scholarly journals Attenuation of Thrombosis by Crude Rice (Oryza sativa) Bran Policosanol Extract:Ex VivoPlatelet Aggregation and Serum Levels of Arachidonic Acid Metabolites

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Wai-Teng Wong ◽  
Maznah Ismail ◽  
Eusni Rahayu Mohd Tohit ◽  
Rasedee Abdullah ◽  
Yi-Da Zhang
Keyword(s):  
Platelet Aggregation ◽  
Rice Bran ◽  
Low Dose ◽  
Ex Vivo ◽  
Vascular Occlusion ◽  
Full Blood Count ◽  
Tween 20 ◽  
High Dose ◽  
Sprague Dawley ◽  
Coagulation Time

Background. Vascular occlusion or thrombosis was often attributed to uncontrolled platelet activation. Influence of sugarcane policosanol extract on platelet was reported but little was known of rice bran policosanol, particularly its mechanisms of actions on platelet activities.Objective. Antiplatelet mechanisms of rice bran policosanol extract (RBE) were studied using hyperlipidemic Sprague Dawley rats.Ex vivoplatelet aggregation, platelet count (PC), bleeding time (BT), and coagulation time were assayed. Serum eicosanoids and other aggregation-related metabolites levels were quantified.Design. Rats were divided into 6 groups for comparisons (vehicle control Tween 20/H2O, high dose policosanol 500 mg/kg, middle dose policosanol 250 mg/kg, low dose policosanol 100 mg/kg, and positive control aspirin 30 mg/kg).Results. Low dose 100 mg/kg of RBE inhibited aggregation by42.32±4.31% and this was comparable with the effect of 30 mg/kg aspirin,43.91±5.27%. Results showed that there were no significant differences in PC, BT, and coagulation time among various groups after RBE treatment. Serum thromboxane A2was attenuated while prostacyclin level increased upon RBE treatment.Conclusions. RBE reducedex vivoADP-induced platelet aggregation without giving adverse effects. No changes in full blood count suggested that rice bran policosanol did not disturb biological blood cell production and destruction yet it reduced aggregation through different mechanisms.

Benefit/Risk Profile of Combined Antiplatelet Therapy with Ticlopidine and Aspirin

1991 ◽  
Vol 65 (05) ◽  
pp. 504-510 ◽  
Author(s):  
Raffaele De Caterina ◽  
Rosa Sicari ◽  
Walter Bernini ◽  
Guido Lazzerini ◽  
Giuliana Buti Strata ◽  
...  
Keyword(s):  
Platelet Function ◽  
Low Dose ◽  
Bleeding Time ◽  
Ex Vivo ◽  
Stable Coronary Artery Disease ◽  
High Dose ◽  
Single Drug ◽  
Before And After ◽  
Serum Thromboxane ◽  
Artery Disease

SummaryTiclopidine (T) and aspirin (ASA) are two antiplatelet drugs both capable of prolonging bleeding time (BT), with a different mechanism of action. A synergism in BT prolongation has been reported and is currently considered an argument for not recommending their combination. However, a profound suppression of platelet function might be a desirable counterpart of a marked prolongation of BT, with a possible use in selected clinical situations. We therefore studied ex vivo platelet function (aggregation by ADP 0.5-1-2.5 μM; adrenaline 0.75-2.5 μM; collagen 1.5-150 μg/ml; arachidonic acid 1 mM; PAF 1 μM; adrenaline 0.17 μM + ADP 0.62 μM; serum thromboxane ([TX]B2 generation) and BT (Mielke) in 6 patients with stable coronary artery disease receiving such combination. Patients underwent sequential laboratory evaluations at baseline, after 7 days of T 250 mg b.i.d., before and after the intravenous administration of ASA 500 mg, respectively, and, finally, after a minimum of 7 days of sole ASA oral administration (50 mg/day). The experimental design, therefore, allowed a comparison of T and ASA effects (2nd and 4th evaluation), and an assessment of the combination effect (3rd evaluation). Platelet aggregation in response to all doses of ADP was depressed more by T than by ASA. Conversely, responses to adrenaline, and arachidonate were affected more by ASA than by T. For all other agents, differences were not significant. T + ASA combination was more effective (p <0.05) than either treatment alone in depressing responses to high-dose collagen (% over control, mean ± SEM: T: 95 ± 3; ASA: 96 ± 5; T + ASA: 89 ± 4). Serum TXB2 (basal, ng/ml: 380 ± 54) did not change with T (372 ± 36), dropped to <1 ng/ml on ASA injection and slightly re-increased to 9.1 ± 3.1 ng/ml on oral low-dose ASA. BT (basal 7.4 ± 0.6 min) was affected similarly by T (9.2 ± 0.8) or ASA (9.7 ± 0.9) alone, but increased to 15.0 ± 0.7 min on combination treatment (106% increase over control). Thus, the strong synergism in BT prolongation by ASA-T combination has a counterpart in the inhibition of platelet function in response to strong stimuli such as high-dose collagen, not otherwise affected significantly by single-drug treatment. This effect is a possible rationale for the clinical evaluation of T + ASA combination.

