Neither endogenous nor inhaled nitric oxide influences the function of circulating platelets in healthy volunteers

1999 ◽  
Vol 97 (3) ◽  
pp. 345-353 ◽  
Author(s):  
Johanna ALBERT ◽  
N. Håkan WALLÉN ◽  
Nailin LI ◽  
Claes FROSTELL ◽  
Paul HJEMDAHL
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Heart Rate ◽  
Healthy Volunteers ◽  
Thrombin Generation ◽  
Bleeding Time ◽  
Flow Cytometric ◽  
Fibrinogen Binding ◽  
Inhaled No

Experimental models have indicated prothrombotic effects of inhibition of nitric oxide (NO) production, and anti-thrombotic effects of inhaled NO, but the influence of NO on platelet function in vivo in humans is not well established. We therefore investigated the effects of systemic inhibition of NO synthesis by NG-monomethyl-⌊-arginine (⌊-NMMA) and of NO inhalation on platelet function in vivo. On two occasions, ⌊-NMMA (13.5 mg/kg) or saline infusion was administered to 14 healthy volunteers in a double-blind cross-over study. After a 30 min infusion of ⌊-NMMA or placebo, NO inhalation (30 p.p.m) was added during the remaining 30 min of infusion, on both occasions. Measurements included filtragometry ex vivo (reflecting platelet aggregability), flow-cytometric evaluation of platelets in whole blood (fibrinogen binding and P-selectin expression), plasma β-thromboglobulin (reflecting platelet secretion), cGMP in platelets and plasma, thrombin generation markers (thrombin fragment 1+2 and thrombin–antithrombin complexes) in plasma, and bleeding time. l-NMMA increased blood pressure and decreased heart rate. NO inhalation did not influence blood pressure or heart rate, but caused a 3-fold elevation in plasma cGMP levels (P < 0.001). Neither ⌊-NMMA nor NO influenced filtragometry readings or flow-cytometric determinations of platelet fibrinogen binding and P-selectin expression. Furthermore, plasma β-thromboglobulin, platelet cGMP and thrombin generation markers were not influenced by either treatment. Bleeding time was not influenced by ⌊-NMMA compared with placebo, but was increased by ≈ 25% during NO inhalation (P < 0.01), whether NO synthesis had been inhibited or not. The prolongation of bleeding time by inhaled NO was not accompanied by any effect on the platelet variables assessed. The present results indicate that circulating platelets are not influenced by endogenous or inhaled NO, presumably due to the rapid inactivation of NO in the blood. This does not exclude possible effects of endothelial NO in the interface between the blood and the vessel wall.

Randomized, Placebo-controlled, Blinded and Cross-matched Study on the Antiplatelet Effect of Inhaled Nitric Oxide in Healthy Volunteers

2000 ◽  
Vol 83 (02) ◽  
pp. 309-315 ◽  
Author(s):  
Axel Herr ◽  
Johann Motsch ◽  
Alexandra Holzmann ◽  
Jörg Weimann ◽  
Friedemann Taut ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Platelet Aggregation ◽  
Healthy Volunteers ◽  
Bleeding Time ◽  
Inhibitory Effect ◽  
Inhaled Nitric Oxide ◽  
Men And Women ◽  
Fibrinogen Binding ◽  
Matched Study

SummaryThe platelet inhibitory effect of 0-40 ppm inhaled nitric oxide (NO) was investigated in healthy men and women. In both groups, ADPand collagen-induced platelet aggregation was significantly inhibited 20 (T20) and 40 min (T40) after the beginning of inhalation of 5, 10, and 40 ppm. Moreover, in both men and women, the in vitro bleeding time was significantly prolonged at T20 and T40 during inhalation of 40 ppm. Inhalation of NO also inhibited P-selectin expression at 5, 10, and 40 ppm and fibrinogen binding to the GPIIb/IIIa-receptor at 40 ppm. In conclusion, in healthy volunteers, the platelet inhibitory effect of inhaled NO was not dose-related, since it was significant at 5 and 10 ppm but did not increase during the administration of higher NO concentrations. In addition, gender-related differences were only observed in ADP-induced platelet aggregation at 10 ppm and in bleeding time prolongation at 40 ppm.

scholarly journals Rosuvastatin Decreases Caveolin-1 and Improves Nitric Oxide–Dependent Heart Rate and Blood Pressure Variability in Apolipoprotein E −/− Mice In Vivo

