Inhibitory role of capsaicin-sensitive afferent neurons and nitric oxide in hemostasis

1993 ◽  
Vol 265 (6) ◽  
pp. H1864-H1868 ◽  
Author(s):  
I. T. Lippe ◽  
W. Sametz ◽  
K. Sabin ◽  
P. Holzer
Keyword(s):  
Nitric Oxide ◽  
Platelet Aggregation ◽  
Bleeding Time ◽  
Antithrombin Iii ◽  
Mesenteric Arteries ◽  
Thrombin Time ◽  
Afferent Neurons ◽  
No Formation ◽  
Inhibitory Role

Capsaicin-sensitive afferent neurons control blood flow via release of peptide transmitters and formation of nitric oxide (NO). The present study examined whether capsaicin-sensitive afferent neurons and NO interact in the control of hemostasis. Afferent nerve ablation by pretreating rats with a neurotoxic dose of capsaicin (125 mg/kg) led to a 26% reduction of the time of bleeding from punctured small mesenteric arteries in pentobarbital-anesthetized animals. Blockade of NO formation by NG-nitro-L-arginine methyl ester (L-NAME; 10 mg/kg) attenuated the bleeding time in capsaicin-pretreated rats but had no effect in vehicle-pretreated rats. Platelet aggregation induced by ADP was significantly augmented by 12% in capsaicin-pretreated rats. L-NAME did not alter platelet aggregation in vehicle-pretreated rats but enhanced it in capsaicin-pretreated animals. The prothrombin and partial thromboplastin time and the plasma levels of fibrinogen and antithrombin III remained unchanged by capsaicin or L-NAME, whereas the thrombin time was reduced in capsaicin-pretreated rats. These data indicate that capsaicin-sensitive afferent neurons play an inhibitory role in platelet aggregation and hemostasis, a function in which they interact with the NO system.

Prolonged bleeding time in experimental cirrhosis: role of nitric oxide

1999 ◽  
Vol 30 (3) ◽  
pp. 456-460 ◽  
Author(s):  
Liliana Albornoz ◽  
Juan Carlos Bandi ◽  
Juan Carlos Otaso ◽  
Oscar Laudanno ◽  
Ricardo Mastai
Keyword(s):  
Nitric Oxide ◽  
Bleeding Time ◽  
Experimental Cirrhosis ◽  
Prolonged Bleeding ◽  
Prolonged Bleeding Time

scholarly journals Nitric oxide synthase-mediated blood pressure regulation in obese melanocortin-4 receptor-deficient pregnant rats

2016 ◽  
Vol 311 (5) ◽  
pp. R851-R857 ◽  
Author(s):  
Frank T. Spradley ◽  
Jennifer M. Sasser ◽  
Jacqueline B. Musall ◽  
Jennifer C. Sullivan ◽  
Joey P. Granger
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Mesenteric Arteries ◽  
Elevated Blood Pressure ◽  
Pressure Regulation ◽  
Elevated Blood ◽  
Pregnant Rats ◽  
Melanocortin 4 Receptor ◽  
Regulation Of Blood Pressure

Although obesity increases the risk for hypertension in pregnancy, the mechanisms responsible are unknown. Increased nitric oxide (NO) production results in vasodilation and reduced blood pressure during normal pregnancy in lean rats; however, the role of NO is less clear during obese pregnancies. We examined the impact of obesity on NO synthase (NOS)-mediated regulation of blood pressure during pregnancy by testing the hypothesis that NOS activity, expression, and regulation of vascular tone and blood pressure are reduced in obese pregnant rats. At gestational day 19, melanocortin-4 receptor (MC4R)-deficient obese rats (MC4R) had greater body weight and fat mass with elevated blood pressure and circulating sFlt-1 levels compared with MC4R pregnant rats. MC4R pregnant rats also had less circulating cGMP levels and reduced total NOS enzymatic activity and expression in mesenteric arteries. Despite decreased biochemical measures of NO/NOS in MC4R rats, NOS inhibition enhanced vasoconstriction only in mesenteric arteries from MC4R rats, suggesting greater NOS-mediated tone. To examine the role of NOS on blood pressure regulation in obese pregnant rats, MC4R and MC4R pregnant rats were administered the nonselective NOS inhibitor NG-nitro-l-arginine methyl ester (l-NAME, 100 mg/l) from gestational day 14 to 19 in drinking water. The degree by which l-NAME raised blood pressure was similar between obese and lean pregnant rats. Although MC4R obese pregnant rats had elevated blood pressure associated with reduced total NOS activity and expression, they had enhanced NOS-mediated attenuation of vasoconstriction, with no evidence of alterations in NOS-mediated regulation of blood pressure.