Effects of Aspirin and Sulfinpyrazone on Thromboxane and Prostacyclin Synthesis in Rabbits

1979 ◽  
Author(s):  
J McDonald ◽  
A Cerskus ◽  
M Ali
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Low Dose ◽  
High Dose ◽  
Prostacyclin Synthesis

Arachidonic acid (AA) or collagen were infused into rabbits causing intravascular platelet aggregation with thrombocytopenia, hypotension and death. Thromboxane and prostacyclin synthesis were measured by radioimmunoassay of plasma TXB2 and 6-keto-PGF1α. The effects of pretreatement with aspirin (ASA) or sulfinpyrazone(SPZ) were assessed.Death in drug-treated rabbits was always associated with elevations of plasma TXB2(1-40 ng/ml) and of 6-keto-PGF1α(1-20 ng/ml). Collagen produced only small elevations of plasma TXB2 compared to AA but protection by ASA correlated better with inhibition of TXB2 and 6-keto-PGF1α synthesis than with inhibition of aggregation. Low dose ASA produced less inhibition of prostacyclin synthesis than high dose ASA but was less effective in preventing thromboxane synthesis and death.

Ferulic Acid Dose Effect on Pharmacokinetics of Glimepiride and its Metabolite Hydroxy Glimepiride in Rats

2021 ◽  
Vol 17 ◽  
Author(s):  
Yuxian Lin ◽  
Faxin Sun ◽  
Jinlai Liu ◽  
Qinghua Weng ◽  
Lijun Jin ◽  
...  
Keyword(s):  
Ferulic Acid ◽  
Low Dose ◽  
Dose Effect ◽  
High Dose ◽  
Intragastric Administration ◽  
Healthy Male ◽  
Sprague Dawley ◽  
Sd Rats ◽  
High Dose Treatment ◽  
Significant Difference

Background: To mitigate diabetes and its complications in cardiovascular diseases, the antidiabetic agent glimepiride is usually administered with ferulic acid concomitantly in clinics. However, both drugs are prone to be metabolized partly by CYP2C9, thus they have the potential drug-drug interaction affecting the safety and efficacy. Objective: This project aimed to evaluate the pharmacokinetic (PK) effects of ferulic acid (FA) on glimepiride (GLM) and its metabolite hydroxy glimepiride (OH-GLM) in plasma by using the HPLC-MS/MS method. Methods: Healthy male Sprague Dawley (SD) rats were randomly divided into three groups. They received intragastric administration of 0.5% sodium carboxymethyl cellulose (CMC), low-dose FA (20 mg•kg-1), and high-dose FA (40 mg•kg-1) for 8 days, respectively. Rats were given 0.5% sodium CMC or FA on the last day and then uniformly given 1.0 mg•kg-1 glimepiride by gavage. Blood samples were obtained from retro-orbital plexus at the time points of 0.167, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 h after administration. Plasma samples were analyzed for GLM and its metabolite OH-GLM on an HPLC-MS/MS system. Results: No statistically significant difference was found in the effect of low-dose FA on the pharmacokinetics of GLM. High-dose FA significantly decreased Cmax of GLM by 30.05% and CLz/F of OH-GLM by 47.45%. It also increased Tmax and t1/2z of GLM by 95.87% and 140.00%. Conclusion: Low-dose FA did not alter GLM metabolism, while high-dose treatment of FA caused pharmacokinetics interaction with GLM in rats.

