scholarly journals Effect of nitric oxide on rat adrenal zona fasciculata steroidogenesis

1998 ◽  
Vol 158 (2) ◽  
pp. 197-203 ◽  
Author(s):  
CB Cymeryng ◽  
LA Dada ◽  
EJ Podesta
Keyword(s):  
Nitric Oxide ◽  
Inhibitory Effect ◽  
Adrenocortical Function ◽  
Zona Fasciculata ◽  
Dependent Manner ◽  
Adrenal Cells ◽  
Corticosterone Secretion ◽  
Adrenal Zona Fasciculata ◽  
Dose Dependent

The present study was designed to investigate the role of nitric oxide (NO) in the regulation of adrenocortical function. Different NO donors, such as sodium nitroprusside (SNP), S-nitroso-L-acetyl penicillamine, diethylamine/NO complex sodium salt and diethylenetriamine NO adduct, significantly decreased corticosterone production both in unstimulated and in corticotropin-stimulated zone fasciculata adrenal cells, in a dose-dependent manner. The effect of SNP was reversed by ferrous hemoglobin. A selective inhibitor of NO synthase, L-NG-nitro-arginine significantly increased corticosterone secretion. The effect of SNP was not mediated by cGMP as permeable cGMP analogs did not reproduce its inhibitory effect. SNP significantly inhibited the steroidogenesis stimulated by 8Br-cAMP and 22(R)-OH-cholesterol, but was ineffective when corticosterone was produced in the presence of exogenously added pregnenolone. Moreover, the conversion of [3H]cholesterol to [3H]pregnenolone and the production of pregnenolone or progesterone (assessed by RIA) were significantly decreased by SNP. Taken together, these results suggest that NO may be a negative modulator of adrenal zona fasciculata steroidogenesis.

The role of nitric oxide derived from l-arginine in the control of steroidogenesis, and perfusion medium flow rate in the isolated perfused rat adrenal gland

1993 ◽  
Vol 139 (3) ◽  
pp. 415-423 ◽  
Author(s):  
L. A. Cameron ◽  
J. P. Hinson
Keyword(s):  
Nitric Oxide ◽  
Adrenal Gland ◽  
Flow Rate ◽  
Adrenocortical Function ◽  
No Production ◽  
Percentage Increase ◽  
Perfusion Medium ◽  
Corticosterone Secretion ◽  
Dose Dependent

ABSTRACT The present studies were designed to investigate the role of nitric oxide (NO) in the regulation of adrenocortical function, using the intact rat adrenal gland in situ, perfused with medium (Hank's balanced salt solution) containing a range of concentrations of l-arginine, the substrate for NO production. In addition, the effects of NG-nitro-l-arginine methylester (l-NAME), an inhibitor of NO production, were investigated. Results showed that l-arginine caused a dose-dependent increase in the flow rate of the perfusion medium through the adrenal gland. This effect was specific, as neither d-arginine nor l-lysine had an effect. The presence of l-NAME (5 mmol/l) in perfusion medium containing l-arginine caused a decrease in flow rate to levels seen in the absence of l-arginine. In the presence of concentrations of l-arginine up to 500 μmol/l, corticosterone secretion rates were also stimulated in a dose-dependent manner. Further studies, investigating the effect of l-arginine on the response to ACTH(1–24) stimulation, found that the percentage increase in flow rate, aldosterone secretion and corticosterone secretion caused by ACTH were not significantly different using media containing 230 μmol l-arginine/l or in the absence of l-arginine. These results suggest a role for NO derived from l-arginine in the regulation of basal levels of adrenal vascular tone in the rat isolated adrenal gland preparation. They do not suggest an obligatory role for NO in either the vascular or steroidogenic response to ACTH stimulation. Journal of Endocrinology (1993) 139, 415–423

Evidence for lack of a role of cGMP in effect of alpha-hANP on aldosterone inhibition

