Postischemic vasodilation in human forearm is dependent on endothelium-derived nitric oxide

1996 ◽  
Vol 270 (4) ◽  
pp. H1435-H1440 ◽  
Author(s):  
I. T. Meredith ◽  
K. E. Currie ◽  
T. J. Anderson ◽  
M. A. Roddy ◽  
P. Ganz ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Dose Response ◽  
Supply And Demand ◽  
Reactive Hyperemia ◽  
Normal Subjects ◽  
Response Relationship ◽  
Dose Response Relationship ◽  
Time Curve ◽  
Nitric Oxide Synthase Inhibitor ◽  
Hyperemic Flow

Although endothelium-derived nitric oxide contributes to basal vascular tone, little is known about its role in regulating blood flow during changes in metabolic supply and demand. We examined the contribution of endothelium-derived nitric oxide to reactive hyperemia in the forearm of 20 normal subjects (12 women, 8 men) aged 27 +/- 4 yr (means +/- SD), using the nitric oxide synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA). Forearm ischemia was induced by suprasystolic blood pressure cuff inflation for 5 min, and the subsequent hyperemic flow was recorded for 5 min using venous occlusion strain-gauge plethysmography. The efficacy of nitric oxide blockade was tested by comparing the dose-response relationship to the endothelium-dependent agonist, acetylcholine (3, 10, and 30 mg/min), before and after intra-arterial infusion of up to 2,000 mg/min of L-NMMA. L-NMMA produced a significant downward and rightward shift in the dose-response relationship to acetylcholine and a 39% reduction in response to the maximum dose (P < 0.001). In the presence of L-NMMA, peak hyperemic flow was reduced 16% (26.5 +/- 2.1 to 22.3 +/- 1.5 ml.min-1.100 ml of forearm-1, P < 0.03), and the minimum forearm vascular resistance was increased 22.8% (3.5 +/- 0.3 to 4.3 +/- 0.4 mmHg.ml-1.min.100 ml, P < 0.02). Total hyperemia, calculated from the area under the flow vs. time curve, at 1 and 5 min after cuff release was 17 and 23% less, respectively (13.6 +/- 1.2 vs. 11.3 +/- 1.1 and 31.8 +/- 2.7 vs. 24.6 +/- 1.8 ml/100 ml, P < 0.002), following L-NMMA. These data suggest that endothelium-derived nitric oxide plays a role in both reactive hyperemia and in the maintenance of the hyperemic response following ischemia in the forearm.

Dose-Response Relationship and Reproducibility of the Fall in Exhaled Nitric Oxide After Inhaled Beclomethasone Dipropionate Therapy in Asthma Patients

CHEST Journal ◽  
2001 ◽  
Vol 119 (5) ◽  
pp. 1322-1328 ◽  
Author(s):  
Philip E. Silkoff ◽  
Patricia McClean ◽  
Michael Spino ◽  
Lu Ann Erlich ◽  
Arthur S. Slutsky ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Dose Response ◽  
Beclomethasone Dipropionate ◽  
Exhaled Nitric Oxide ◽  
Response Relationship ◽  
Dose Response Relationship ◽  
Asthma Patients

Dose-Response Relationship to Inhaled Endotoxin in Normal Subjects

1997 ◽  
Vol 156 (4) ◽  
pp. 1157-1164 ◽  
Author(s):  
OLIVIER MICHEL ◽  
ANNE-MARIE NAGY ◽  
MARC SCHROEVEN ◽  
JEAN DUCHATEAU ◽  
JEAN NÈVE ◽  
...  
Keyword(s):  
Dose Response ◽  
Normal Subjects ◽  
Response Relationship ◽  
Dose Response Relationship

scholarly journals Stimulatory Effect of Adrenocorticotropin on Cortisol, Aldosterone, and Dehydroepiandrosterone Secretion in Normal Humans: Dose-Response Study*

2000 ◽  
Vol 85 (9) ◽  
pp. 3141-3146 ◽  
Author(s):  
Emanuela Arvat ◽  
Lidia Di Vito ◽  
Fabio Lanfranco ◽  
Mauro Maccario ◽  
Claudia Baffoni ◽  
...  
Keyword(s):  
Dose Response ◽  
Normal Subjects ◽  
Response Relationship ◽  
Dose Response Relationship ◽  
Clear Dose Response ◽  
Normal Humans ◽  
Effective Doses ◽  
Releasing Effect ◽  
Dose Response Effect ◽  
Dose Response Study

