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.

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.

Histamine dose-response curves in guinea pigs

1985 ◽  
Vol 58 (2) ◽  
pp. 625-634 ◽  
Author(s):  
W. C. Hulbert ◽  
T. McLean ◽  
B. Wiggs ◽  
P. D. Pare ◽  
J. C. Hogg
Keyword(s):  
Dose Response ◽  
Guinea Pigs ◽  
Response Curve ◽  
Dynamic Compliance ◽  
Dose Response Curve ◽  
Base Line ◽  
Response Curves ◽  
Mechanically Ventilated ◽  
Dose Response Curves ◽  
The Right

Histamine dose-response curves were performed on anesthetized tracheostomized guinea pigs that were paralyzed and mechanically ventilated at a constant tidal volume and breathing frequency. The dose was calculated by generating an aerosol of known concentration and measuring the volume delivered to the lung. Increasing the dose was accomplished by increasing the number of breaths of aerosol delivered. The response to each dose was determined by measuring the change in airway resistance (RL) and dynamic compliance (Cdyn) using the method of Von Neergaard and Wirz (Z. Klin. Med. 105: 51–82, 1927). With increasing doses of histamine, RL increased and reached a plateau at approximately five times the base-line value and Cdyn fell to approximately 20% of its initial value. The variability in the base-line and maximum response as well as the calculated sensitivity and reactivity was less than that previously reported. Propranolol pretreatment increased resting RL and shifted the dose-response curve for RL to the left of the controls, increasing reactivity but not sensitivity. Atropine shifted the dose-response curve to the right of the control, decreasing sensitivity but without changing reactivity. The data for Cdyn showed that atropine pretreatment caused a higher resting value and propranolol pretreatment a lower value at the highest histamine dose but no differences in either sensitivity or reactivity.

Temporal and regional variability of collateral resistance response to histamine

1988 ◽  
Vol 64 (5) ◽  
pp. 2142-2149 ◽  
Author(s):  
M. S. Ludwig ◽  
S. A. Shore ◽  
K. Anderson ◽  
J. M. Drazen
Keyword(s):  
Dose Response ◽  
Coefficient Of Variation ◽  
Geometric Mean ◽  
Base Line ◽  
Response Curves ◽  
Regional Variability ◽  
Resistance Response ◽  
Dose Response Curves

Using the wedged bronchoscope technique, we measured the changes in collateral resistance (Rcoll) in dogs resulting from exposure to aerosols of increasing concentrations of histamine. Histamine dose-response curves were performed in each of two to three separate lobar segments of an individual mongrel dog's lungs. Five dogs were studied. The same segments were reexamined on later occasions (2–11 wk apart) to determine whether the responsiveness to histamine had altered with time. Measurements of base-line Rcoll for a given segment were reproducible (coefficient of variation 0.48). In contrast, we observed that the estimated dose of histamine required to increase Rcoll by 50% (ED150Rcoll) was extremely variable both among lung segments of an individual dog on a single experimental day (geometric mean variability of 40-fold) and for a given segment when reexamined on repeated occasions (geometric mean variability of 47-fold). The ED150Rcoll did not correlate with the base-line Rcoll. The degree of variability we observed suggests that peripheral contractile elements are under the influence of powerful local modulating factors that vary both regionally and temporally.

Tachyphylaxis to inhaled aerosolized histamine in anesthetized dogs

1985 ◽  
Vol 59 (5) ◽  
pp. 1355-1363 ◽  
Author(s):  
S. Shore ◽  
J. G. Martin
Keyword(s):  
Dose Response ◽  
Dynamic Compliance ◽  
Pulmonary Mechanics ◽  
Base Line ◽  
Response Curves ◽  
Low Concentrations ◽  
Anesthetized Dogs ◽  
Dose Response Curves ◽  
High Concentrations ◽  
Airway Responses

Three consecutive dose-response curves to inhaled aerosolized histamine, separated by 1-h intervals, were obtained in 20 anesthetized mongrel dogs. In general, successive histamine dose-response curves shifted progressively rightward. Changes in pulmonary resistance (RL) and dynamic compliance (Cdyn) in response to low concentrations of histamine were reproducible, but responses to high concentrations (sufficient to at least double RL or decrease Cdyn by at least 30%) decreased on successive dose-response curves. The concentration of histamine required to double RL increased significantly (P less than 0.05) from 1.01 mg/ml on the first to 1.62 and 2.02 mg/ml on the second and third dose-response curves. In contrast, consecutive methacholine dose-response curves were not significantly different. Indomethacin pretreatment (5 mg/kg iv) prevented histamine tachyphylaxis, whereas atropine (4 mg iv) did not. However, indomethacin did not alter base-line pulmonary mechanics or histamine responsiveness as measured on the first dose-response curve. We conclude that tachyphylaxis to inhaled aerosolized histamine occurs in anesthetized dogs. Our results are consistent with an important role for endogenous prostaglandins in modulating the airway responses to repeated histamine exposures.

