Influence of cisplatin-induced renal failure on the α1-adrenoceptor subtype causing vasoconstriction in the kidney of the rat

This study investigated whether the α1-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 α1A- and α1D-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 α1B-adrenoceptor subtypes either pre- or post-synaptic appeared to be raised in the renal failure rats.