Effects of Aspirin and Sulfinpyrazone on Thromboxane and Prostacyclin Synthesis in Rabbits

1979 ◽  
Author(s):  
J.W.D. McDonald ◽  
A.L. Cerskus ◽  
M. Ali
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Low Dose ◽  
High Dose ◽  
Prostacyclin Synthesis

Arachidonic acid (AA) or collagen were infused into rabbits causing intravascular platelet aggregation with thrombocytopenia, hypotension and death. Thromboxane and prostacyclin synthesis were measured by radioimmunoassay of plasma TXB2 and 6-keto-PCF1α. The effects of pretreatment with aspirin (ASA) or sulfinpyrazone (SPZ) were assessed.Death in drug-treated rabbits was always associated with elevations of plasma TXB2 (1-40 ng/ml) and of 6-keto-PGF1α (1-20 ng/ml). Collagen produced only small elevations of plasma TXB2 compared to AA but protection by ASA correlated better with inhibition of TXB2 and 6-keto-PGF1α synthesis than with inhibition of aggregation. Low dose ASA produced less inhibition of prostacyclin synthesis than high dose ASA but was less effective in preventing thromboxane synthesis and death.

Potent low dose platelet inhibitory effects of clopidogrel and aspirin on coronary thrombus formation in an animal model of acute unstable angina

2006 ◽  
Vol 95 (02) ◽  
pp. 354-361 ◽  
Author(s):  
Oliver Berg ◽  
Axel Heimann ◽  
Thomas Münzel ◽  
Christian-Friedrich Vahl ◽  
Oliver Kempski ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Low Dose ◽  
Thrombus Formation ◽  
Drug Application ◽  
Bleeding Complications ◽  
High Dose ◽  
Cardiac Events ◽  
Coronary Syndrome ◽  
Dose Combination

SummaryApplication of clopidogrel before percutaneous coronary intervention in patients with acute coronary syndrome reduces the risk of cardiac events. Clopidogrel administration before surgery increases bleeding complications after CABG. Therefore, the antithrombotic effect of the low-dose combination of clopidogrel and aspirin was investigated in an in vivo pig model of coronary artery thrombus formation with cyclic flow reductions. The platelet inhibitory effect was determined by platelet aggregation and CFR, according to the methodology described by Folts. CFR were initiated by endothelial damage and placement of a constrictor around the LAD. 30 min after CFR were established, clopidogrel (0.1 mg/kg or5 mg/kg), aspirin (1 mg/kg or 7 mg/kg) or LDC (0.1 mg/kg clopidogrel and 1 mg/kg aspirin) were administered orally. CFR-frequency was determined for further 240 min. CFR-frequency (CFR/30 min) was significantly reduced at 60 min in response to aspirin (7 mg/kg, −48%, p<0.05), and at 120 min in response to clopidogrel (5 mg/kg, −65%, p<0.05) but not at low doses of either compound. In contrast, LDC of clopidogrel (0.1 mg/kg) plus aspirin (1 mg/kg) resulted in a complete and rapid abrogation of CFR at 90 min (−70%, p<0.05). Furthermore, LDC led to reduction of platelet aggregation when CFR-frequency was already significantly decreased. In contrast, high dose groups presented a significant reduction of platelet aggregation prior to CFR-frequency decrease. Low dose combination of clopidogrel plus aspirin demonstrates a potent over additive anti-thrombotic effect in vivo with a significant reduction in thrombus formation early after drug application. The effect occurs before inhibition of platelet aggregation is detectable.

scholarly journals Original Article. Inflammatory effect of 2-aminoanthracene (2AA) on adipose tissue gene expression in pregnant Sprague Dawley rats

2016 ◽  
Vol 9 (1) ◽  
pp. 17-24
Author(s):  
Shamaya L. Whitby ◽  
Daniel A. Hunter ◽  
Wilson Yau ◽  
Elizabeth W. Howerth ◽  
Worlanyo E. Gato
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Dose Group ◽  
Low Dose ◽  
Mononuclear Cells ◽  
Postnatal Period ◽  
High Dose ◽  
Sprague Dawley ◽  
Polycyclic Aromatic ◽  
Altered Gene

