1. ¹School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia
2. ²Department of Pharmacology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia
3. ³Department of Physiology, Aras Windle, University College Cork, Cork, Ireland

Correspondence: Professor EJ Johns, Department of Physiology, Aras Windle, University College Cork, College Road, Cork, Ireland. E-mail: e.j.johns@ucc.ie

Received 19 November 2007; Revised 7 December 2007; Accepted 4 January 2008; Published online 11 February 2008.

Abstract

Background and purpose: This study investigated whether the ₁-adrenoceptor responsiveness of the renal vasculature was altered in the state of hypertension combined with renal failure.

Experimental approach: Male spontaneously hypertensive rats (SHR) received cisplatin (5 mg kg^-1 i.p.) to induce renal failure. Seven days later, the rats were anaesthetized and the reductions in renal blood flow (RBF) to electrical renal nerve stimulation (RNS) and intrarenal administration of three adrenoceptor agonists (noradrenaline, phenylephrine and methoxamine) were determined before and after amlodipine, 5-methylurapidil, chloroethylclonidine or BMY 7378.

Key results: In renal failure SHR (RFSHR), RBF and creatinine clearance were significantly reduced (approximately 70%), while urine output and fractional sodium excretion were four and twenty-fold higher, respectively, compared to SHR. Vasoconstrictions induced by RNS or the adrenoceptor agonists were greater in RFSHR than SHR, and these responses were blunted by 5-methylurapidil, BMY 7378 and amlodipine in the SHR, while chloroethylclonidine had no effect. In the RFSHR, all renal vasoconstrictions were reduced by amlodipine and BMY 7378 but 5-methylurapidil attenuated those caused by RNS, noradrenaline and methoxamine while those to phenylephrine were enhanced. Chloroethylclonidine potentiated renal vasoconstrictor responses to methoxamine and phenylephrine but not RNS or noradrenaline in RFSHR.

Conclusions and implications: These findings suggest _1A- and _1D-adrenoceptors mediated the renal vasoconstrictor responses in SHR and RFSHR. In the RFSHR, other ₁-adrenoceptor subtypes, for example, _1B-adrenoceptors appeared to play a greater role.