1987 ◽  
Vol 252 (5) ◽  
pp. E643-E647 ◽  
Author(s):  
H. Matsuoka ◽  
M. Ishii ◽  
Y. Hirata ◽  
K. Atarashi ◽  
T. Sugimoto ◽  
...  
Keyword(s):  
Inhibitory Effect ◽  
Minor Role ◽  
Dependent Manner ◽  
Free Medium ◽  
Adrenal Cells ◽  
Aldosterone Production ◽  
A Minor ◽  
Dose Dependent ◽  
Derivatives Of

To investigate the role of guanosine 3',5'-cyclic monophosphate (cGMP) in the inhibitory effect on aldosterone production of alpha-human atrial natriuretic polypeptide (alpha-hANP) we first compared the effects of the peptide with those of sodium nitroprusside (SNP) on the production of aldosterone and cGMP in dispersed adrenal capsular cells of rats, second, examined the effects of derivatives of cGMP on the production of aldosterone, and, third, studied the influence of potassium on the effects of alpha-hANP on the production of aldosterone and cGMP. alpha-hANP at concentrations of 3 X 10(-8) to 3 X 10(-7) M decreased the production of aldosterone in a dose-dependent manner, while markedly increasing the production of cGMP. On the other hand, although SNP at concentrations of 10(-5) to 10(-3) M increased the production of cGMP in a dose-dependent manner, it caused no significant changes in the production of aldosterone. Neither dibutyryl cGMP nor 8-bromo-cGMP affected the production of aldosterone in the adrenal cells. Although the aldosterone-inhibitory effect of alpha-hANP was lost in the potassium-free medium, the cGMP-stimulatory effect of the peptide was not altered by adding potassium to the incubation medium at concentrations of 0-5 meq/l. These results suggest that cGMP plays a minor role in the inhibitory effect of alpha-hANP on the production of aldosterone and that the production of cGMP stimulated by the peptide is not directly involved in the decrease in aldosterone production in adrenal capsular cells of rats.

Role Of Cyclic Amp In The Inhibition Of Human Platelet Functions By Quercetin, A Flav0N0Id That Potentiates PGI2 Effect

1981 ◽  
Author(s):  
J P Cazenave ◽  
A Beretz ◽  
A Stierlé ◽  
R Anton
Keyword(s):  
Maximum Level ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Pde Inhibitors ◽  
Pde Inhibition ◽  
Induced Aggregation ◽  
Camp Levels ◽  
Dose Dependent

Injury to the endothelium (END) and subsequent platelet (PLAT)interactions with the subEND are important steps in thrombosis and atherosclerosis. Thus,drugs that protect the END from injury and also inhibit PLAT function are of interest. It has been shown that some flavonoids(FLA), a group of compounds found in plants, prevent END desquamation in vivo, inhibit cyclic nucleotide phosphodiesterases(PDE)and inhibit PLAT function. We have studied the structure-activity relationships of 13 purified FLA on aggregation and secretion of 14c-5HT of prelabeled washed human PLAT induced by ADP, collagen(COLL) and thrombin(THR). All the FLA were inhibitors of the 3 agents tested. Quercetin(Q), was the second best after fisetin. It inhibited secretion and aggregation with I50 of 330µM against 0.1 U/ML.THR, 102µM against 5µM ADP and 40 µM against COLL. This inhibitory effect is in the range of that of other PDE inhibitors like dipyridamole or 3-isobutyl-l- methylxanthine. The aggregation induced by ADP, COLL and THR is at least mediated by 3 mechanisms that can be inhibited by increasing cAMP levels. We next investigated if Q, which is a PDE inhibitor of bovine aortic microsomes,raises PLAT cAMP levels. cAMP was measured by a protein-binding method. ADP- induced aggregation(5µM) was inhibited by PGI2 (0.1 and 0.5 nM) . Inhibition was further potentiated(l.7 and 3.3 times) by lOµM Q, which alone has no effect on aggregation. The basal level of cAMP(2.2 pmol/108PLAT) was not modified by Q (50 to 500µM). Using these concentrations of Q,the rise in cAMP caused by PGI2(0.1 and 0.5nM) was potentiated in a dose dependent manner. Q potentiated the effect of PGI2 on the maximum level of cAMP and retarded its breakdown. Thus Q and possibly other FLA could inhibit the interaction of PLAT with the components of the vessel wall by preventing END damage and by inhibiting PLAT function through a rise in cAMP secondary to PDE inhibition and potentiation of the effect of vascular PGI2 on PLAT adenylate cyclase.