Abstract Adipocyte dysfunction may be a critical link between obesity and insulin resistance as a result of abnormal fat storage and mobilization. Adipocytes uniquely secrete adipokines and cytokines, such as leptin and TNFα, wich promote insulin sensitivity. Previously we reported insulin-signaling related altered gene expression in animals exposed to 2-Aminoanthracene (2AA). 2AA is an aminosubstituted polycyclic aromatic hydrocarbon used in manufacturing dyes, chemicals, inks, resins, and polyurethanes. The objective of this study was to examine the inflammation related effects of 2AA exposure from gestation to postnatal period on dams that ingested 2AA. To examine 2AA effects, pregnant dams were assigned into dose regimens of 2AA. Dams were fed 2AA contaminated diet during the period of gestation and postpartum. The expression of key gene transcripts reported to be important in mediating inflammatory processes was examined via quantitative RT-PCR. Histologic examination of adipose tissue (AT) was also carried out to understand the anatomy of AT due to 2AA exposure during gestation and two weeks postpartum. Examination of the adipose tissue for microscopic changes revealed no alterations between control and low-dose animals. However, AT of the high-dose animals was infiltrated by increased numbers of CD68+mononuclear cells (macrophages) and small numbers of eosinophils and mast cells, consistent with inflammation. In addition, analysis of the mRNA expression of cytokines and adipokines demonstrated the importance of inflammation in AT dysfunction. For instance, TNFα, LEPTIN and IL-6 transcripts were relatively more expressed in the low dose animals than in the high dose and control rats. At the protein level, however, high amounts of cytokines were noted. The effects of 2AA on pregnant dams appear to be more pronounced in the high dose group than in the low dose group, possibly indicating increased susceptibility of rat offspring within this group to elicit a diabetic-type response.

scholarly journals Blood Biochemical and Hematological Study after Subacute Intravenous Injection of Gold and Silver Nanoparticles and Coadministered Gold and Silver Nanoparticles of Similar Sizes

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Ji Hyun Lee ◽  
Mary Gulumian ◽  
Elaine M. Faustman ◽  
Tomomi Workman ◽  
KiSoo Jeon ◽  
...  
Keyword(s):  
Silver Nanoparticles ◽  
Low Dose ◽  
Systemic Toxicity ◽  
Blood Biochemistry ◽  
Control Group ◽  
High Dose ◽  
Sprague Dawley ◽  
Gold And Silver Nanoparticles ◽  
Blood Biochemical ◽  
Active Partial Thromboplastin Time

Background. To investigate the effect of subacute intravenous administration AgNP (silver nanoparticles, 10 nm) and AuNP (gold nanoparticles, 12.8 nm) and AgNP/AuNP mixture to blood biochemistry, hematology, and platelet coagulation, subacute toxicity study was conducted. Methods. AuNP and AgNP in which their size distribution was not statistically different, mixed or separate, were injected into the caudal vein of male Sprague-Dawley rats for 4 weeks. The rats were allowed to recover for a further 4 weeks in order to examine systemic toxicity expressed in the blood biochemistry and hematology. The dose groups (5 males per group for the administration and 3 males for the recovery) consisted of 7 divisions, i.e., control, AgNP (with a low dose of 10 μg/kg/day and a high dose of 100 μg/kg/day), AuNP (with a low dose of 10 μg/kg/day and a high dose of 100 μg/kg/day), and mixed AgNP/AuNP (with a low dose of 10/10 μg/kg/day and a high dose of 100/100 μg/kg/day). Results. There were no significant dose-related changes in the hematology and blood biochemical values for the rats. Coagulation time in terms of the active partial thromboplastin time (APTT) and prothrombin time (PT) did not show any significant changes, when compared to the control group. Conclusion. The subacute injection of AuNP and AgNP or their mixture did not induce any noticeable systemic toxicity.

