scholarly journals Acute Effects of Triiodothyronine on Endothelial Function in Human Subjects

2007 ◽  
Vol 92 (1) ◽  
pp. 250-254 ◽  
Author(s):  
Raffaele Napoli ◽  
Vincenzo Guardasole ◽  
Valentina Angelini ◽  
Emanuela Zarra ◽  
Daniela Terracciano ◽  
...  
Keyword(s):  
Endothelial Function ◽  
Dose Response ◽  
Vascular Reactivity ◽  
Controlled Trial ◽  
University Hospital ◽  
Acute Effects ◽  
Response Curves ◽  
Double Blind ◽  
Low T3 ◽  
Dose Response Curves

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.

scholarly journals Modification of vasodilator response in streptozotocin-induced diabetic rat

1999 ◽  
Vol 77 (12) ◽  
pp. 980-985 ◽  
Author(s):  
Jean-François Bouchard ◽  
Éric C Dumont ◽  
Daniel Lamontagne
Keyword(s):  
Diabetes Mellitus ◽  
Adenylyl Cyclase ◽  
Dose Response ◽  
Vascular Reactivity ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Response Curves ◽  
Experimental Conditions ◽  
Isolated Hearts ◽  
Dose Response Curves

Functional dilatory response in streptozotocin-induced diabetic rats was investigated using thoracic aortas, isolated hearts, and mesenteric beds. Dose-response curves to the PGI2 analogue iloprost on phenylephrine-preconstricted rings of diabetic rats and controls were comparable. In contrast, decreased vasodilation in diabetic rats was observed when dose-response curves to iloprost were performed in hearts and on phenylephrine-preconstricted mesenteric beds. Dose-response curves to forskolin, an adenylyl cyclase activator, performed with hearts and phenylephrine-preconstricted aortic rings and isolated mesenteric beds of diabetic rats and controls were comparable. However, a decreased vasodilation to the ATP-sensitive potassium channel (KATP) activator lemakalim was observed in diabetic hearts, but not in aortic rings and mesenteric beds. In conclusion, under our experimental conditions, diabetes mellitus affects the vasodilation to iloprost in both coronary and mesenteric beds, but not in the aorta. In the heart, this modification of vascular reactivity may be due to a decrease in KATP channel mediated response and not to a decreased activity of adenylyl cyclase. At this time, in the isolated mesenteric bed, the mechanism of this modification in vascular reactivity remains unknown.Key words: diabetes mellitus, iloprost, KATP channels, adenylyl cyclase, aorta, coronary circulation, mesenteric bed.

scholarly journals Nifedipine-sensitive vascular reactivity of femoral arteries in WKY: the effect of pertussis toxin pretreatment and endothelium removal

2007 ◽  
pp. 663-666
Author(s):  
S Líšková ◽  
J Kuneš ◽  
J Zicha
Keyword(s):  
G Proteins ◽  
Pertussis Toxin ◽  
Dose Response ◽  
Vascular Reactivity ◽  
Response Curves ◽  
Femoral Arteries ◽  
Voltage Dependent ◽  
Dose Response Curves ◽  
Vasodilator Action ◽  
The Right

Maintenance of norepinephrine (NE)-induced contraction is dependent on Ca(2+) influx through L-type voltage-dependent Ca(2+) channels (VDCC), which is opposed by nitric oxide. Adrenergic receptors are coupled with different G proteins, including inhibitory G proteins (Gi) that can be inactivated by pertussis toxin (PTX). Our study was aimed to investigate the effects of endothelium removal, PTX pretreatment and acute VDCC blockade by nifedipine on the contractions of femoral arteries stimulated by norepinephrine. We used 12-week-old male WKY, half of the rats being injected with PTX (10 microg/kg i.v., 48 h before the experiment), which considerably reduced their blood pressure (BP). Contractions of isolated arteries were measured using Mulvany-Halpern myograph. NE dose-response curves determined in femoral arteries from PTX-treated WKY rats were shifted to the right compared to those from control WKY. On the contrary, removal of endothelium augmented NE dose-response curves shifting them to the left. Acute VDCC blockade by nifedipine (10(-7) M) abolished all differences in NE dose-response curves which were dependent on the presence of either intact endothelium or functional Gi proteins because all NE dose-response curves were identical to the curve seen in vessels with intact endothelium from PTX-treated animals. We can conclude that BP reduction after PTX injection is accompanied by the attenuation of NE-induced contraction of femoral arteries irrespective of endothelium presence. Moreover, our data indicate that both vasodilator action of endothelium and Gi-dependent vasoconstrictor effect of norepinephrine operate via the control of Ca(2+) influx through VDCC.