Role of Nitric Oxide towards Vasodilator Effects of Substance P and ATP in Human Forearm Vessels

1997 ◽  
Vol 92 (2) ◽  
pp. 123-131 ◽  
Author(s):  
Masanari Shiramoto ◽  
Tsutomu Imaizumi ◽  
Yoshitaka Hirooka ◽  
Toyonari Endo ◽  
Takashi Namba ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Substance P ◽  
Sodium Nitroprusside ◽  
Forearm Blood Flow ◽  
Dependent Manner ◽  
Human Forearm ◽  
Before And After ◽  
Dose Dependent

1. It has been shown in animals that substance P as well as acetylcholine releases endothelium-derived nitric oxide and evokes vasodilatation and that ATP-induced vasodilatation is partially mediated by nitric oxide. The aim of this study was to examine whether vasodilator effects of substance P and ATP are mediated by nitric oxide in humans. 2. In healthy volunteers (n = 35), we measured forearm blood flow by a strain-gauge plethysmograph while infusing graded doses of acetylcholine, substance P, ATP or sodium nitroprusside into the brachial artery before and after infusion of NG-monomethyl-l-arginine (4 or 8 μmol/min for 5 min). In addition, we measured forearm blood flow while infusing substance P before and during infusion of l-arginine (10 mg/min, simultaneously), or before and 1 h after oral administration of indomethacin (75 mg). 3. Acetylcholine, substance P, ATP or sodium nitroprusside increased forearm blood flow in a dose-dependent manner. NG-Monomethyl-l-arginine decreased basal forearm blood flow and inhibited acetylcholine-induced vasodilatation but did not affect substance P-, ATP-, or sodium nitroprusside-induced vasodilatation. Neither supplementation of l-arginine nor pretreatment with indomethacin affected substance P-induced vasodilatation. 4. Our results suggest that, in the human forearm vessels, substance P-induced vasodilatation may not be mediated by either nitric oxide or prostaglandins and that ATP-induced vasodilatation may also not be mediated by nitric oxide.

Role of Intracellular Ca2+Stores in the Inhibitory Effect of Halothane on Airway Smooth Muscle Contraction 

1998 ◽  
Vol 89 (1) ◽  
pp. 165-173 ◽  
Author(s):  
Michiaki Yamakage ◽  
Shinji Kohro ◽  
Takashi Matsuzaki ◽  
Hideaki Tsuchida ◽  
Akoyoshi Namiki
Keyword(s):  
Smooth Muscle ◽  
Sarcoplasmic Reticulum ◽  
Airway Smooth Muscle ◽  
Muscle Tension ◽  
Inhibitory Effect ◽  
Intracellular Concentration ◽  
Dependent Manner ◽  
Release Channel ◽  
Dose Dependent

