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 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 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.

Evidence for a direct action of acetylcholine on the gastric oxyntic cell of the amphibian

1984 ◽  
Vol 246 (1) ◽  
pp. G16-G25 ◽  
Author(s):  
M. C. Ruiz ◽  
F. Michelangeli
Keyword(s):  
Histamine Release ◽  
Dose Response ◽  
Direct Action ◽  
Second Messengers ◽  
Response Curves ◽  
Experimental Conditions ◽  
Oxyntic Cell ◽  
Endogenous Histamine ◽  
Dual Action ◽  
Dose Response Curves

The possibility of a direct action of acetylcholine (ACh) on the oxyntic cell not mediated by histamine release was studied in resting isolated gastric mucosae. H+ secretion and histamine release, and their relationship, were studied under ACh stimulation and other conditions. ACh released histamine from mucosal stores and stimulated H+ secretion. H2-receptor blocker cimetidine largely inhibited ACh-induced stimulation of H+ transport but not histamine release. Atropine inhibited the cholinergic response in both histamine release and H+ secretion. The dose-response curves to ACh showed nonparallel increases in H+ secretion and histamine release. When dose-response curves to exogenous and endogenous histamine (released by ACh) were compared, it was found that ACh increased Vmax for endogenous histamine. Comparison of the effects of ACh with other experimental conditions such as tetragastrin treatment, K+ depolarization, or Na+-free nutrient solution showed that the amount of histamine released by ACh was insufficient to explain the observed rates of secretion. Stimulation by ACh was faster, greater, and more transitory compared with that by histamine. In mucosae maximally stimulated by histamine, ACh induced a further increase in H+ secretion. In the presence of cimetidine, potentiation between ACh and dibutyryl cAMP or isobutyl-methylxanthine was found. The results are consistent with ACh having a dual action on oxyntic and histamine-releasing cells. The action of ACh on the oxyntic cell would potentiate the effect of released histamine. It is suggested that ACh and released histamine act on the oxyntic cell through different second messengers, resulting in the potentiated response.

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.

Relationship among sensitivity to adrenaline, plasma corticosterone level; and estrous cycle in rats

1995 ◽  
Vol 73 (5) ◽  
pp. 602-607 ◽  
Author(s):  
M. L. V. Rodrigues ◽  
F. K. Marcondes ◽  
R. C. Spadari-Bratfisch
Keyword(s):  
Estrous Cycle ◽  
Dose Response ◽  
Corticosterone Level ◽  
Plasma Corticosterone ◽  
Female Rats ◽  
Extraneuronal Uptake ◽  
Response Curves ◽  
Experimental Conditions ◽  
Dose Response Curves ◽  
Right Atria

The dose–response curves to the chronotropic effect of adrenaline obtained in right atria isolated from female rats indicated an order of increasing sensitivity to adrenaline, at the pD2 level, according to the estrous cycle, as follows: estrus ≤ metestrus ≤ diestrus ≤ proestrus. Inhibition of neuronal and extraneuronal uptake shifted the dose–response curves to adrenaline to the left only in right atria isolated from rats during estrus or metestrus. Moreover, under these experimental conditions, right atria were subsensitive to adrenaline during proestrus, in contrast to metestrus. Plasma corticosterone levels were lower during estrus and higher at proestrus. There was a positive correlation between right atria sensitivity to adrenaline and plasma corticosterone levels and estrous cycle phases. Our results also suggest that in the rat right atria during proestrus, as opposed to the other phases of the estrous cycle, there was an endogenous inhibition of extraneuronal uptake together with some alteration at the adrenoceptor level and (or) at intracellular mechanisms beyond receptors.Key words: adrenergic response, female, adrenaline, chronotropism, right atria.