AR-H067637, the Active Metabolite of the Oral Anticoagulant AZD0837, with and without Aspirin or Aspirin and Clopidogrel in Experimental Models of Venous and Arterial Thrombosis and Bleeding in Anaesthetized Rats

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5459-5459
Author(s):  
Margareta Elg ◽  
Anna Rönnborg ◽  
Magnus Kjaer
Keyword(s):  
Platelet Aggregation ◽  
Ferric Chloride ◽  
Arterial Thrombosis ◽  
Peak Concentration ◽  
Low Dose ◽  
Saline Group ◽  
Vehicle Group ◽  
Impedance Method ◽  
High Dose ◽  
Anaesthetized Rats

Abstract AR-H067637 is a direct thrombin inhibitor derived in vivo from the orally available prodrug AZD0837. AZD0837 is in development for use in thromboembolic disorders. This study investigated the additional effects of aspirin (ASA) alone and in combination with clopidogrel (Clop) on AR-H067637 in animal models of venous thrombosis (VT) and arterial thrombosis (AT). Anaesthetized rats (9–11 per treatment group) were treated with vehicle or 3 increasing (low, middle and high) doses of AR-H067637 (0.1, 0.3 and 1.0 μmol/kg/h in VT model and 0.5, 1.5 and 4.5 μmol/kg/h in AT model [predicted to obtain 25%, 50% and 75% antithrombotic effect]) given intravenously (iv) as continuous infusions. Rats were also treated with saline, ASA (10mg/kg) or ASA (10mg/kg) + Clop (25mg/kg) as iv bolus injections at the start of the experiment. In the AT model the thrombotic stimulus was ferric chloride administered to the carotid artery, while in the VT model the stimulus was ferric chloride and partial stasis of the caval vein. Thrombus size (TS) was assessed as wet weight (both models) and as protein content (AT model only). Bleeding time (BT) and blood loss (BL) were investigated by tail incision (TI) and muscle transection (MT). Activated partial thromboplastin time (APTT; AT model), thrombin coagulation time (TcT; AT model), thrombin generation (determined using the calibrated automatic thrombogram [CAT] assay variables; both models), lag time (LT), time to peak concentration (ttPeak), peak concentration (peak) and endogenous thrombin potential (ETP) were investigated. Arachidonic acid (AA) and ADP-induced platelet aggregation were measured by the whole blood impedance method in a subset of rats (n=6) to verify antiplatelet effects of ASA and Clop, respectively. Results showed that ARH067637 dose-dependently decreased TS in both models (Table). ASA+Clop, decreased TS in both models. In the VT model, ASA+Clop had no additional effect to that seen with AR-H067637 alone, but in the AT model further decreased TS with total inhibition obtained at the highest dose of AR-H067637. AR-H067637 dose-dependently prolonged TI BT and BL and MT BL (up to 2.4, 1.4 & 2.1 times the vehicle group). ASA in addition to AR-H067637 did not potentiate TI BT or MT BL but potentiated TI BL in addition to the highest dose of AR-H067637. ASA+Clop potentiated TI BT, BL and MT BL (2.6, 5.4 & 2.4 times the saline group). Only high-dose AR-H067637 reinforced this bleeding (TI BT and BL and MT BL 3.4, 17 and 9.2 times the saline group). AR-H067637 concentration-dependently prolonged TcT (2–7 times), APTT (1.3–3 times), CAT LT (up to 2.6 times), CAT ttPeak (up to 2 times), and the highest plasma concentration totally abolished CAT peak and CAT ETP. ASA or ASA+Clop had no influence on these variables. AA and ADP-induced platelet aggregation was inhibited by 96% in ASA-treated and 29% in Clop-treated animals, respectively. This investigation shows that ASA with or without ARH067637 had a small effect on TS, without increasing bleeding. ASA+Clop decreased TS: effects were more marked in the AT model, but increased bleeding was seen, especially at high AR-H067637 plasma concentrations. Pharmacodynamic markers indicate dose-dependant, increased anticoagulation with rising concentrations of AR-H067637; these markers were not influenced by ASA or ASA+Clop. Thrombus size (TS) in VT and AT models TS in VT (%) TS in AT (%) AR-H=AR-H067637; LD=low dose; MD=middle dose; HD=high dose Controls 100±8 100±9 Saline + ASA 89±9 71±10 Saline + ASA/Clop 73±7 64±11 Low dose (LD) LD AR-H 62±11 82±9 LD AR-H + ASA 72±11 77±8 LD AR-H + ASA/Clop 67±9 36±8 Middle dose (MD) MD AR-H 49±6 64±9 MD AR-H + ASA 46±10 51±6 MD AR-H + ASA/Clop 32±9 34±6 High-dose (HD) HD AR-H 12±3 23±5 HD AR-H + ASA 12±2 27±6 HD AR-H + ASA/Clop 10±1 1±1

scholarly journals Therapeutic Effects of Water Soluble Danshen Extracts on Atherosclerosis