Background Halothane directly inhibits contraction of airway smooth muscle, mainly by decreasing the intracellular concentration of free Ca2+ ([Ca2+]i). The role of intracellular Ca2+ stores, sarcoplasmic reticulum, is still unclear. We investigated the role of sarcoplasmic reticulum in the inhibitory effect of halothane on contraction of airway smooth muscle by measuring [Ca2+]i and intracellular concentration of inositol 1,4,5-triphosphate ([IP3]i), a second messenger for release of Ca2+ from sarcoplasmic reticulum. Methods [Ca2+]i was monitored by measuring the 500-nm light emission ratio (F340/F380) of a Ca2+ indicator fura-2 with isometric tension of canine tracheal smooth muscle strip. During Ca2+-free conditions, carbachol (10(-5) M) was introduced with pretreatment of halothane (0-3%). During Ca2+-free conditions, 20 mM caffeine, a Ca2+-induced Ca2+ release channel opener, was introduced with or without halothane. We measured [IP3]i during exposure to carbachol and halothane by radioimmunoassay technique. Results Pretreatment with halothane significantly diminished carbachol-induced increases in [Ca2+]i by 77% and muscle tension by 83% in a dose-dependent manner. Simultaneous administration of halothane significantly enhanced caffeine-induced transient increases in [Ca2+]i and muscle tension in a dose-dependent manner, by 97% and 69%, respectively. Pretreatment with halothane abolished these responses. Rapid increase in [IP3]i produced by carbachol was significantly inhibited by 32% by halothane in a dose-dependent manner. Conclusions Halothane, during Ca2+-free conditions, inhibits transient contraction of airway smooth muscle induced by muscarinic receptor stimulation, mainly by attenuating the increase in [Ca2+]i. Depletion of Ca2+ from sarcoplasmic reticulum via Ca2+-induced Ca2+ release channels also may contribute to the attenuation of the increase in [Ca2+]i by halothane.

scholarly journals A Role of Fluoride on Free Radical Generation and Oxidative Stress in BV-2 Microglia Cells

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Xi Shuhua ◽  
Liu Ziyou ◽  
Yan Ling ◽  
Wang Fei ◽  
Guifan Sun
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Dependent Manner ◽  
Microglia Cell ◽  
The Central Nervous System ◽  
Radical Generation ◽  
Oxide Synthase ◽  
Cell Medium ◽  
Dose Dependent

The generation of ROS and lipid peroxidation has been considered to play an important role in the pathogenesis of chronic fluoride toxicity. In the present study, we observed that fluoride activated BV-2 microglia cell line by observing OX-42 expression in immunocytochemistry. Intracellular superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), reactive oxygen species (ROS), superoxide anions (O2∙-), nitric oxide synthase (NOS), nitrotyrosine (NT) and nitric oxide (NO), NOS in cell medium were determined for oxidative stress assessment. Our study found that NaF of concentration from 5 to 20 mg/L can stimuli BV-2 cells to change into activated microglia displaying upregulated OX-42 expression. SOD activities significantly decreased in fluoride-treated BV-2 cells as compared with control, and MDA concentrations and contents of ROS andO2∙-increased in NaF-treated cells. Activities of NOS in cells and medium significantly increased with fluoride concentrations in a dose-dependent manner. NT concentrations also increased significantly in 10 and 50 mg/L NaF-treated cells compared with the control cells. Our present study demonstrated that toxic effects of fluoride on the central nervous system possibly partly ascribed to activiting of microglia, which enhanced oxidative stress induced by ROS and reactive nitrogen species.

scholarly journals Effects of Nitric Oxide on Ovulation and Ovarian Steroidogenesis and Prostaglandin Production in the Rabbit*

Endocrinology ◽  
1997 ◽  
Vol 138 (9) ◽  
pp. 3630-3637 ◽  
Author(s):  
Jun Yamauchi ◽  
Toyohiko Miyazaki ◽  
Shinya Iwasaki ◽  
Ikuko Kishi ◽  
Masako Kuroshima ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Oocyte Maturation ◽  
Concomitant Administration ◽  
Dependent Manner ◽  
Ovarian Steroidogenesis ◽  
Follicle Rupture ◽  
Nos Inhibitors ◽  
Dose Dependent