Pulmonary vascular reactivity after repetitive exposure to selected biogenic amines

1983 ◽  
Vol 55 (6) ◽  
pp. 1868-1876 ◽  
Author(s):  
M. Cutaia ◽  
R. J. Porcelli
Keyword(s):  
Biogenic Amines ◽  
Dose Response ◽  
Vascular Reactivity ◽  
Lower Lobe ◽  
Left Lower Lobe ◽  
Base Line ◽  
Response Curves ◽  
Arterial Blood ◽  
Repetitive Exposure ◽  
Dose Response Curves

The present study investigated the effects of repetitive exposure to a select group of biogenic amines (epinephrine, norepinephrine, histamine, and serotonin) on pulmonary vascular reactivity by constructing and analyzing a set of four sequential cumulative dose-response curves to one biogenic amine in the isolated blood-perfused left lower lobe of the cat lung in vivo. The dose-response curves were obtained under conditions of constant flow, insuring that the observed pressure changes in the lobe were pressor responses resulting from vasoconstriction rather than flow-related changes. Histamine and epinephrine demonstrated a progressive loss of initial vasoconstrictor activity, whereas the responses to serotonin remained unchanged after repetitive exposure. Norepinephrine demonstrated two different patterns of response, depending on the dose range employed; norepinephrine (0.068-2.27 nmol/ml) demonstrated a loss of the original vasoconstrictor activity, in a pattern similar to histamine and epinephrine, while higher doses of norepinephrine (0.34-9.1 nmol/ml) demonstrated no change in activity with a left shift in the concentration at which the maximal responses occurred, suggesting an increase in sensitivity as a result of repeated exposure. These results were obtained in the absence of significant alterations of arterial blood gases, changes in base-line tone in the experimental left lower lobe, or the development of severe pulmonary edema. These data suggest that only the agents that are capable of stimulating antagonistic vasoconstrictor and vasodilator receptors demonstrated a loss of pulmonary vasoconstrictor activity, which may result from a functional shift in the balance of antagonistic receptor activity with continued exposure.

The Effects of Melatonin Premedication on Propofol and Thiopental Induction Dose???Response Curves: A Prospective, Randomized, Double-Blind Study

2006 ◽  
Vol 103 (6) ◽  
pp. 1448-1452 ◽  
Author(s):  
Mohamed Naguib ◽  
Abdulhamid H. Samarkandi ◽  
Mohamed A. Moniem ◽  
Emad El-Din Mansour ◽  
Ahmad A. Alshaer ◽  
...  
Keyword(s):  
Dose Response ◽  
Blind Study ◽  
Double Blind Study ◽  
Response Curves ◽  
Double Blind ◽  
Induction Dose ◽  
Dose Response Curves

Variability of airway responses to inhaled histamine in normal subjects

1979 ◽  
Vol 47 (1) ◽  
pp. 51-58 ◽  
Author(s):  
M. P. Habib ◽  
P. D. Pare ◽  
L. A. Engel
Keyword(s):  
Dose Response ◽  
Lung Volume ◽  
Normal Population ◽  
Normal Subjects ◽  
Beta Blockade ◽  
Forced Expiration ◽  
Response Curves ◽  
Double Blind ◽  
Dose Response Curves ◽  
Airway Responses