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Yoon Hee Cho ◽  
Cheol Ryong Ku ◽  
Zhen-Yu Hong ◽  
Ji Hoe Heo ◽  
Eun Hee Kim ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Platelet Aggregation ◽  
Ex Vivo ◽  
Umbilical Vein ◽  
Water Soluble ◽  
Therapeutic Effects ◽  
Sprague Dawley ◽  
Tail Vein ◽  
Vein Thrombosis

Danshen is a traditional Chinese medicine with many beneficial effects on cardiovascular diseases. The aim of this study was to evaluate the mechanisms responsible for the antiatherogenic effect of water soluble Danshen extracts (DEs). Rat vascular smooth muscle cells (VSMCs) and human umbilical vein endothelial cells (HUVECs) were treated with DE. To evaluate the effects of DEin vivo, carotid balloon injury and tail vein thrombosis were induced in Sprague-Dawley (SD) rats and iliac artery stent was induced in New Zealand white rabbits. The inhibitory action of DE on platelet aggregation was confirmed with an impedance aggregometer. DE inhibited the production of reactive oxygen species, and the migration and proliferation of platelet-derived growth factor-BB stimulated VSMCs. Furthermore, DE prevented inflammation and apoptosis in HUVECs. Both effects of DE were reconfirmed in both rat models. DE treatment attenuated platelet aggregation in bothin vivoandex vivoconditions. Pretreatment with DE prevented tail vein thrombosis, which is normally induced byκ-carrageenan injection. Lastly, DE-treated rabbits showed decreased in-stent restenosis of stented iliac arteries. These results suggest that water soluble DE modulates key atherogenic events in VSMCs, endothelial cells, and platelets in bothin vitroandin vivoconditions.

Sympathetic and parasympathetic component of bradycardia triggered by stimulation of NTS P2X receptors

2006 ◽  
Vol 290 (2) ◽  
pp. H807-H812 ◽  
Author(s):  
Amy M. Kitchen ◽  
Donal S. O'Leary ◽  
Tadeusz J. Scislo
Keyword(s):  
Low Dose ◽  
Nucleus Tractus Solitarius ◽  
Receptor Activation ◽  
P2x Receptors ◽  
P2x Receptor ◽  
High Dose ◽  
Adrenergic Blockade ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Stimulation Of

We have previously shown that activation of P2X purinoceptors in the subpostremal nucleus tractus solitarius (NTS) produces a rapid bradycardia and hypotension. This bradycardia could occur via sympathetic withdrawal, parasympathetic activation, or a combination of both mechanisms. Thus we investigated the relative roles of parasympathetic activation and sympathetic withdrawal in mediating this bradycardia in chloralose-urethane anesthetized male Sprague-Dawley rats. Microinjections of the selective P2X purinoceptor agonist α,β-methylene ATP (25 pmol/50 nl and 100 pmol/50 nl) were made into the subpostremal NTS in control animals, after atenolol (2 mg/kg iv), a β1-selective antagonist, and after atropine methyl bromide (2 mg/kg iv), a muscarinic receptor antagonist. The bradycardia observed with activation of P2X receptors at the low dose of the agonist is mediated almost entirely by sympathetic withdrawal. After β1-adrenergic blockade, the bradycardia was reduced to just −5.1 ± 0.5 versus −28.8 ± 5.1 beats/min in intact animals. Muscarinic blockade did not produce any significant change in the bradycardic response at the low dose. At the high dose, both β1-adrenergic blockade and muscarinic blockade attenuated the bradycardia similarly, −37.4 ± 6.4 and −40.6 ± 3.7 beats/min, respectively, compared with −88.0 ± 11 beats/min in control animals. Double blockade of both β1-adrenergic and muscarinic receptors virtually abolished the response (−2.5 ± 0.8 beats/min). We conclude that the relative contributions of parasympathetic activation and sympathetic withdrawal are dependent on the extent of P2X receptor activation.

Sign in / Sign up

Export Citation Format

Share Document