Inhibitory role of capsaicin-sensitive afferent neurons and nitric oxide in hemostasis.
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.
Lippe
I T
IT
Department of Experimental and Clinical Pharmacology, University of Graz, Austria.
Sametz
W
W
Sabin
K
K
Holzer
P
P
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001760:Bleeding Time; D001777:Blood Coagulation / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology*; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D006487:Hemostasis / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D009569:Nitric Oxide; D001120:Arginine; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin; D019331:NG-Nitroarginine Methyl Ester