Influence of cisplatin-induced renal failure on the alpha(1)-adrenoceptor subtype causing vasoconstriction in the kidney of the rat.
This study investigated whether the alpha(1)-adrenoceptor subtype(s) mediating the vasoconstrictor actions of the renal sympathetic nerves were altered in rats with cisplatin-induced renal failure. Male Wistar Kyoto rats were used and half received cisplatin (5 mg/kg i.p.) to induce renal failure and were taken for study 7 days later. The renal blood flow reductions caused by electrical renal nerve stimulation and close intra-renal administration of noradrenaline, phenylephrine and methoxamine were determined before and after amlodopine (AMP), 5-methylurapidil (MeU), chloroethylclonidine (CEC) or BMY 7378. Water intake and creatinine clearance were decreased (P<0.05) by 40-50% while fractional excretion of sodium was increased two-fold in the cisplatin treated rats. Mean arterial pressure was higher, 110+/-2 versus 102+/-3 mmHg and renal blood flow was lower, 10.7+/-0.9 versus 18.9+/-0.1 ml/min/kg in the renal failure rats (both P<0.05). AMP, MeU and BMY 7378 decreased (all P<0.05) the adrenergically induced renal vasoconstrictor responses in the renal failure groups by 30 to 50% and in normal rats by 20 to 40%. In the presence of CEC, renal nerve stimulation and noradrenaline and methoxamine induced renal vasoconstrictor responses were enhanced (all P<0.05) in the renal failure but not in the normal rats. These data showed that alpha(1A)- and alpha(1D)-adrenoceptors were the major subtypes in mediating adrenergically induced renal vasoconstriction but there was no substantial shift in subtype in renal failure. The contribution of alpha(1B)-adrenoceptor subtypes either pre- or post-synaptic appeared to be raised in the renal failure rats.
Khan
Abdul H
AH
School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800 Penang, Malaysia.
Sattar
Munavvar A
MA
Abdullah
Nor A
NA
Johns
Edward J
EJ
D017311:Amlodipine / Q000494:pharmacology; D000818:Animals; D002945:Cisplatin / Q000008:administration & dosage / Q000633:toxicity*; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000098:blood supply / Q000294:innervation / Q000503:physiopathology*; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D011921:Rats, Inbred WKY; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D012079:Renal Circulation / Q000187:drug effects; D051437:Renal Insufficiency / Q000139:chemically induced / Q000503:physiopathology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
C547718:Adra1b protein, rat; D010879:Piperazines; D018340:Receptors, Adrenergic, alpha-1; D014665:Vasodilator Agents; C057446:5-methylurapidil; D017311:Amlodipine; D010656:Phenylephrine; C051731:chlorethylclonidine; D008729:Methoxamine; C053428:BMY 7378; D003000:Clonidine; D002945:Cisplatin; D009638:Norepinephrine