (bPAEC). bPAEC were grown to confluence in either regular medium (EGM; control) or EGM with lipopolysaccharide and tumor necrosis factor-α (L/T) added. Treatment of bPAEC with L/T resulted in greater ARI protein expression and ARII mRNA expression than in control bPAEC. Addition of l-Val to the medium led to a concentration-dependent decrease in urea production and a concentration-dependent increase in NO production in both control and L/T-treated bPAEC. In a second set of experiments, control and L/T bPAEC were grown in EGM, EGM with 30 mM l-Val, EGM with 10 mM l-Arg, or EGM with both 10 mM l-Arg and 30 mM l-Val. In both control and L/T bPAEC, treatment with l-Val decreased urea production and increased NO production. Treatment with l-Arg increased both urea and NO production. The addition of the combination l-Arg and l-Val decreased urea production compared with the addition of l-Arg alone and increased NO production compared with l-Val alone. These data suggest that competition for intracellular l-Arg by AR may be involved in the regulation of NOS activity in control bPAEC and in response to L/T treatment.

Functional difference between SP and NKA: relaxation of gastric muscle by SP is mediated by VIP and NO

1993 ◽  
Vol 264 (4) ◽  
pp. G678-G685
Author(s):  
J. G. Jin ◽  
S. Misra ◽  
J. R. Grider ◽  
G. M. Makhlouf
Keyword(s):  
Nitric Oxide ◽  
Circular Muscle ◽  
No Synthase ◽  
No Production ◽  
Neurokinin A ◽  
Functional Difference ◽  
Receptor Agonists ◽  
Gastric Muscle ◽  
Guinea Pig Stomach ◽  
Synthase Inhibitor

The mechanism of action of endogenous tachykinins [substance P (SP) and neurokinin A and B (NKA and NKB)] and of receptor-specific tachykinin analogues (SP methyl ester (SPME), [beta-Ala8]NKA-(4-10), and senktide) was examined in circular muscle of guinea pig stomach. Cross-desensitization studies confirmed that SPME and SP interacted with NK-1 receptors, [beta-Ala8]NKA-(4-10) and NKA with NK-2 receptors, and senktide and NKB with NK-3 receptors. NK-1 and NK-3-receptor agonists induced relaxation and stimulated vasoactive intestinal peptide (VIP) release and nitric oxide (NO) production: tetrodotoxin abolished VIP release, NO production, and relaxation, converting the response to NK-1-receptor agonists to contraction; the NO synthase inhibitor NG-nitro-L-arginine (L-NNA) abolished NO production, partly inhibited VIP release (56-64%, P < 0.01), and abolished relaxation; the VIP antagonist VIP-(10-28) partly inhibited NO production (73-74%, P < 0.001) and relaxation (56-58%, P < 0.01); and atropine augmented relaxation by 28-35% (P < 0.01). The pattern of inhibition implied that: 1) relaxation was mediated by VIP and NO; 2) VIP release was partly dependent on NO production, since it was strongly inhibited by L-NNA; and 3) NO was largely produced by the action of VIP on muscle cells, since it was strongly inhibited by VIP-(10-28). NK-2-receptor agonists elicited only contraction that was not affected by tetrodotoxin; these agonists also inhibited VIP release, NO production, and relaxation induced by NK-1- and NK-3-receptor agonists.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

scholarly journals Luminal flow induces eNOS activation and translocation in the rat thick ascending limb

2004 ◽  
Vol 287 (2) ◽  
pp. F274-F280 ◽  
Author(s):  
Pablo A. Ortiz ◽  
Nancy J. Hong ◽  
Jeffrey L. Garvin
Keyword(s):  
Nitric Oxide ◽  
Apical Membrane ◽  
Renal Medulla ◽  
Cytochalasin D ◽  
No Synthase ◽  
No Production ◽  
Thick Ascending Limb ◽  
Loop Of Henle ◽  
Luminal Flow ◽  
Nos Inhibitor

