Presence of presynaptic inhibitory alpha 1-adrenoceptors in the cardiac sympathetic nerves of the dog: effects of prazosin and yohimbine on sympathetic neurotransmission to the heart.
The effects of prazosin and yohimbine on sympathetic neurotransmission to the heart were investigated in perfused dog hearts in situ in an attempt to determine whether alpha 1-adrenoceptors are located presynaptically in the cardiac sympathetic nerves. Intra-arterial injections of prazosin (1-30 micrograms) and yohimbine (0.3-10 micrograms) into the right coronary artery during cardiac sympathetic nerve stimulation further increased the tachycardia resulting from the stimulation. Continuous infusions of methoxamine (20-40 micrograms/min) and of clonidine (2-4 micrograms/min) into the right coronary artery during cardiac sympathetic nerve stimulation caused sustained reduction of the tachycardia. Prazosin under methoxamine infusion enhanced the tachycardia to a greater extent than in the absence of methoxamine. Prazosin under clonidine infusion enhanced the tachycardia to the same extent as it did in the absence of clonidine. These results suggest that prazosin antagonizes the effect of methoxamine but does not antagonize that of clonidine. The results obtained with yohimbine were in contrast to the effects of prazosin, showing the antagonism of clonidine by yohimbine. Prazosin and yohimbine both had little effect on the heart rate during either the resting state or the infusion of norepinephrine. These results suggest that the prazosin- and yohimbine-induced enhancement of the tachycardia resulting from cardiac sympathetic nerve stimulation is due to a presynaptic effect. However, the presynaptic effect of prazosin appears to differ from that of yohimbine. The presence of presynaptic alpha 1-adrenoceptors regulating norepinephrine release, as well as of alpha 2-adrenoceptors, is suggested in the cardiac sympathetic nerves of the dog.
D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D004285:Dogs; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology*; D011799:Quinazolines / Q000494:pharmacology*; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D013233:Stellate Ganglion / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects*; D013610:Tachycardia / Q000139:chemically induced; D015016:Yohimbine / Q000494:pharmacology*
D011799:Quinazolines; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D008729:Methoxamine; D003000:Clonidine; D009638:Norepinephrine; D011224:Prazosin