Circulation ◽  
2003 ◽  
Vol 107 (19) ◽  
pp. 2480-2486 ◽  
Author(s):  
Michel Pelat ◽  
Chantal Dessy ◽  
Paul Massion ◽  
Jean-Pierre Desager ◽  
Olivier Feron ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Heart Rate ◽  
Apolipoprotein E ◽  
Blood Pressure Variability ◽  
Caveolin 1

Investigation of the Interaction of Blood Platelets with the Coagulation System at the Site of Plug Formation In Vivo in Man - Effect of Low-Dose Aspirin

1987 ◽  
Vol 57 (01) ◽  
pp. 062-066 ◽  
Author(s):  
P A Kyrle ◽  
J Westwick ◽  
M F Scully ◽  
V V Kakkar ◽  
G P Lewis
Keyword(s):  
Platelet Activation ◽  
Thrombin Generation ◽  
Low Dose ◽  
Bleeding Time ◽  
Blood Platelets ◽  
Dose Aspirin ◽  
Low Dose Aspirin ◽  
Plug Formation ◽  
Granule Release

SummaryIn 7 healthy volunteers, formation of thrombin (represented by fibrinopeptide A (FPA) generation, α-granule release (represented by β-thromboglobulin [βTG] release) and the generation of thromboxane B2 (TxB2) were measured in vivo in blood emerging from a template bleeding time incision. At the site of plug formation, considerable platelet activation and thrombin generation were seen within the first minute, as indicated by a 110-fold, 50-fold and 30-fold increase of FPA, TxB2 and PTG over the corresponding plasma values. After a further increase of the markers in the subsequent 3 minutes, they reached a plateau during the fourth and fifth minute. A low-dose aspirin regimen (0.42 mg.kg-1.day-1 for 7 days) caused >90% inhibition of TxB2formation in both bleeding time blood and clotted blood. At the site of plug formation, a-granule release was substantially reduced within the first three minutes and thrombin generation was similarly inhibited. We conclude that (a) marked platelet activation and considerable thrombin generation occur in the early stages.of haemostasis, (b) α-granule release in vivo is partially dependent upon cyclo-oxygenase-controlled mechanisms and (c) thrombin generation at the site of plug formation is promoted by the activation of platelets.

Compression Stocking Length Effects on Arterial Blood Pressure and Heart Rate Following Head-Up Tilt in Healthy Volunteers

2014 ◽  
Vol 63 (6) ◽  
pp. 435-438 ◽  
Author(s):  
Kunihiko Tanaka ◽  
Shiori Tokumiya ◽  
Yumiko Ishihara ◽  
Yumiko Kohira ◽  
Tetsuro Katafuchi
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Healthy Volunteers ◽  
Arterial Blood Pressure ◽  
Compression Stocking ◽  
Arterial Blood ◽  
Head Up Tilt ◽  
Length Effects

Effects of S-adenosyl-methionine on plasma norepinephrine, blood pressure, and heart rate in healthy volunteers

1986 ◽  
Vol 17 (2) ◽  
pp. 111-118 ◽  
Author(s):  
Michael A. Sherer ◽  
Giulio L. Cantoni ◽  
Robert N. Golden ◽  
Matthew V. Rudorfer ◽  
William Z. Potter
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Healthy Volunteers ◽  
Plasma Norepinephrine ◽  
Adenosyl Methionine

Cardiovascular Responding during Anger and Fear Imagery

1982 ◽  
Vol 50 (1) ◽  
pp. 219-230 ◽  
Author(s):  
Richard J. Roberts ◽  
Theodore C. Weerts
Keyword(s):  
College Students ◽  
Blood Pressure ◽  
Heart Rate ◽  
Systolic Blood Pressure ◽  
Diastolic Blood Pressure ◽  
Scene Change ◽  
Emotional Responding ◽  
Analysis Of Change ◽  
Screening Interview

This study was designed to determine if visualization of anger- and fear-provoking scenes produced differential physiological patterns similar to those produced by in vivo manipulations. Normotensive college students were selected on the basis of their responses to newly developed Anger and Fear/Anxiety questionnaires and for their ability to construct arousing scenes during a screening interview. In a 2 × 2 design (intensity × emotion), four scenes (high and low anger, high and low fear) were constructed individually for each of 16 subjects to imagine. Diastolic blood pressure, systolic blood pressure, and heart rate were monitored during visualization of each scene. Change in diastolic blood pressure was significantly greater for high anger than for high fear as predicted. Analysis of change in heart rate and systolic blood pressure showed significant effects for intensity only. These results provide further support for the concept of physiological differentiation in human emotion and suggest the utility of imagery for systematic study of human emotional responding.