Nitric oxide (NO) produced by endothelial NO synthase (eNOS) acts as an autacoid to inhibit NaCl absorption in the thick ascending limb of the loop of Henle (THAL). In the vasculature, shear stress activates eNOS. We hypothesized that increasing luminal flow activates eNOS and enhances NO production in the THAL. We measured NO production by isolated, perfused THALs using a NO-sensitive microelectrode. Increasing luminal flow from 0 to 20 nl/min increased NO production by 43.1 ± 4.1 pA/mm of tubule ( n = 10, P < 0.05), and this response was blunted (92%) by the NOS inhibitor l-ωnitro-methylarginine ( P < 0.05). We studied the effect of flow on eNOS subcellular localization. In the absence of flow, eNOS was diffusely localized throughout the cell (basolateral = 33 ± 4%; middle = 27 ± 3%; apical = 40 ± 4% of total eNOS). Increasing luminal flow induced eNOS translocation to the apical membrane, as evidenced by a 60% increase in eNOS immunoreactivity in the apical membrane (from 40 ± 4 to 65 ± 2%; n = 6; P < 0.05). Disrupting the actin cytoskeleton with cytochalasin D (10 μM) reduced flow-induced NO production by 62% (from 37.1 ± 3.4 to 14.0 ± 2.4 pA/mm tubule, n = 7, P < 0.04) and blocked flow-induced eNOS translocation. Flow also increased the amount of phosphorylated eNOS (Ser1179) at the apical membrane (from 25 ± 2 to 56 ± 2%; P < 0.05). We conclude that increasing luminal flow induces eNOS activation and translocation to the apical membrane in THALs. These are the first data showing that flow regulates eNOS in epithelial cells. This may be an important mechanism for regulation of NO levels in the renal medulla.

17β-Estradiol decreases hypoxic induction of erythropoietin gene expression

2002 ◽  
Vol 283 (2) ◽  
pp. R496-R504 ◽  
Author(s):  
Harshini Mukundan ◽  
Thomas C. Resta ◽  
Nancy L. Kanagy
Keyword(s):  
Gene Expression ◽  
Nitric Oxide ◽  
Oxygen Delivery ◽  
Chronic Hypoxia ◽  
No Synthase ◽  
No Production ◽  
Enos Expression ◽  
Hypoxic Induction ◽  
Endothelial No Synthase ◽  
17Β Estradiol

Exposure to chronic hypoxia induces erythropoietin (EPO) production to facilitate oxygen delivery to hypoxic tissues. Previous studies from our laboratory found that ovariectomy (OVX) exacerbates the polycythemic response to hypoxia and treatment with 17β-estradiol (E2-β) inhibits this effect. We hypothesized that E2-β decreases EPO gene expression during hypoxia. Because E2-β can induce nitric oxide (NO) production and NO can attenuate EPO synthesis, we further hypothesized that E2-β inhibition of EPO gene expression is mediated by NO. These hypotheses were tested in OVX catheterized rats treated with E2-β (20 μg/day) or vehicle for 14 days and exposed to 8 or 12 h of hypoxia (12% O2) or normoxia. We found that E2-β treatment significantly decreased EPO synthesis and gene expression during hypoxia. E2-β treatment did not induce endothelial NO synthase (eNOS) expression in the kidney but potentiated hypoxia-induced increases in plasma nitrates. We conclude that E2-β decreases hypoxic induction of EPO. However, this effect does not appear to be related to changes in renal eNOS expression.

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.