Abstract Evidence supports the involvement of nitric oxide (NO) in ovarian physiology. The present study was undertaken to investigate the role of the NO/NO synthase (NOS) systems in ovulation, oocyte maturation, ovarian steroidogenesis, and PG production using in vitro perfused rabbit ovaries. The addition of the NOS inhibitors, aminoguanidine hemisulfate salt (AG) and N-omega-nitro-l-arginine methyl ester (L-NAME), to the perfusate inhibited the ovulation induced by hCG in a dose-dependent manner, whereas D-NAME had no significant effect. Neither AG nor L-NAME affected the hCG-induced meiotic maturation of the ovulated ova. The exogenous administration of the NO generator, sodium nitroprusside (NP), induced follicle rupture in the absence of gonadotropin, but did not induce oocyte maturation. Inhibition of endogenous NOS by AG and L-NAME resulted in a significant elevation in the production of estradiol (E2), but not of progesterone, stimulated by hCG. The concomitant administration of NP significantly reduced the AG-stimulated production of E2 by ovaries perfused in the presence of hCG, which suggests that NO down-regulates ovarian E2 synthesis. Ovarian production of PGE2 and PGF2α in response to hCG was significantly blocked by L-NAME, and exogenous administration of NP stimulated the production of PGs in the absence of gonadotropin. Significant correlations were observed between the ovulatory efficiencies and the production of PGs by rabbit ovaries perfused with or without L-NAME. In conclusion, the ovarian NO/NOS system is involved in follicle rupture during the ovulatory process. NO may induce follicle rupture in rabbit ovaries at least in part by the stimulation of PG production.

Antithrombotic role of nitric oxide in rats under physiological conditions

2004 ◽  
Vol 91 (01) ◽  
pp. 71-75 ◽  
Author(s):  
Mariko Okudaira ◽  
Yasuo Ontachi ◽  
Tomoe Mizutani ◽  
Mika Omote ◽  
Tomotaka Yoshida ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Hepatic Dysfunction ◽  
Thrombus Formation ◽  
Dependent Manner ◽  
Fibrin Deposition ◽  
Physiological Conditions ◽  
Synthase Inhibitor ◽  
Dose Dependent

SummaryAlthough sepsis-induced release of nitric oxide (NO) is known to have an antithrombotic effect, it is unknown if NO exerts this same effect under physiological conditions. We have therefore attempted to determine whether or not NO protects against thrombus formation in normal Wistar rats injected with various amounts (0.8, 4.0, 20.0 and 100mg/kg/4hr) of L-NAME (N (omega)-nitro-l-arginine methyl ester), an NO synthase inhibitor, via the tail vein. Plasma levels of D-dimer fragments of fibrin were significantly increased in rats receiving L-NAME (0.21±0.04, 0.22±0.05, 0.26±0.07, 0.59±0.17µg/mL, means±SE; p<0.05, 0.05, 0.05, 0.01: L-NAME 0.8, 4, 20, 100, respectively, compared with control levels: <0.06 µg/mL), and thrombin-antithrombin complex (TAT) levels were significantly increased in rats receiving 20mg/kg/4hr or greater doses of L-NAME (4.5±1.1, 4.7±1.4, 18.7±4.9, 42.5±4.0ng/mL, NS, NS, p<0.05, 0.01, respectively, compared with control levels: 3.8±1.2 ng/mL). Glomerular fibrin deposition was increased in a dose-dependent manner in rats receiving L-NAME (6.8±1.5, 13.9±1.6, 32.4±2.6, 49.2±5.2%, p<0.05, 0.05, 0.01, 0.01, respectively, compared with control levels: 0.0±0.0%). Renal dysfunction and hepatic dysfunction were observed in rats receiving 20mg/kg/4hr or greater, or 100mg/kg/4hr, doses of L-NAME, respectively. Mean blood pressure was also elevated in rats receiving L-NAME in a dose-dependent manner. These findings suggest that NO, in addition to regulating blood pressure, is involved in prevention of thrombus formation under physiological circumstances.

