The use of shear rate-diameter dose-response curves to assess endothelial function

2011 ◽  
Vol 14 (12) ◽  
pp. 339-344 ◽  
2007 ◽  
Vol 92 (1) ◽  
pp. 250-254 ◽  
Author(s):  
Raffaele Napoli ◽  
Vincenzo Guardasole ◽  
Valentina Angelini ◽  
Emanuela Zarra ◽  
Daniela Terracciano ◽  
...  

Abstract Context: Thyroid hormone regulates several cardiovascular functions, and low T3 levels are frequently associated with cardiovascular diseases. Whether T3 exerts any acute and direct effect on endothelial function in humans is unknown. Objective: Our objective was to clarify whether acute changes in serum T3 concentration affect endothelial function. Design, Setting, and Subjects: Ten healthy subjects (age, 24 ± 1 yr) participated in a double-blind, placebo-controlled trial at a university hospital. Interventions: T3 (or placebo) was infused for 7 h into the brachial artery to raise local T3 to levels observed in moderate hyperthyroidism. Vascular reactivity was tested by intraarterial infusion of vasoactive agents. Main Outcome Measures: We assessed changes in forearm blood flow (FBF) measured by plethysmography. Results: FBF response to the endothelium-dependent vasodilator acetylcholine was enhanced by T3 (P = 0.002 for the interaction between T3 and acetylcholine). The slopes of the dose-response curves were 0.41 ± 0.06 and 0.23 ± 0.04 ml/dl·min/μg in the T3 and placebo study, respectively (P = 0.03). T3 infusion had no effect on the FBF response to sodium nitroprusside. T3 potentiated the vasoconstrictor response to norepinephrine (P = 0.006 for the interaction). Also, the slopes of the dose-response curves were affected by T3 (1.95 ± 0.77 and 3.83 ± 0.35 ml/dl·min/mg in the placebo and T3 study, respectively; P < 0.05). The increase in basal FBF induced by T3 was inhibited by NG-monomethyl-l-arginine. Conclusions: T3 exerts direct and acute effects on the resistance vessels by enhancing endothelial function and norepinephrine-induced vasoconstriction. The data may help clarify the vascular impact of the low T3 syndrome and point to potential therapeutic strategies.


Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Abdelrahman Y Fouda ◽  
Trevor Hardigan ◽  
Sahar Soliman ◽  
Bindu Pillai ◽  
Adviye Ergul ◽  
...  

Background: Angiotensin type 1 receptor (AT1R) blockers provide vascular protection and improve stroke outcomes in young otherwise healthy animals. These effects are believed to be mediated by the indirect stimulation of AT2R signaling. The AT2R agonist, compound 21 (C21), improves endothelial function in peripheral vascular beds but its effect on cerebral endothelial function remains unknown. It is important to determine the vascular effects of C21 in diabetes, a comorbid condition which is known to worsen stroke outcomes. Methods: Endothelium-dependent relaxation was assessed in male Wistar and Type 2 diabetic Goto-Kakizaki (GK) rats (n=3-6) by measuring acetylcholine (ACh, 1 nM - 5 μm) induced dilatory response in basilar arteries. In a subset of experiments C21 dose response curves were generated (0.1 nM - 1 μM) or vessels were pre-incubated with 100 nM C21 ± 1 μM PD123319 (AT2R blocker) for 30 min prior to Ach dose response curves. Area under the curve (AUC) and half maximal effective concentration (EC50 nM) were calculated as indices of total relaxation and receptor sensitivity, respectively. Angiotensin receptors expression was measured by immunoblotting of brain homogenates. Results: AT2R agonist C21 dose response curves showed no basilar reactivity in either control or diabetic animals. Pre-incubation with C21 enhanced relaxation to Ach in control animals (vehicle 146.7 ± 3.9 vs C21 pretreatment 229.6 ± 11.6), which was abolished by the blockade of AT2R (176.9 ± 25.5, p=0.007). Similarly, C21 improved sensitivity in control animals (vehicle 110.5 ± 32 vs C21 pretreatment 11.9 ± 2) which was abolished in the presence of PD123319 (93.8 ± 31, p=0.04). Basilar artery relaxation (AUC) was impaired in diabetic GK rats (93.9 ± 1.8%) as compared to controls (146.7 ± 3.9%) and C21 had no effect (98 ± 8.9%) indicating a disease and treatment interaction (p<0.001). Normalized AT1R expression levels were 1 ± 0.04 and 0.98 ± 0.05 in control vs diabetic rats and respective AT2R levels were 1 ± 0.1 and 0.84 ± 0.09. Conclusion: C21 improves vascular relaxation in control but not in diabetic rats in an AT2R-dependent manner. Underlying mechanisms blunting response to C21 need to be further investigated and may impact the subsequent development of C21 as a treatment for stroke.