Abstract The short ACTH test is widely used in clinical practice for the diagnosis of adrenal insufficiency. It is classically performed administering 250.0 μg ACTH(1–24) although 1.0 μg ACTH dose has been reported having maximal stimulatory effect on cortisol levels in normal subjects. We aimed to define the maximal and the minimal stimulatory ACTH dose on cortisol, aldosterone, and dehydroepiandrosterone (DHEA) in humans. To this goal, in 12 normal volunteers (6 males and 6 females; age, 22–34 yr; body mass index 20–25 kg/m2; body surface 1.6–1.9 m2), we studied the dose-response effect of eight ACTH doses (0.01, 0.03, 0.06, 0.125, 0.5, 1.0, 25.0, and 250.0 μg) on cortisol, aldosterone, and DHEA levels. Each ACTH dose administered at 0 min was followed by a second ACTH dose of 250.0 μg at +60 min. The cortisol Δ areas under response curve (ΔAUCs) after all ACTH doses, apart from 0.01 μg, were significantly higher (P &lt; 0.02) than that after placebo, showing a clear dose-response relationship (P&lt; 0.001). The doses of 0.03 and 1.0 μg ACTH were the minimal and maximal effective doses, respectively. The cortisol response to 250.0μ g ACTH was not modified by pretreatment with 0.01, 0.03, and 0.06μ g ACTH doses, whereas it was progressively reduced by increasing the dose of ACTH pretreatment (P &lt; 0.001). The aldosteroneΔ AUCs to all but 0.01 μg ACTH doses were significantly higher (P &lt; 0.02) than that after placebo, showing a clear dose-response relationship (P &lt; 0.001). The dose of 0.03 μg was the minimal effective stimulating dose, whereas 25.0 μg showed the same aldosterone-releasing effect of 250.0 μg. The aldosterone response to 250.0 μg ACTH, preceeded by placebo, was not modified by pretreatment with 0.01 and 0.03 μg ACTH doses, whereas it was reduced by increasing the dose of ACTH pretreatment (P &lt; 0.05–0.02). The DHEA ΔAUCs to all ACTH doses were significantly higher (P &lt; 0.01) than that after placebo, showing a clear dose-response relationship (P&lt; 0.001). The doses of 0.01 and 1.0 μg ACTH were the minimal and maximal effective dose, respectively. The DHEA response to 250.0 μg ACTH was not modified by pretreatment with 0.01, 0.03, 0.06, and 0.125μ g ACTH doses, whereas it was progressively reduced by pretreatment with 0.5, 1.0, and 25.0 μg ACTH doses (P &lt; 0.01). In conclusion, these results show that an extremely low ACTH dose is needed to stimulate adrenal steroids and, among them, DHEA seems the most sensitive to corticotropin stimulation.

scholarly journals Urinary Excretion of Erythropoietin in Normal Men and Women

Blood ◽  
1966 ◽  
Vol 28 (3) ◽  
pp. 344-353 ◽  
Author(s):  
RAYMOND ALEXANIAN ◽  
Brenda Prewitt
Keyword(s):  
Urinary Excretion ◽  
Dose Response ◽  
Normal Subjects ◽  
Adult Males ◽  
Response Relationship ◽  
Dose Response Relationship ◽  
Men And Women ◽  
Linear Dose ◽  
Prepubertal Boys ◽  
Normal Men

Abstract The bioassay of erythropoietin in polycythemic mice was modified to include a protein-depletion diet and a divided erythropoietin injection schedule. Although less than 0.05 unit of standard erythropoietin was not detected, a more linear dose/response relationship resulted from increasing doses of erythropoietin in the 0.1 to 1.0 unit range. The amount of erythropoietin in concentrated specimens prepared from the 24-hour urinary excretion of 25 normal subjects was measured in comparison with known quantities of standard erythropoietin. A mean daily erythropoietin excretion in men of 2.8 ± 1.3 units, in women of 0.9 ± 0.4 unit and in prepubertal boys of 1.0 unit was calculated. The higher erythropoietin excretion in adult males may be secondary to a greater production of erythropoietin in this sex.

A SUBCUTANEOUS INJECTION ASSAY FOR ANTI-ANDROGENS IN THE CHICK

1962 ◽  
Vol 41 (2) ◽  
pp. 268-273 ◽  
Author(s):  
Ralph I. Dorfman
Keyword(s):  
Dose Response ◽  
Subcutaneous Injection ◽  
Response Relationship ◽  
Dose Response Relationship

ABSTRACT The stimulating action of testosterone on the chick's comb can be inhibited by the subcutaneous injection of 0.1 mg of norethisterone or Ro 2-7239 (2-acetyl-7-oxo-1,2,3,4,4a,4b,5,6,7,9,10,10a-dodecahydrophenanthrene), 0.5 mg of cortisol or progesterone, and by 4.5 mg of Mer-25 (1-(p-2-diethylaminoethoxyphenyl)-1-phenyl-2-p-methoxyphenyl ethanol). No dose response relationship could be established. Norethisterone was the most active anti-androgen by this test.

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