Renal and cardiovascular role of the neuropeptide Y Y1 receptor in ischaemic heart failure rats.
The cardiovascular role of the neuropeptide Y Y1 receptors in-vivo and in-vitro in ischaemic heart failure was evaluated by using the novel neuropeptide Y Y1 selective antagonist BIBP 3226 (R-N2-(diphenylacetyl)-N-[(4-hydroxyphenyl)methyl]-D-arginine-amid e). In pithed rats, incremental doses of BIBP 3226 inhibited the exogenous neuropeptide Y induced pressor response in a dose-related fashion and a bolus injection of BIBP 3226 (0.5 mg kg(-1)) significantly shifted the pressor response curve of exogenous neuropeptide Y to the right. The potentiation effect to exogenous neuropeptide Y on the pressor response to preganglionic sympathetic nerve stimulation in ischaemic heart failure rats as well as on the contractile response to noradrenaline in renal arteries in sham-operated animals were also inhibited by the neuropeptide Y Y1 antagonist. In conscious ischaemic heart failure rats, incremental doses of BIBP 3226 (0.125-1 mg kg(-1)) significantly reduced basal blood pressure and heart rate. Compared with sham-operated rats, neuropeptide Y by itself induced no contraction and no potentiation on noradrenaline elicited contraction in renal artery of the ischaemic heart failure rat. Furthermore, under in-vivo conditions, BIBP 3226 did not influence basal renal function or the response to exogenous neuropeptide Y on urinary volume, urinary sodium and urinary potassium. Our results demonstrate that although there is a downregulation of the Y1 receptors by ischaemic heart failure, Y1 receptors are still mainly involved in cardiovascular actions of exogenous neuropeptide Y and play a role in maintaining basal blood pressure and heart rate in ischaemic heart failure. However, our data do not imply any significant role of Y1 receptors on basal renal function in the ischaemic heart failure rat model.
Zhao
X H
XH
Department of Clinical Pharmacology, Sahlgrenska University Hospital, Göteborg, Sweden.
Sun
X Y
XY
Bergdahl
A
A
Edvinsson
L
L
Hedner
T
T
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000503:physiopathology*; D003655:Decerebrate State / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D007668:Kidney / Q000503:physiopathology*; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology*; D009478:Neuropeptide Y / Q000494:pharmacology / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D017476:Receptors, Neuropeptide Y / Q000819:agonists / Q000037:antagonists & inhibitors / Q000187:drug effects*; D012077:Renal Artery / Q000187:drug effects; D012964:Sodium / Q000652:urine
C092926:BIBP 3226; D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; D001120:Arginine; D012964:Sodium; D011188:Potassium; D009638:Norepinephrine