1974 ◽  
Vol 32 (02/03) ◽  
pp. 356-365 ◽  
Author(s):  
F Haverkate ◽  
D. W Traas

SummaryIn the fibrin plate assay different types of relationships between the dose of applied proteolytic enzyme and the response have been previously reported. This study was undertaken to determine whether a generally valid relationship might exist.Trypsin, chymotrypsin, papain, the plasminogen activator urokinase and all of the microbial proteases investigated, including brinase gave a linear relationship between the logarithm of the enzyme concentration and the diameter of the circular lysed zone. A similar linearity of dose-response curves has frequently been found by investigators who used enzyme plate assays with substrates different from fibrin incorporated in an agar gel. Consequently, it seems that this linearity of dose-response curves is generally valid for the fibrin plate assay as well as for other enzyme plate bioassays.Both human plasmin and porcine tissue activator of plasminogen showed deviations from linearity of semi-logarithmic dose-response curves in the fibrin plate assay.


1962 ◽  
Vol 41 (1) ◽  
pp. 143-153 ◽  
Author(s):  
U. Henriques

ABSTRACT A bioassay of thyroid hormone has been developed using Xenopus larvae made hypothyroid by the administration of thiourea. Only tadpoles of uniform developmental rate were used. Thiourea was given just before the metamorphotic climax in concentrations that produced neoteni in an early metamorphotic stage. During maintained thiourea neotoni, 1-thyroxine and 1-triiodothyronine were added as sodium salts to the water for three days and at the end of one week the stage of metamorphosis produced was determined. In this way identical dose-response curves were obtained for the two compounds. No qualitative differences between their effects were noted except that triiodothyronine seemed more toxic than thyroxine in equivalent doses. Triiodothyronine was found to be 7–12 times as active as thyroxine.


2005 ◽  
Vol 8 (4) ◽  
pp. E269-E274 ◽  
Author(s):  
Sydney L. Gaynor ◽  
Gregory D. Byrd ◽  
Michael D. Diodato ◽  
Yosuke Ishii ◽  
Anson M. Lee ◽  
...  

2001 ◽  
Author(s):  
Quinton J. Nottingham ◽  
Jeffrey B. Birch ◽  
Barry A. Bodt

2021 ◽  
Vol 3 (1) ◽  
pp. 181-188
Author(s):  
Peter Bracke ◽  
Eowyn Van de Putte ◽  
Wouter R. Ryckaert

Dose-response curves for circadian phase shift and melatonin suppression in relation to white or monochromatic nighttime illumination can be scaled to melanopic weighed illumination for normally constricted pupils, which makes them easier to interpret and compare. This is helpful for a practical applications.


2021 ◽  
Vol 21 (1) ◽  
pp. 69-110 ◽  
Author(s):  
Brian G. Vegetabile ◽  
Beth Ann Griffin ◽  
Donna L. Coffman ◽  
Matthew Cefalu ◽  
Michael W. Robbins ◽  
...  

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