Regulation of Ca(2+)-dependent nitric oxide synthase in bovine aortic endothelial cells

1995 ◽  
Vol 269 (3) ◽  
pp. C757-C765 ◽  
Author(s):  
B. J. Buckley ◽  
Z. Mirza ◽  
A. R. Whorton
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
No Synthase ◽  
No Production ◽  
Intact Cells ◽  
Aortic Endothelial Cells ◽  
A 23187 ◽  
Transient Rise ◽  
Synthase Inhibitor ◽  
Sustained Increase

Vascular endothelium responds to Ca(2+)-mobilizing agonists by producing nitric oxide (NO), a potent vasodilator and inhibitor of platelet aggregation. Regulation of constitutively expressed endothelial NO synthase (eNOS) in intact cells is not well understood. We investigated the kinetics of NO formation in response to Ca(2+)-mobilizing agonists, the requirement for extracellular L-arginine, and the role of NO in regulating eNOS activity. When endothelial cells were stimulated with bradykinin and ATP in the presence of 100 microM L-arginine, we observed a rapid and transient rise in intracellular Ca2+ concentration ([Ca2+]i) from 50 +/- 8 nM to 698 +/- 74 and 637 +/- 53 nM, respectively, and a rapid and transient rise in NO production from a basal level of 37 pmol.min-1.mg protein-1 to 256 and 275 pmol.min-1.mg protein-1, respectively. When cells were stimulated with A-23187 or thapsigargin in the presence of 100 microM L-arginine, we observed a sustained increase in [Ca2+]i and a sustained increase in NO production. The rate of NO synthesis was linear over 30 min, rising above control levels of 7 pmol/min to 53 pmol/min for A-23187 and 62 pmol/min for thapsigargin. Thapsigargin stimulated NO production and [Ca2+]i with 50% effective concentration values of 0.01 and 0.05 microM, respectively. Ca(2+)-stimulated NO production was attenuated by the NO synthase inhibitor NG-monomethyl-L-arginine, the removal of extracellular L-arginine, and the Ca(2+)-chelator ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid. When we exposed cells to NO gas (3.1 mM for 15 min) and S-nitrosoglutathione (10 mM for 1 h) thapsigargin-stimulated NO production was decreased by 50%.(ABSTRACT TRUNCATED AT 250 WORDS)

Regulation of prostanoid vasomotor effects and receptors in choroidal vessels of newborn pigs

1997 ◽  
Vol 272 (3) ◽  
pp. R995-R1001 ◽  
Author(s):  
D. Abran ◽  
D. R. Varma ◽  
S. Chemtob
Keyword(s):  
Nitric Oxide ◽  
No Synthase ◽  
No Production ◽  
Camp Production ◽  
Nitrite Oxidation ◽  
Vascular Effects ◽  
Inositol 1,4,5 Trisphosphate ◽  
Newborn Pigs ◽  
Synthase Inhibitor ◽  
Choroidal Vessels

This study was conducted to determine if high perinatal prostaglandin (PG) and thromboxane (TxA2) levels modified their choroidal vasomotor effects and receptor levels. Both nonperfused (eyecup preparations) and perfused choroidal vessels from saline- or ibuprofen-treated 1-day-old pigs and tissues from adult pigs were used; all prostanoids produced similar vasomotor effects on both preparations. Choroidal PGF2alpha, TxA2, PGI2, and PGD2 levels were higher in the newborn than in adult pigs; injections of ibuprofen (40 mg/kg every 4 h for 48 h) into newborn pigs significantly decreased choroidal levels of all these prostanoids. PGF2alpha and the TxA2 mimetic U-46619 caused less choroidal vasoconstriction and production of inositol 1,4,5-trisphosphate (IP3) in the newborn than in adult pigs. Ibuprofen treatment increased choroidal PGF2alpha vasoconstrictor effects, IP3 production, and receptors, but did not modify response to U-46619. Carbaprostacyclin (PGI2 analog) caused a greater choroidal vasodilatation and adenosine adenosine 3',5'-cyclic monophosphate (cAMP) production in the newborn than in adult pigs; these effects were not modified by ibuprofen. PGD2 did not increase cAMP but caused greater dilatation and nitrite [oxidation product of nitric oxide (NO)] production in the choroid of newborn than of adult pigs, which were decreased to adult levels by ibuprofen and the NO synthase inhibitor N(omega)-nitro-L-arginine. These data suggest that high perinatal PG levels downregulate PGF2alpha receptors and vascular effects but do not modify choroidal responses to TxA2 and PGI2; NO seems to contribute to the vasodilator effects of PGD2.

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