scholarly journals Chronic inhibition of nitric oxide synthase augments the ACTH response to exercise

2009 ◽  
Vol 296 (3) ◽  
pp. R728-R734 ◽  
Author(s):  
Ryan Jankord ◽  
Richard M. McAllister ◽  
Venkataseshu K. Ganjam ◽  
M. Harold Laughlin
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Hpa Axis ◽  
Acute Exercise ◽  
Plasma Concentrations ◽  
Exercise Stress ◽  
Miniature Swine ◽  
Arterial Blood ◽  
Oxide Synthase ◽  
Response To Exercise

Exercise can activate the hypothalamo-pituitary-adrenocortical (HPA) axis, and regular exercise training can impact how the HPA axis responds to stress. The mechanism by which acute exercise induces HPA activity is unclear. Therefore, the purpose of this study was to test the hypothesis that nitric oxide modulates the neuroendocrine component of the HPA axis during exercise. Female Yucatan miniature swine were treated with N-nitro-l-arginine methyl ester (l-NAME) to test the effect of chronic nitric oxide synthase (NOS) inhibition on the ACTH response to exercise. In addition, we tested the effect of NOS inhibition on blood flow to tissues of the HPA axis and report the effects of handling and treadmill exercise on the plasma concentrations of ACTH and cortisol. Chronic NOS inhibition decreased plasma NOx levels by 44%, increased mean arterial blood pressure by 46%, and increased expression of neuronal NOS in carotid arteries. Vascular conductance was decreased in the frontal cortex, the hypothalamus, and the adrenal gland. Chronic NOS inhibition exaggerated the ACTH response to exercise. In contrast, chronic NOS inhibition decreased the ACTH response to restraint, suggesting that the role of NO in modulating HPA activity is stressor dependent. These results demonstrate that NOS activity modulates the response of the neuroendocrine component of the HPA axis during exercise stress.

scholarly journals Systemic hypotensive effects of testosterone are androgen structure-specific and neuronal nitric oxide synthase-dependent

2015 ◽  
Vol 309 (2) ◽  
pp. R189-R195 ◽  
Author(s):  
Mercedes Perusquía ◽  
Clayton D. Greenway ◽  
Lisa M. Perkins ◽  
John N. Stallone
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Neuronal Nitric Oxide Synthase ◽  
Sprague Dawley ◽  
Peripheral Vasculature ◽  
Similar Reduction ◽  
Arterial Blood ◽  
Sd Rats ◽  
Oxide Synthase

Testosterone (TES) and other androgens exert a direct vasorelaxing action on the vasculature in vitro that is structurally specific and independent of cytosolic androgen receptor (AR). The effects of intravenous androgen infusions on mean arterial blood pressure (BP) and heart rate (HR) were determined in conscious, unrestrained, chronically catheterized, ganglionically blocked (hexamethonium, HEX; 30 mg/kg ip) male Sprague-Dawley (SD) and testicular-feminized male (Tfm; AR-deficient) rats, 16–20 wk of age. BP and HR were recorded at baseline and with increasing doses of androgens (0.375–6.00 μmol·kg−1·min−1 iv; 10 min/dose). Data are expressed as means ± SE ( n = 5–8 rats/group). In SD rats, baseline BP and HR averaged 103 ± 4 mmHg and 353 ± 12 beats/min (bpm). TES produced a dose-dependent reduction in BP to a low of 87 ± 4 mmHg (Δ16%), while HR was unchanged (354 ± 14 bpm). Neither BP (109 ± 3 mmHg) nor HR (395 ± 13 bpm) were altered by vehicle (10% EtOH in 0.9% saline; 0.15 ml·kg−1·min−1, iv). In Tfm, TES produced a similar reduction in BP (99 ± 3 to 86 ± 3 mmHg, Δ13%); HR was unchanged (369 ± 18 bpm). In SD, 5β-dihydrotestosterone (genomically inactive metabolite) produced a greater reduction in BP than TES (102 ± 2 to 79 ± 2 mmHg, Δ23%); HR was unchanged (361 ± 9). A 20-μg iv bolus of sodium nitroprusside in both SD and Tfm rats reduced BP 30–40 mmHg, while HR was unchanged, confirming blockade by HEX. Pretreatment of SD rats with neuronal nitric oxide synthase (nNOS) inhibitor (S-methyl-thiocitrulline, SMTC; 20 μg·kg−1·min−1 × 30 min) abolished the hypotensive effects of TES infusion on BP (104 ± 2 vs. 101 ± 2 mmHg) and HR (326 ± 11 vs. 324 ± 8 bpm). These data suggest the systemic hypotensive effect of TES and other androgens involves a direct vasodilatory action on the peripheral vasculature which, like the effect observed in isolated arteries, is structurally specific and AR-independent, and involves activation of nNOS.

