Involvement of muscarinic M1 receptor in the central pathway of the serotonin-induced Bezold-Jarisch reflex in rats.
The involvement of central muscarinic receptors in mediating the Bezold-Jarisch reflex elicited by injection of 5-hydroxytryptamine (5-HT) was studied in urethane/chloralose-anesthetized rats. Intravenous bolus injection of 5-HT (3.1 to 50 micrograms/kg) evoked a short-lasting dose-related bradycardia and hypotension, the Bezold-Jarisch reflex, accompanied with bursts of the efferent cervical vagus nerve. Systemic administration of atropine (0.1 and 1 mg/kg) blocked not only the cardiac responses but also the efferent cervical vagus nerve activity changes. Although the afferent cervical vagus nerve was also activated by an intravenous bolus injection of 5-HT, these responses were not altered by the systemic administration of even a high dose of atropine (1 mg/kg). Intracerebroventricular (i.c.v.) administration of pirenzepine (1 and 10 micrograms/10 microliters), a selective M1 receptor antagonist, caused a rightward shift of the 5-HT dose-response curve for efferent vagus nerve activity. In contrast, i.c.v. administration of muscarinic type 2 receptor antagonist, gallamine, and type 3 receptor antagonist, p-fluorohexahydrosiladifenidol, failed to alter the response in nerve activity to 5-HT. These results suggest that the activation of central nervous muscarinic receptors might be involved in mediating the Bezold-Jarisch reflex and that the subtype might belong to type 1.
Department of Cardiovascular Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
K
K
Saito
M
M
Yoshioka
T
T
Kohya
A
A
Kitabatake
D000818:Animals; D001285:Atropine / Q000008:administration & dosage / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D007276:Injections, Intraventricular; D008297:Male; D018727:Muscarinic Antagonists; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D009476:Neurons, Efferent / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000502:physiology*; D012018:Reflex / Q000187:drug effects*; D012701:Serotonin / Q000494:pharmacology*; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology
D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D012701:Serotonin; D001285:Atropine