Comparative study on effect of neutral spinal bath and neutral spinal spray on blood pressure, heart rate and heart rate variability in healthy volunteers

2018 ◽  
Vol 16 (2) ◽  
Author(s):  
Arundhati Goley ◽  
A. Mooventhan ◽  
NK. Manjunath
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Heart Rate Variability ◽  
Healthy Volunteers ◽  
Group Analysis ◽  
Low Frequency ◽  
Single Session ◽  
Arterial Blood ◽  
Before And After ◽  
Instantaneous Heart Rate

Abstract Background Hydrotherapeutic applications to the head and spine have shown to improve cardiovascular and autonomic functions. There is lack of study reporting the effect of either neutral spinal bath (NSB) or neutral spinal spray (NSS). Hence, the present study was conducted to evaluate and compare the effects of both NSB and NSS in healthy volunteers. Methods Thirty healthy subjects were recruited and randomized into either neutral spinal bath group (NSBG) or neutral spinal spray group (NSSG). A single session of NSB, NSS was given for 15 min to the NSBG and NSSG, respectively. Assessments were taken before and after the interventions. Results Results of this study showed a significant reduction in low-frequency (LF) to high-frequency (HF) (LF/HF) ratio of heart rate variability (HRV) spectrum in NSBG compared with NSSG (p=0.026). Within-group analysis of both NSBG and NSSG showed a significant increase in the mean of the intervals between adjacent QRS complexes or the instantaneous heart rate (HR) (RRI) (p=0.002; p=0.009, respectively), along with a significant reduction in HR (p=0.002; p=0.004, respectively). But, a significant reduction in systolic blood pressure (SBP) (p=0.037) and pulse pressure (PP) (p=0.017) was observed in NSSG, while a significant reduction in diastolic blood pressure (DBP) (p=0.008), mean arterial blood pressure (MAP) (p=0.008) and LF/HF ratio (p=0.041) was observed in NSBG. Conclusion Results of the study suggest that 15 min of both NSB and NSS might be effective in reducing HR and improving HRV. However, NSS is particularly effective in reducing SBP and PP, while NSB is particularly effective in reducing DBP and MAP along with improving sympathovagal balance in healthy volunteers.

Abstract 1033: Simultaneous Clot-targeted Factor Xa Inhibition And Selective Blockade Of Activated GPIIb/IIIa On Platelets Results In Delayed But Potent Antithrombotic Effects Without Bleeding Time Prolongation.

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Christoph E Hagemeyer ◽  
Steffen U Eisenhardt ◽  
Nicole Bassler ◽  
Patrick Stoll ◽  
Meike Schwarz ◽  
...  
Keyword(s):  
Bleeding Time ◽  
Specific Binding ◽  
Factor Xa ◽  
Single Chain ◽  
Occlusion Time ◽  
Selective Blockade ◽  
Thrombosis Model ◽  
Fibrinogen Binding ◽  
Antithrombotic Effects

Background: We generated phage-display-derived anti-GPIIb/IIIa single-chain antibodies (e.g. scFv SCE5) that specifically bind to the activated GPIIb/IIIa only and thus specifically block activated platelets only. ScFv SCE5 demonstrates strong antithrombotic potency, comparable to the conformation-unspecific blockers tirofiban and eptifibatide. In contrast bleeding times were not prolonged with scFv SCE5. Here we now use the possibility to add effector molecules using molecular biology methods. The highly potent anticoagulant TAP (tick anticoagulant peptide), which is a direct factor Xa (fXa) inhibitor, was used as an effector molecule. Methods and Results: We genetically fused the activation-specific scFv with TAP, expressed the constructs in E.coli and purified the 39 kDa protein via its Histag binding to Nickel beads. Specific binding of the fusion molecules MA2/SCE5-TAP and strong inhibition of fibrinogen binding was proven in flow cytometry; anti-fXa activity was demonstrated in chromogenic assays. In vivo anticoagulative efficiency was determined by Doppler-flow in a ferric chloride-induced carotid artery thrombosis model in mice. Prolongation in occlusion time with SCE5-TAP was significantly stronger compared to SCE5 alone, recombinant TAP, non-binding mut-scFv-TAP as well as the clinical used drugs enoxaparine and eptifibatide. In contrast to the other anticoagulants tested, bleeding time was not prolonged by SCE5-TAP. Flow experiments studying platelet adhesion on collagen revealed a possible mechanism for the unique finding of a fully normal bleeding time: LIBS exposure on adhering platelets and as such the anticoagulative targeting potency of SCE5-TAP was delayed until considerable layers of platelets were deposited. Conclusions: The combination of activation-specific GPIIb/IIIa blockade and fXa inhibition in one clot-targeted molecule further improves in-vivo antithrombotic efficiency without causing any bleeding time prolongation. The delay of the observed targeting effect may allow a sealing of injuries with platelet layers but may be in time for the prevention of occlusive platelet aggregates. The described blockers represent a new type of highly selective drugs that warrant further clinical development.