scholarly journals Regulation of nitric oxide synthase isoforms and role of nitric oxide during prostaglandin F2alpha-induced luteolysis in rabbits

Reproduction ◽  
2003 ◽  
pp. 807-816 ◽  
Author(s):  
C Boiti ◽  
G Guelfi ◽  
D Zampini ◽  
G Brecchia ◽  
A Gobbetti ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Time Course ◽  
Plasma Concentrations ◽  
Physiological Role ◽  
Total Activity ◽  
Corpora Lutea ◽  
Prostaglandin F ◽  
Oxide Synthase

Total activity of nitric oxide synthase (NOS) and the gene expression of both endothelial NOS (eNOS) and inducible NOS (iNOS) isoforms in corpora lutea of pseudopregnant rabbits were examined during prostaglandin F(2alpha) (PGF(2alpha))-induced luteolysis. Corpora lutea were collected at 0, 6, 12, 24 and 48 h after an injection of PGF(2alpha) at day 9 of pseudopregnancy. At 12 h after PGF(2alpha) administration, luteal mRNA encoding eNOS decreased (P0.05) by 40% and remained low throughout the subsequent 36 h, whereas eNOS protein increased (P0.05) two- to threefold. By contrast, expression of mRNA encoding iNOS was poor and remained fairly constant, but transcription increased eightfold (P0.01) within 6 h after PGF(2alpha) treatment and then decreased to values similar to those of controls. Total NOS activity increased twofold (P0.01) at 6 h after treatment and remained high thereafter, whereas progesterone concentrations in explanted corpora lutea decreased (P0.01) from 302.4+/-42.3 pg x mg(-1) at day 9 to 58.6+/-8.3 at 48 h later, and peripheral plasma concentrations of progesterone declined too. Long-term administration of Nomega-nitro-L-arginine methyl ester (0.6 g l(-1) per os) from day 2 of pseudopregnancy onward partially blocked the luteolytic action of PGF(2alpha) administered at day 9 of pseudopregnancy. In nitric oxide (NO)-deficient rabbits, progesterone concentrations remained higher (P0.01) than in controls at 24-48 h after PGF(2alpha) administration (4.5 to 3.2 ng x ml(-1), respectively). These data are the first to characterize NOS activity. The time course of expression of eNOS and iNOS in rabbit corpora lutea during PGF(2alpha)-induced luteolysis gives additional support to a physiological role of NO in the regulation of regression of corpora lutea in rabbits.

Plasma arginine metabolites reflect airway dysfunction in a murine model of allergic airway inflammation

2015 ◽  
Vol 118 (10) ◽  
pp. 1229-1233 ◽  
Author(s):  
Jeremy A. Scott ◽  
Michelle L. North ◽  
Mahrouk Rafii ◽  
Hailu Huang ◽  
Paul Pencharz ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Airway Inflammation ◽  
Plasma Concentrations ◽  
Allergic Airway Inflammation ◽  
Airway Responsiveness ◽  
Arginase Activity ◽  
Therapeutic Interventions ◽  
Oxide Synthase