Enhanced airway responses to substance P after repeated challenge in guinea pigs

1989 ◽  
Vol 66 (2) ◽  
pp. 955-961 ◽  
Author(s):  
S. A. Shore ◽  
J. M. Drazen
Keyword(s):  
Substance P ◽  
Dose Response ◽  
Guinea Pigs ◽  
Response Curve ◽  
Enzyme Inhibitor ◽  
Dose Response Curve ◽  
Base Line ◽  
Response Curves ◽  
Dose Response Curves ◽  
Airway Responses

We performed three consecutive dose-response curves to rapid intravenous infusions of substance P (SP) in anesthetized, mechanically ventilated guinea pigs. The dose of SP required to decrease pulmonary conductance to 50% of its base-line value (ED50GL) decreased 2.8-fold (P less than 0.002) and 3.3-fold (P less than 0.001) on the second and third dose-response curves, respectively, compared with the first. SP did not alter airway responses to intravenous histamine but did cause a significant (3.7-fold) decrease in ED50GL for dose-response curves to intravenous capsaicin, an agent that causes bronchoconstriction by release of endogenous tachykinins. The neutral metalloendopeptidase inhibitor thiorphan (0.5 mg) and the angiotensin-converting enzyme inhibitor captopril (1.7 mg) both caused a marked enhancement of airway responses to SP observed on the first dose-response curve but did not alter the enhancement of SP-induced airway responses produced by repeated SP challenge. The anticholinergic atropine (5 mg/kg iv), the antihistamine mepyramine (8 mg/kg iv), and the cyclooxygenase inhibitor indomethacin (30 mg/kg ip) had no effect on the first SP dose-response curve. Atropine and mepyramine did not prevent the enhancement of SP responses observed with repeated challenge, but after pretreatment with either indomethacin or acetylsalicylic acid, dose-response curves to SP were reproducible. Our results indicate that airway responses to intravenous SP are enhanced with repeated SP challenge and suggest that cyclooxygenase products of arachidonic acid metabolism are involved in the mediation of this phenomenon.

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.

Sensitivity of bronchoprovocation and tracheal mucous velocity in detecting airway responses to O3

1980 ◽  
Vol 48 (5) ◽  
pp. 789-793 ◽  
Author(s):  
W. M. Abraham ◽  
A. J. Januszkiewicz ◽  
M. Mingle ◽  
M. Welker ◽  
A. Wanner ◽  
...  
Keyword(s):  
Dose Response ◽  
Airway Hyperreactivity ◽  
Base Line ◽  
Response Curves ◽  
Pulmonary Flow ◽  
Short Term Exposure ◽  
Significant Depression ◽  
Dose Response Curves ◽  
Airway Responses ◽  
Conscious Sheep

This study was undertaken to determine whether measurements of tracheal mucous velocity or airway reactivity to inhaled carbachol more sensitively detect airway effects of inhaled ozone (O3) in conscious sheep. Dose-response curves of mean pulmonary flow resistance (RL) to carbachol were obtained by measuring RL after five breaths of carbachol aerosol with stepwise increases in drug concentration. The animals then breathed 0.5 ppm O3 through an endotracheal tube for 2 h. The dose-response curves were repeated immediately after the 0.5 ppm O3 exposure and 24 h later. In the eight sheep studied, there were no significant alterations in base-line RL immediately after or 24 h after 0.5 ppm O3. Airway hyperreactivity was not apparent immediately after the sheep breathed 0.5 ppm O3, but it was evident 24 h later. In contrast, six sheep that breathed 0.5 ppm O3 in the same manner for 2 h did not show a significant depression in tracheal mucous velocity the same day or 24 h later. Exposure to 1 ppm O3 for 2 h resulted in airway hyperreactivity immediately after the exposure and elevated base-line RL 24 h later; 2 ppm O3 produced an increase in base-line RL immediately after exposure. We conclude that, in conscious sheep, airway hyperreactivity appears to be a more sensitive indicator of airway effects produced by short-term exposure to 0.5 ppm O3 than depression of tracheal mucous velocity.

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.

Sign in / Sign up

Export Citation Format

Share Document