In vivo effects of fenoldopam on autonomic nervous system after inhibition or activation of ganglionic transmission.
The study investigated the effects of dopamine D1-like receptor stimulation on the autonomic nervous system. Fenoldopam (20 microg/kg) was injected i.v. in conscious sinoaortic denervated dogs, that is, surgically deprived of baroreflex pathways. In barodenervated dogs, fenoldopam (20 microg/kg) induced arterial hypotension as well as bradycardia and reduced noradrenaline plasma levels. Pentolinium (0.1 mg/kg i.v.), used to induce partial blockade of nicotinic ganglionic receptors, suppressed the fenoldopam-induced decrease in sympathetic tone, suggesting a ganglionic location for the dopamine D1-like receptor. Moreover, the inability of fenoldopam to reduce the nicotine-induced increase in sympathetic tone suggests that a postsynaptic ganglionic location can be excluded for the dopamine D1-like receptor. The results of these "in vivo" experiments strongly suggest a presynaptic location for the ganglionic dopamine D1-like receptor, stimulation of which results in a reduction of sympathetic tone.
Vernejoul
Fabienne
F
Laboratoire de Pharmacologie Médicale et Clinique, INSERM U317, Faculté de Médecine, 37 allées Jules Guesde, 31073 Toulouse Cedex, France.
Damase-Michel
Christine
C
Montastruc
Jean-Louis
JL
Tran
Marie-Antoinette
MA
D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects* / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004285:Dogs; D018818:Fenoldopam / Q000494:pharmacology*; D005725:Ganglia, Autonomic / Q000187:drug effects* / Q000502:physiology; D005730:Ganglionic Blockers / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects* / Q000502:physiology; D009638:Norepinephrine / Q000097:blood; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000502:physiology
D005730:Ganglionic Blockers; D017447:Receptors, Dopamine D1; D018818:Fenoldopam; D009638:Norepinephrine