Dose-response curves to inhaled histamine were studied in 12 normal subjects. Pulmonary resistance (RL) and dynamic compliance (Cdyn) were measured during tidal breathing, and maximum expiratory flow rates, at an absolute lung volume corresponding to 40% of control vital capacity, were obtained during forced expiration from tidal end inspiration (Vmax40p) and from total lung capacity (Vmax40c). Threshold was defined as the histamine dose at which a departure from the range of normal measurements was observed. RL and Vmax40p indicated lowest threshold values, which varied by a factor of 32 and 38, respectively. There was no correlation between reactivity, which reflects the slope of the dose-response curve beyond the threshold dose, and threshold doses, nor between the initial RL (normalized for lung volume) and either threshold or reactivity. In eight subjects, restudied on two occasions after 10 mg propranolol or after saline, injected in a double-blind manner, there was no change in the dose-response curves. These results indicate that different indices of bronchoconstriction may yield different dose-response curves and hence different sensitivities. In addition, a wide variation of airway responses to inhaled histamine exists in the normal population and beta-blockade does not influence this variability.

Vascular Reactivity in the Pathogenesis of Spontaneous Hypertension

1979 ◽  
Vol 57 (s5) ◽  
pp. 51s-53s ◽  
Author(s):  
Kathleen H. Berecek ◽  
W. Rascher ◽  
F. Gross
Keyword(s):  
Dose Response ◽  
Vascular Reactivity ◽  
Response Curves ◽  
Enhanced Resistance ◽  
Vascular Beds ◽  
Dose Response Curves ◽  
Wistar Kyoto ◽  
6 Hydroxydopamine ◽  
Renal Vascular ◽  
Neonatal Sympathectomy

1. Alterations in vascular reactivity were assessed in isolated artificially perfused kidneys from stroke-prone spontaneously hypertensive (spSH) rats at different stages of hypertension and after neonatal sympathectomy with 6-hydroxydopamine (6-OHDA). 2. During the pre-hypertensive stage, and the early and chronic stages of hypertension, the responses to noradrenaline, vasopressin, serotonin and angiotensin II were enhanced in renal vascular beds from spSH animals compared with age- and sex-matched Wistar—Kyoto (WK) rats; dose—response curves were shifted to the left, had steeper slopes, greater maximal responses and decreased thresholds. 3. With increasing severity and duration of hypertension, renal vascular resistance at maximal vasodilatation increased, the slopes of the dose-response curves were steeper and maximal responses were greater. 4. Neonatal sympathectomy with 6-OHDA greatly attenuated but did not prevent the eventual development of hypertension; furthermore, this treatment had no effect on the enhanced resistance or reactivity in renal vascular beds from spSH rats. 5. The appearance of enhanced resistance and reactivity in the early stages of hypertension and the inability to prevent these vascular changes by neonatal sympathectomy suggest that these alterations are a primary pathogenic mechanism in spSH rats.

Abstract 307: Enhancement of Cerebrovascular Relaxation by Angiotensin II Type 2 Receptor Agonist, C21, is Lost in Type 2 Diabetes

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Abdelrahman Y Fouda ◽  
Trevor Hardigan ◽  
Sahar Soliman ◽  
Bindu Pillai ◽  
Adviye Ergul ◽  
...  
Keyword(s):  
Endothelial Function ◽  
Dose Response ◽  
Diabetic Rats ◽  
Dependent Manner ◽  
Response Curves ◽  
Stroke Outcomes ◽  
Gk Rats ◽  
Basilar Arteries ◽  
Dose Response Curves

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.

Dose-response Curves in the Fibrin Plate Assay Fibrinolytic Activity of Proteases

1974 ◽  
Vol 32 (02/03) ◽  
pp. 356-365 ◽  
Author(s):  
F Haverkate ◽  
D. W Traas
Keyword(s):  
Dose Response ◽  
Fibrinolytic Activity ◽  
Enzyme Concentration ◽  
Response Curves ◽  
Agar Gel ◽  
Porcine Tissue ◽  
Plate Assay ◽  
Fibrin Plate ◽  
Different Types ◽  
Dose Response Curves

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.

BIOASSAY OF THYROID HORMONE USING HYPOTHYROID TADPOLES

1962 ◽  
Vol 41 (1) ◽  
pp. 143-153 ◽  
Author(s):  
U. Henriques
Keyword(s):  
Thyroid Hormone ◽  
Dose Response ◽  
Developmental Rate ◽  
Response Curves ◽  
Sodium Salts ◽  
Dose Response Curves

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.

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