Effect of dipyridamole on sympathetic nerve function: role of adenosine and presynaptic purinergic receptors.
The effect of dipyridamole on cardiac sympathetic neurotransmission was studied in pentobarbital-anesthetized dogs. Additional studies were performed to determine the involvement of adenosine and presynaptic purinergic receptors in the action of dipyridamole. Dipyridamole (2 mg/kg) produced significant impairment of the cardioacceleration observed during the stimulation of cardioaccelerator nerve, whereas the positive chronotropic effect of intravenous norepinephrine was not affected. This inhibitory effect of the compound could be antagonized by prior treatment of the animals with theophylline. Doses of adenosine (0.1 and 0.2 mg/kg/min) that did not have any effect on cardiac sympathetic nerve function in control animals caused significant impairment of the positive chronotropic effect of cardiac nerve stimulation in animals treated with a smaller dose of dipyridamole (0.5 mg/kg), which could also be antagonized by theophylline. The smaller dose of dipyridamole did not affect responses to cardiac nerve stimulation. Dipyridamole did not modify the effect of 2-chloroadenosine, an adenosine analog reported to be resistant to uptake and deamination, on sympathetic nerve function. A larger dose of 2-chloroadenosine, however, did produce inhibition of the positive chronotropic effect of cardiac nerve stimulation which could be antagonized by theophylline. These results demonstrate that dipyridamole can cause inhibition of sympathetic neurotransmission to the myocardium, and they further suggest that this action of the compound is mediated by endogenous adenosine acting on presynaptic purinergic receptors.
D000241:Adenosine / Q000502:physiology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004176:Dipyridamole / Q000494:pharmacology*; D004285:Dogs; D004357:Drug Synergism; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D011687:Purines / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000502:physiology*; D011955:Receptors, Drug / Q000502:physiology*; D011983:Receptors, Purinergic; D013564:Sympathetic Nervous System / Q000187:drug effects*; D013806:Theophylline / Q000494:pharmacology
D011687:Purines; D011956:Receptors, Cell Surface; D011955:Receptors, Drug; D011983:Receptors, Purinergic; D004176:Dipyridamole; D013806:Theophylline; D000241:Adenosine