Faculty Collaboration Database

Influence of cisplatin-induced renal failure on the alpha(1)-adrenoceptor subtype causing vasoconstriction in the kidney of the rat. Eur J Pharmacol 2007 Aug 13;569(1-2):110-8

Date

06/15/2007

Pubmed ID

17559832

DOI

10.1016/j.ejphar.2007.04.063

Scopus ID

2-s2.0-34547459679 (requires institutional sign-in at Scopus site)   40 Citations

Abstract

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.

Author List

Khan AH, Sattar MA, Abdullah NA, Johns EJ

MESH terms used to index this publication - Major topics in bold

Amlodipine
Animals
Cisplatin
Clonidine
Dose-Response Relationship, Drug
Electric Stimulation
Injections, Intraperitoneal
Kidney
Male
Methoxamine
Norepinephrine
Phenylephrine
Piperazines
Rats
Rats, Inbred WKY
Receptors, Adrenergic, alpha-1
Renal Circulation
Renal Insufficiency
Vasoconstriction
Vasodilator Agents