Influence of combined hypertension and renal failure on functional alpha(1)-adrenoceptor subtypes in the rat kidney.
OBJECTIVE
This study investigated whether the alpha(1)-adrenoceptor responsiveness of the renal vasculature was altered in the state of hypertension combined with renal failure.


METHODS
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.


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
These findings suggest alpha(1A)- and alpha(1D)-adrenoceptors mediated the renal vasoconstrictor responses in SHR and RFSHR. In the RFSHR, other alpha(1)-adrenoceptor subtypes, for example, alpha(1B)-adrenoceptors appeared to play a greater role.
Hye Khan
M A
MA
School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia.
Sattar
M A
MA
Abdullah
N A
NA
Johns
E J
EJ
D000818:Animals; D004195:Disease Models, Animal; D006973:Hypertension / Q000150:complications / Q000503:physiopathology*; D007668:Kidney / Q000098:blood supply / Q000503:physiopathology; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000378:metabolism*; D051437:Renal Insufficiency / Q000150:complications / Q000503:physiopathology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
C547715:Adra1a protein, rat; C547718:Adra1b protein, rat; C547721:Adra1d protein, rat; D018340:Receptors, Adrenergic, alpha-1