scholarly journals Role of NO in arterial vascular function of intertidal fish (Girella laevifrons) and marine fish (Isacia conceptionis)

2016 ◽  
Vol 76 (2) ◽  
pp. 500-505
Author(s):  
F. A. Moraga ◽  
N. Urriola-Urriola
Keyword(s):  
Nitric Oxide ◽  
Sodium Nitroprusside ◽  
Marine Fish ◽  
Vascular Function ◽  
Isometric Tension ◽  
Mesenteric Arteries ◽  
Response Curves ◽  
Intertidal Fish ◽  
Branchial Arteries

Abstract Previous studies performed in intertidal fish (Girella laevifrons),as well as marine fish (Isacia conceptionis), showed that acetylcholine (ACh) produced contractions mediated by cyclooxygenases that were dependent on the area and potency of contraction in several arterial vessels. Given that the role of nitric oxide is poorly understood in fish, the objective of our study was to evaluate the role of nitric oxide in branchial afferent (ABA), branchial efferent (ABE), dorsal (DA) and mesenteric (MA) arterial vessels from both Girella laevifrons and Isacia conceptionis. We studied afferent and efferent branchial, dorsal and mesenteric arteries that were dissected from 6 juvenile specimens. Isometric tension studies were done using dose response curves (DRC) for Ach (10–13 to 10–3 M) and blockade with L-NAME (10–5 M), and DRC for sodium nitroprusside (SNP, a donor of NO). L-NAME produced an attenuation of the contractile response in the dorsal, afferent and efferent branchial arteries and a potentiation of the contraction in the MA. SNP caused 70% dilation in the mesenteric artery and 40% in the dorsal artery. Our results suggest that Ach promotes precarious dilatation in MA mediated by NO; data that is supported by the use of sodium nitroprusside. In contrast, in the vessels DA, ABA and EBA our results support that the pathway Ach-NO-relaxation is absent in both species.

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 Megakaryocyte-restricted MYH9 inactivation dramatically affects hemostasis while preserving platelet aggregation and secretion

Blood ◽  
2007 ◽  
Vol 110 (9) ◽  
pp. 3183-3191 ◽  
Author(s):  
Catherine Léon ◽  
Anita Eckly ◽  
Béatrice Hechler ◽  
Boris Aleil ◽  
Monique Freund ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Bleeding Time ◽  
Strong Increase ◽  
Clot Retraction ◽  
Gene Encoding ◽  
Normal Platelet ◽  
Coated Surface ◽  
Platelet Functions

Abstract Mutations in the MYH9 gene encoding the nonmuscle myosin heavy chain IIA result in bleeding disorders characterized by a macrothrombocytopenia. To understand the role of myosin in normal platelet functions and in pathology, we generated mice with disruption of MYH9 in megakaryocytes. MYH9Δ mice displayed macrothrombocytopenia with a strong increase in bleeding time and absence of clot retraction. However, platelet aggregation and secretion in response to any agonist were near normal despite absence of initial platelet contraction. By contrast, integrin outside-in signaling was impaired, as observed by a decrease in integrin β3 phosphorylation and PtdIns(3,4)P2 accumulation following stimulation. Upon adhesion on a fibrinogen-coated surface, MYH9Δ platelets were still able to extend lamellipodia but without stress fiber–like formation. As a consequence, thrombus growth and organization, investigated under flow by perfusing whole blood over collagen, were strongly impaired. Thrombus stability was also decreased in vivo in a model of FeCl3-induced injury of carotid arteries. Overall, these results demonstrate that while myosin seems dispensable for aggregation and secretion in suspension, it plays a key role in platelet contractile phenomena and outside-in signaling. These roles of myosin in platelet functions, in addition to thrombocytopenia, account for the strong hemostatic defects observed in MYH9Δ mice.

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