l-Arginine metabolism is important in the maintenance of airway tone. Shift of metabolism from the nitric oxide synthase to arginase pathways contributes to the increased airway responsiveness in asthma. We tested the hypothesis that systemic levels of l-arginine metabolites are biomarkers reflective of airway dysfunction. We used a mouse model of acute allergic airway inflammation to OVA that manifests with significant airway hyperresponsiveness to methacholine. To determine tissue arginase activity in vivo, the isotopic enrichment of an infused l-arginine stable isotope and its product amino acid l-ornithine were measured in lung and airway homogenates using liquid chromatography-tandem mass spectrometry. Tissue and plasma concentrations of other l-arginine metabolites, including l-citrulline and symmetric and asymmetric dimethylarginine, were measured and correlated with lung arginase activity and methacholine responsiveness of the airways. The effectiveness of intratracheal instillation of an arginase inhibitor (boronoethylcysteine) on pulmonary arginase activity and circulating concentrations of l-arginine metabolites was also studied. We demonstrate that 1) plasma indexes of l-arginine bioavailability and impairment of nitric oxide synthase function correlate with airway responsiveness to methacholine; 2) plasma levels of l-ornithine predict in vivo pulmonary arginase activity and airway function; and 3) acute arginase inhibition reduces in vivo pulmonary arginase activity to control levels and normalizes plasma l-ornithine, but not l-arginine, bioavailability in this model. We conclude that plasma l-ornithine may be useful as a systemic biomarker to predict responses to therapeutic interventions targeting airway arginase in asthma.

scholarly journals Endothelial nitric oxide synthase levels and their response to exercise in patients with slow coronary flow

2013 ◽  
Vol 24 (9) ◽  
pp. 355-359 ◽  
Author(s):  
Hakan Tasolar ◽  
Ferhat Eyyupkoca ◽  
Erdal Akturk ◽  
Yasin Karakus ◽  
Mehmet Cansel ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Endothelial Nitric Oxide Synthase ◽  
Coronary Flow ◽  
Slow Coronary Flow ◽  
Oxide Synthase ◽  
Response To Exercise ◽  
Endothelial Nitric Oxide

Nitric oxide does not mediate autoregulation of retinal blood flow in newborn pig

1995 ◽  
Vol 269 (3) ◽  
pp. H1065-H1072 ◽  
Author(s):  
J. M. Gidday ◽  
Y. Zhu
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Retinal Blood Flow ◽  
Nitric Oxide Synthase Inhibitor ◽  
Arterial Blood ◽  
Synthase Inhibitor ◽  
Oxide Synthase ◽  
Arteriolar Diameter ◽  
Retinal Arteriolar ◽  
Retinal Arteriolar Diameter

Isoflurane-anesthetized newborn pigs were used to test the hypothesis that nitric oxide mediates autoregulatory dilations of retinal arterioles. Fundus images were monitored by videomicroscopy at x310, and stimulus-induced changes in retinal arteriolar diameter were measured by on-line image analysis. Dilatative responses to systemic hypoxia (arterial O2 tension 20-30 mmHg), hypotension (mean arterial blood pressure 40 mmHg), or hypercapnia (arterial CO2 tension 70-85 mmHg) were assessed after intravitreal microsuffusion of the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) over the observed arterioles. Twenty-five nanomoles L-NMMA constricted arterioles by 24 +/- 2% (P < 0.01; n = 17 pigs); a significant constriction (14 +/- 2%) was still observed 80 min after drug administration (n = 5). Complete nitric oxide synthase inhibition at this dose was indicated by the findings that co-administration of 2.5 mumol L-arginine reversed this constriction within 17 +/- 2 min (n = 3), that L-NMMA, but not D-NMMA, completely inhibited the 20 +/- 3% P < 0.01) arteriolar dilation induced by intravitreal acetylcholine (7.5 nmol; n = 4), and that no additional constriction was evidenced after administration of a 10-fold greater concentration of L-NMMA (n = 8). However, despite the prominent arteriolar constriction induced by L-NMMA under baseline conditions, increases in retinal arteriolar diameter still occurred in response to hypoxia (n = 5), hypotension (n = 4), or hypercapnia (n = 5) in animals pretreated with 50 nmol L-NMMA; these responses did not differ significantly from arteriolar dilations observed in untreated control animals (n = 16) subjected to the same stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)

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