Renal neuroadrenergic hypertension upregulates α₂ adrenoceptors and downregulates at₁ receptors

Renal vascular sensitivity to norepinephrine and angiotensin II are enhanced following chronic renal neuroadrenergic hypertension in dogs. Hypertension was associated with sustained natriuresis and diuresis despite continued intrarenal neuroadrenergic stimulation. To address the mechanisms of increased renal vascular reactivity and renal neuroadrenergic natriuresis, we examined alterations in intrarenal adrenergic (α₁, α₂, β) and AT₁ receptors prior to and following chronic neuroadrenergic hypertension. Control and norepinephrine infused kidneys were divided into outer cortical, inner cortical, medullary, and vessel fractions. Competitive radioligand binding techniques and Scatchard analysis were employed to measure α₁, α₂ and total β adrenergic receptors in membrane protein from each kidney region with ³H-prazosin, ³H-rauwolscine, and ³H-CGP-12177, respectively. AT₁ receptors were quantitated in outer and inner cortical fractions with Western blot analysis. Maximal binding (B_max) of ³H-rauwolscine was increased in all fractions from norepinephrine infused kidneys relative to control whereas the B_max for ³H-Prazosin in norepinephrine infused kidneys was decreased in the vessel fraction compared to control kidneys. The B_max for ³H-CGP-12177 was similar in all fractions from norepinephrine infused and control kidneys. No changes in binding affinity were detected in norepinephrine infused kidneys when compared to controls. Western blot analysis revealed decreased AT₁ receptors in outer cortical and inner cortical fractions while AT₁ receptors in the vessel fraction tended to increase in norepinephrine infused kidneys relative to controls. Thus, increased vascular reactivity in vivo and in vitro were associated with increased renal α₂ adrenoceptors, whereas sustained increases in urinary sodium excretion were accompanied by reductions in cortical AT₁ receptors. We conclude that enhanced renal vascular and excretory responses in chronic renal neuroadrenergic hypertension may be mediated by reciprocal alterations in intrarenal vascular and tubular adrenergic and AT₁ receptors.