Inhibition of nitric oxide synthase produces hypothermia and depresses lipopolysaccharide fever

1996 ◽  
Vol 271 (2) ◽  
pp. R333-R338 ◽  
Author(s):  
T. E. Scammell ◽  
J. K. Elmquist ◽  
C. B. Saper
Keyword(s):  
Nitric Oxide ◽  
Low Dose ◽  
Dependent Manner ◽  
Febrile Response ◽  
Bolus Intravenous Injection ◽  
Nos Inhibitor ◽  
Oxide Synthase ◽  
Dose Dependent ◽  
Higher Doses

The labile gas nitric oxide (NO) mediates a wide variety of thermoregulatory processes including vasomotor control, brown fat thermogenesis, and neuroendocrine regulation. Additionally, during endotoxemia, NO modulates the release of cytokines and hypothalamic peptides. To determine the role of NO in thermoregulation and fever, we intravenously injected the NO synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME) and measured its effects on body temperature during normal thermoregulation and endotoxemia in awake, unrestrained rats. L-NAME produced a stereoselective, dose-dependent hypothermia that lasted up to 4 h after bolus intravenous injection. Intravenous lipopolysaccharide (LPS) produced fever in a dose-dependent manner, which was preceded by hypothermia at higher doses alpha-LPS. NOS inhibition reduced the febrile response to LPS and produced marked hypothermia with a low dose of LPS. These findings indicate that NO may play an important role in thermoregulation and suggest that NO is required for the production of fever.

Acetylcholine stimulates steroidogenesis in isolated frog adrenal gland through muscarinic receptors: evidence for a desensitization mechanism

1987 ◽  
Vol 113 (3) ◽  
pp. 339-348 ◽  
Author(s):  
M. Benyamina ◽  
F. Leboulenger ◽  
I. Lirhmann ◽  
C. Delarue ◽  
M. Feuilloley ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Muscarinic Receptors ◽  
Splanchnic Nerve ◽  
Adrenocortical Function ◽  
Muscarinic Agonist ◽  
Dependent Manner ◽  
Adrenal Cells ◽  
Kinetics Of ◽  
Dose Dependent

ABSTRACT The effect of cholinergic agonists on glucocorticoid and mineralocorticoid production by frog interrenal (adrenal) tissue was studied in vitro by means of continuous perifusion. Acetylcholine, at doses ranging from 1 to 100 μmol/l, stimulated both corticosterone and aldosterone output in a dose-dependent manner, with a half-maximal effective dose of 2·5 μmol/l. Corticosteroid production was also stimulated by muscarine (10 μmol/l). In contrast, neither nicotine nor nicotine bitartrate (1–100 μmol/l) enhanced corticosteroid biosynthesis. The kinetics of the response of adrenal cells to acetylcholine and muscarine were similar to those observed during angiotensin II stimulation. In particular, a significant reduction (20–40%) in the spontaneous level of corticosteroid production was recorded after the initial infusion of muscarinic agents, but no further decrease in the basal level occurred after a second cholinergic administration. The effect of acetylcholine was blocked by the muscarinic receptor antagonist atropine (10 μmol/l). These results indicate that acetylcholine can stimulate frog adrenocortical cells through muscarinic receptors. Repeated 20-min pulses of acetylcholine (50 μmol/l) or muscarine (10 μmol/l), given at one pulse per 130 min, resulted in a marked reduction in the secretory response to the second pulse. No reduction in the stimulatory effect of acetylcholine or muscarine was observed when a 6·5-h interval separated two 20-min infusions of the secretagogue. In contrast with these findings, iterative pulses of the muscarinic agonist pilocarpine (in the range 1–100 μmol/l) did not cause any desensitization. These data show that the neurotransmitter acetylcholine can modulate frog adrenocortical function and suggest that, in addition to more conventional regulators, i.e. ACTH and angiotensin II, the cholinergic endings of the splanchnic nerve might participate in the regulation of corticosteroid secretion, at least under some physiological conditions such as neurogenic stress. J. Endocr. (1987) 113, 339–348

Sign in / Sign up

Export Citation Format

Share Document