Functional subtypes of renal alpha1-adrenoceptor in spontaneously hypertensive rats with streptozotocin-induced experimental diabetic nephropathy.

AIM: This study investigated the impact of hypertension combined with diabetic nephropathy on rat renal alpha(1)-adrenoceptor subtype composition.
METHODS: In streptozotocin-induced diabetic spontaneously hypertensive rats (SHR), diabetic nephropathy developed as reflected by increased kidney index, plasma creatinine, albumin excretion, creatinine clearance and fractional excretion of Na(+) (all p < 0.05). Renal vasoconstrictions caused by electrical stimulation of renal nerves and intrarenally administered noradrenaline (alpha-adrenoceptor agonist), phenylephrine (alpha(1)-adrenoceptor agonist) and methoxamine (alpha(1A)-adrenoceptor agonist) were determined in the presence and absence of intrarenally administered amlodipine (Ca(2+) channel blocker), 5-methylurapidil (alpha(1A)-adrenoceptor antagonist), chloroethylclonidine (alpha(1B)-adrenoceptor antagonist) and BMY 7378 (alpha(1D)-adrenoceptor antagonist).
RESULTS: In diabetic nephropathy SHR, there was a significant (all p < 0.05) attenuation of all adrenergically induced vasoconstrictor responses in the antagonists, except chloroethylclonidine, which caused a significant (all p < 0.05) enhancement of the responses.
CONCLUSION: The data demonstrated that there was a functional coexistence of alpha(1A)- and alpha(1D)-adrenoceptors in the renal vasculature of SHR irrespective of the presence of diabetic nephropathy. However, there was a minor contribution of pre-synaptic alpha-adrenoceptors to the adrenergically mediated vasoconstrictor responses in the diabetic nephropathy SHR. Copyright 2009 S. Karger AG, Basel.