title: Modification by diltiazem, a calcium antagonist, of the pulmonary vagal and cardiac sympathetic chemoreflexes in the dog.
abstract: 1. Experiments were performed on anaesthetized, open-chest dogs to determine the effects of diltiazem on: the pulmonary vagal chemoreflex evoked by intravenous (i.v.) injection of capsaicin; cardiac sympathetic chemoreflexes activated by epicardial application of bradykinin or capsaicin; and baroreflex-mediated changes in heart rate resulting from both pressor and depressor effects produced by i.v. injections of noradrenaline and bradykinin, respectively. 2. Diltiazem infused i.v. at a rate of 10-30 micrograms/kg per min (mean cumulative dose 0.53 +/- 0.05 mg/kg, n = 9), did not affect basal heart rate, despite significant (P less than 0.001) reduction of resting blood pressure. 3. Diltiazem treatment did not affect the pressor responses to i.v. noradrenaline (0.3 micrograms/kg) or the hypotensive effects of i.v. bradykinin (0.3 micrograms/kg), but reduced significantly both the baroreflex-mediated bradycardia (P less than 0.01) and tachycardia (P less than 0.05) occurring with noradrenaline and bradykinin, respectively. 4. In contrast, diltiazem greatly enhanced reflex bradycardia (P less than 0.001) and systemic hypotension (P less than 0.01) resulting from activation of the afferent vagal pulmonary receptors by i.v. capsaicin (3-5 micrograms/kg). 5. Reflex pressor responses evoked by activation of the afferent cardiac sympathetic neurons by epicardial application of bradykinin (1 microgram) or capsaicin (10-20 micrograms) were not affected by diltiazem, but the corresponding reflex increases in heart rate evoked by both substances were significantly (P less than 0.01) reduced. 6. The results indicate that diltiazem, while reducing the influence of sinoaortic baroreceptors on heart rate, facilitates the reflex vagal control of the cardiac pacemaker by the afferent cardiopulmonary vagal receptors. These nervous reflex mechanisms, which include attenuation of positive chronotrophic effects that may result from ischaemia-induced activation of the afferent cardiac sympathetic neurons, may play an important role in the protective action of diltiazem in ischaemic heart disease.
authors: Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia.
authors: J
authors: J
authors: Staszewska-Woolley
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D002628:Chemoreceptor Cells / Q000187:drug effects*; D004110:Diltiazem / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D006321:Heart / Q000294:innervation; D006339:Heart Rate / Q000187:drug effects; D008168:Lung / Q000294:innervation; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D011311:Pressoreceptors / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000187:drug effects*; D014630:Vagus Nerve / Q000187:drug effects*
chemical_list: D004110:Diltiazem; D002211:Capsaicin; D001920:Bradykinin; D009638:Norepinephrine