Mechanisms underlying the cardiovascular responses to peripheral administration of NPFF in the rat.
In the present study, we examined the possibility of the presence of the Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2 (NPFF) system in the rat heart as well as the effects of drugs affecting noradrenergic transmission upon the cardiovascular responses elicited by peripheral administration of NPFF. The presence of NPFF receptors on heart sections and of NPFF-immunoreactivity in heart tissue was demonstrated with autoradiographic and radioimmunoassay procedures, respectively. Intravenous administration of NPFF (100-300 micrograms/kg) produced a dose-dependent increase in blood pressure and heart rate without affecting plasma noradrenaline and adrenaline levels. These effects of NPFF were also observed, although attenuated, in catecholamine-depleted rats and in rats pretreated with a ganglionic blocking agent, hexamethonium (10 mg/kg, i.v.). Prazosin (100 micrograms/kg, i.v.), an alpha1 adrenergic receptor antagonist, reduced the NPFF-induced blood pressure response by 50%. In contrast, propranolol (2 mg/kg, i.v.) and metroprolol (0.5 mg/kg, i.v.), beta- and beta1 adrenergic receptor antagonists, respectively, reduced the NPFF-induced heart rate response by 50%. Surprisingly, the alpha2 adrenergic receptor antagonists, idazoxan (2 mg/kg, i.v.) and yohimbine (2 mg/kg, i.v.), both produced a drastic increase in the NPFF-induced heart rate response. These data, which demonstrate the presence of the NPFF system in the rat heart, suggest that the cardiovascular responses of peripheral administration of NPFF are mediated by the stimulation of peripheral NPFF receptors. In addition, the present data show that the aforementioned NPFF-induced responses are also mediated by catecholamine-dependent mechanisms and suggest a functional interaction between adrenergic and NPFF systems.
Allard
M
M
Institut National de la Santé et de la Recherche Médicale (INSERM) U.378, Université de Bordeaux II, France.
Labrouche
S
S
Nosjean
A
A
Laguzzi
R
R
D000595:Amino Acid Sequence; D000818:Animals; D002319:Cardiovascular System / Q000187:drug effects*; D002395:Catecholamines / Q000494:pharmacology; D005724:Ganglia / Q000187:drug effects / Q000378:metabolism; D007262:Infusions, Intravenous; D008297:Male; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000008:administration & dosage / Q000494:pharmacology*; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology*; D011311:Pressoreceptors / Q000187:drug effects; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects
D002395:Catecholamines; D009479:Neuropeptides; D009842:Oligopeptides; C053651:phenylalanyl-leucyl-phenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide