Involvement of alpha 1-adrenoceptors in chronotropic responses to endogenously released amines in the pithed rat.
1. In pithed rats, yohimbine (1 mg/kg i.v.) enhanced the positive chronotropic responses to spinal stimulation of cardiac sympathetic nerves with eight pulses delivered at 2 or 4 Hz, indicating that auto-inhibition was operating, but did not increase responses to shorter lengths of trains of 8 pulses at 8, 16 or 32 Hz which did not allow sufficient time for auto-inhibition to come into effect. 2. The positive chronotropic response to cardiac sympathetic nerve stimulation with eight pulses at 8 Hz of about 60 beats/min was not affected by prazosin (1 mg/kg) or diltiazem (0.2 mg/kg), but was reduced to about 20% of the control value by propranolol (1 mg/kg). 3. In the presence of propranolol, the residual positive chronotropic responses to cardiac sympathetic nerve stimulation were virtually abolished by prazosin (1 mg/kg) or diltiazem (0.2 mg/kg). 4. The positive chronotropic response to tyramine (0.1 mg/kg i.v.) was reduced from 100 to 12 beats/min by propranolol (1 mg/kg), and the residual response was abolished by prazosin. 5. The findings indicate that noradrenaline released from cardiac sympathetic terminals by nerve stimulation or by tyramine acts on alpha 1-adrenoceptors to produce a positive chronotropic response that is revealed when beta-adrenoceptors are blocked.
De Luca
A
A
Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia.
Rand
M J
MJ
D000818:Animals; D001679:Biogenic Amines / Q000378:metabolism / Q000502:physiology*; D003655:Decerebrate State; D004110:Diltiazem / Q000494:pharmacology; D004347:Drug Interactions; D004558:Electric Stimulation; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D009411:Nerve Endings / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000187:drug effects; D014439:Tyramine / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D001679:Biogenic Amines; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D011433:Propranolol; D004110:Diltiazem; D009638:Norepinephrine; D014439:Tyramine; D011224:Prazosin