Abstract P388: Extra-cardiac BCAA Catabolism Lowers Blood Pressure And Protects From Heart Failure

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Danielle Murashige ◽  
Cholsoon Jang ◽  
Michael Neinast ◽  
Michael Levin ◽  
Jae Woo Jung ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Heart Failure ◽  
Blood Pressure ◽  
Mendelian Randomization ◽  
Multiple Models ◽  
Direct Effects ◽  
Heavy Isotope ◽  
Branched Chain Amino Acid ◽  
Branched Chain

Pharmacologic activation of branched chain amino acid (BCAA) catabolism is protective in numerous models of heart failure (HF). How this protection occurs has remained unclear, although a causative block in cardiac BCAA oxidation has been proposed. We use here in vivo heavy isotope infusion studies to show that cardiac preference for BCAA oxidation increases, rather than decreases, in multiple models of HF. We use various genetic models to show that cardiac-specific activation of BCAA oxidation does not protect from HF, even though systemic activation of BCAA oxidation does. Lowering plasma and cardiac BCAAs by genetic means is also not sufficient to confer protection comparable to that conferred by pharmacologic activation of BCAA oxidation, suggesting alternative mechanisms of protection. Surprisingly, telemetry and invasive hemodynamic studies showed that pharmacological activation of BCAA catabolism lowers blood pressure, a well-established cardioprotective mechanism. The effects on blood pressure occurred independently of nitric oxide (NO), and reflected a vascular resistance to adrenergic constriction. Finally, mendelian randomization studies revealed that elevations in plasma BCAAs portend higher blood pressure in large human cohorts. Together, these data indicate that activation of BCAA oxidation lowers blood pressure and protects from heart failure independently of any direct effects on the heart itself.

Measurement of sympathetic nerve activity in the unanesthetized rat

1989 ◽  
Vol 67 (1) ◽  
pp. 250-255 ◽  
Author(s):  
J. P. Fluckiger ◽  
G. Gremaud ◽  
B. Waeber ◽  
A. Kulik ◽  
A. Ichino ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Arterial Pressure ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Blood Pressure Reduction ◽  
Response Curves ◽  
Nerve Activity ◽  
Dose Dependent

A new system was developed in our laboratory to continuously monitor intra-arterial pressure, heart rate, and sympathetic nerve activity in unanesthetized rats. The animals were prepared 24 h before the start of the experiments. Sympathoneural traffic was measured at the level of splanchnic nerve. The amplitude of the spikes recorded at this level was utilized to express sympathetic nerve activity. The amplitude of the residual electroneurogram signal present 30 min after the rats were killed was 32 +/- 2 mV (mean +/- SE; n = 11). For analysis, these background values were subtracted from values determined in vivo. The nerve we studied contains postganglionic fibers, since electrical activity decreased in response to ganglionic blockade with pentolinium (1.25 mg/min iv for 4 min). The amplitude of spikes fell by 43 +/- 4% (n = 4). Sympathetic nerve activity was highly reproducible at a 24-h interval (104 +/- 26 vs. 111 +/- 27 mV for the amplitude of spikes; n = 11). Dose-response curves to the alpha 1-stimulant methoxamine and to bradykinin were established in four rats. The increase in blood pressure induced by methoxamine caused a dose-dependent fall in sympathetic nerve activity, whereas the blood pressure reduction resulting from bradykinin was associated with a dose-dependent activation of sympathetic drive. These data therefore indicate that it is possible with out system to accurately measure sympathetic nerve activity in the awake rat, together with intra-arterial pressure and heart rate.

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