Central cardiovascular effects of rilmenidine and neuropeptide Y in the conscious spontaneously hypertensive rat: haemodynamic and biochemical evidence for a negative interaction.
The possible cardiovascular and biochemical interactions between the imidazoline ligand rilmenidine, a novel antihypertensive agent, and neuropeptide Y (NPY) were examined in spontaneously hypertensive rats (SHR). Rilmenidine (25-225 micrograms/kg) and NPY (1.7-15 micrograms/kg) both produced a significant, dose-dependent reduction in blood pressure (BP) after intracisternal (i.c.) administration in conscious SHR. When submaximal doses of rilmenidine (25 micrograms/kg) and NPY (1.7 micrograms/kg) were coadministered i.c., the resultant hypotension and bradycardia was less than either individual response and significantly less than the sum of their individual responses, suggesting the existence of an inhibitory interaction between these agents. To determine whether this interaction was evident at the second-messenger level, the effect of these agents on cyclic AMP levels was investigated in slices from the medulla oblongata of SHR. NPY (10(-6) and 10(-7) M) significantly inhibited forskolin-stimulated cyclic AMP production. Rilmenidine (10(-8)-10(-5) M) itself had no significant effect on forskolin-stimulated cyclic AMP levels in this system, but rilmenidine (10(-6) M) attenuated the inhibitory effect of NPY (10(-6) M) on cyclic AMP production. Thus, an inhibitory interaction between rilmenidine and NPY was observed at the hemodynamic and second-messenger level in the SHR.
McAuley
M A
MA
University of Glasgow, Department of Medicine and Therapeutics, Gardiner Institute, Scotland.
Reid
J L
JL
Macrae
I M
IM
D000262:Adenylyl Cyclases / Q000378:metabolism; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects*; D006973:Hypertension / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000378:metabolism; D009478:Neuropeptide Y / Q000494:pharmacology*; D010080:Oxazoles / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D000077769:Rilmenidine
D000316:Adrenergic alpha-Agonists; D009478:Neuropeptide Y; D010080:Oxazoles; D005576:Colforsin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D000077769:Rilmenidine