STUDIES ON THE PITUITARY MELANOPHORE-EXPANDING HORMONE WITH REFERENCE TO ITS IDENTITY WITH ACTH

1954 ◽  
Vol 11 (1) ◽  
pp. 7-13 ◽  
Author(s):  
B. KETTERER ◽  
ELIZABETH REMILTON
Keyword(s):  
Linear Regression ◽  
Dose Response ◽  
Progressive Increase ◽  
Regression Curve ◽  
Response Curves ◽  
Experimental Conditions ◽  
Response Data ◽  
The Mean ◽  
Dose Response Curves ◽  
Linear Regression Curve

SUMMARY 1. The standard Xenopus method for the assay of pituitary melanophore-expanding hormone has been critically examined, and the results from various assay procedures are statistically analysed. 2. Log dose-response data are well fitted by a linear regression curve. Responses at 3 hr give a steeper curve than those at 1½ hr. 3. Results collected 6 months apart show that the mean and slope of dose-response curves remain constant when Xenopus are given regular dosage; there is, however, a progressive increase of variance with time shown by the colony under these experimental conditions. 4. Evidence is presented to show that Xenopus must be minimally disturbed during assay, and that assay doses must be given not less than 1 day apart.

Analysis and comparison of sigmoidal curves: application to dose-response data

1989 ◽  
Vol 257 (6) ◽  
pp. G982-G989 ◽  
Author(s):  
J. B. Meddings ◽  
R. B. Scott ◽  
G. H. Fick
Keyword(s):  
Nonlinear Regression ◽  
Dose Response ◽  
Numerical Solutions ◽  
Maximal Response ◽  
Response Curves ◽  
Experimental Conditions ◽  
Response Data ◽  
Accuracy And Precision ◽  
Analysis Technique ◽  
Dose Response Curves

A number of physiological or pharmacological studies generate sigmoidal dose-response curves. Ideally, data analysis should provide numerical solutions for curve parameters. In addition, for curves obtained under different experimental conditions, testing for significant differences should be easily performed. We have reviewed the literature over the past 3 years in six journals publishing papers in the field of gastrointestinal physiology and established the curve analysis technique used in each. Using simulated experimental data of known error structure, we have compared these techniques with nonlinear regression analysis. In terms of their ability to provide accurate estimates of ED50 and maximal response, none approached the accuracy and precision of nonlinear regression. This technique is as easily performed as the classic methods and additionally provides an opportunity for rigorous statistical analysis of data. We present a method of determining the significance of differences found in the ED50 and maximal response under different experimental conditions. The method is versatile and applicable to a variety of different physiological and pharmacological dose-response curves.

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.

Vasodilative and anti-adrenergic effects of adenosine in diabetic rat hearts

1992 ◽  
Vol 70 (1) ◽  
pp. 13-19 ◽  
Author(s):  
Eve L. Warner ◽  
Franco Galasso ◽  
Carl I. Thompson ◽  
Francis L. Belloni
Keyword(s):  
Diabetes Mellitus ◽  
Coronary Flow ◽  
Experimental Diabetes ◽  
Myocardial Contraction ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Diabetic Rat ◽  
Inotropic Effects ◽  
Isolated Hearts ◽  
Negative Inotropic Effects

To determine the vasodilative and negative inotropic effects of adenosine in hearts of diabetic rats, isolated hearts, perfused at constant perfusion pressure (Langendorff technique), were prepared from age-matched control Wistar rats and rats made diabetic 10 weeks prior to study by a single injection of streptozotocin (65 mg∙kg−1, i.p.). Adenosine and nitroprusside each increased coronary inflow when administered either as bolus injections or as infusions. Coronary flow responses to nitroprusside were unchanged in diabetic hearts. Coronary flow responses of diabetic hearts to adenosine injections were unchanged, but responses to adenosine infusions tended to be larger than in normal hearts. Diabetes had no significant effect on the EC50 for either vasodilator. Adenosine inhibited the inotropic effect of isoproterenol (enhanced left ventricular (LV) pressure (P) and LV dP/dtmax) in normal hearts, independently of its vasodilative action. This negative inotropic action of adenosine appeared equally strong in diabetic hearts. We conclude that adenosine's coronary vasodilative and anti-β-adrenergic, negative inotropic effects in the rat heart were not diminished after 10 weeks of streptozotocin-induced diabetes mellitus. Thus, earlier reports of diminished adenosine dilative efficacy in experimental diabetes may have been unique to those particular models.Key words: experimental diabetes mellitus, coronary, adenosine, isoproterenol, myocardial contraction.

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