Vascular α1-adrenergic sensitivity is enhanced in chronic kidney disease

Abstract

Chronic kidney disease (CKD) is often complicated by difficult-to-control hypertension, in part due to chronic overactivation of the sympathetic nervous system (SNS). CKD patients also exhibit a greater increase in arterial blood pressure for a given increase in sympathetic nerve activation, suggesting an augmented vasoconstrictive response to SNS activation (i.e., neurovascular transduction). One potential mechanism of increased sympathetic neurovascular transduction is heightened sensitivity of the vascular α₁-adrenergic receptors (α₁ARs), the major effectors of vasoconstriction in response to norepinephrine release at the sympathetic nerve terminals. Therefore, we hypothesized that patients with CKD have increased vascular α₁AR sensitivity. We studied 32 patients with CKD stages III and IV (age 59.9 ± 1.3 yr) and 19 age-matched controls (CON, age 63.2 ± 1.6 yr). Using a linear variable differential transformer (LVDT), we measured change in venoconstriction in response to exponentially increasing doses of the selective α₁AR agonist phenylephrine (PE) administered sequentially into a dorsal hand vein. Individual semilogarithmic PE dose-response curves were constructed for each participant to determine the PE dose at which 50% of maximum venoconstriction occurred (ED₅₀), reflecting α₁AR sensitivity. In support of our hypothesis, CKD patients had a lower PE ED₅₀ than CON (CKD = 2.23 ± 0.11 vs. CON = 2.63 ± 0.20, P = 0.023), demonstrating increased vascular α₁AR sensitivity. Additionally, CKD patients had a greater venoconstrictive capacity to PE than CON (P = 0.015). Augmented α₁AR sensitivity may contribute mechanistically to enhanced neurovascular transduction in CKD and may explain, in part, the greater blood pressure reactivity exhibited in these patients.

Keywords: dorsal hand vein technique; linear variable differential transformer; neural control of circulation; renal disease; vascular reactivity.

Fig. 1.

Representative dose-response curves plotting percent constriction as a function of phenylephrine (PE) dose for control (CON; left) and chronic kidney disease (CKD; right) participants.

Fig. 2.

Mean log ED₅₀ values between groups. CON, control. CKD, chronic kidney disease; n = 19 CON (14 M/5 F) and 32 CKD (27 M/5 F). Mean log ED₅₀ values were compared via unpaired, 2-tailed t-tests. *P = 0.023.