Abstract: FR-PO207

Patients with CKD Have Heightened Vascular α1-Adrenergic Receptor Sensitivity

Session Information

Category: Hypertension

  • 1103 Vascular Biology and Dysfunction

Authors

  • Morison, Doree Gardner, Emory University School of Medicine, Atlanta, Georgia, United States
  • Downey, Ryan M, Emory University School of Medicine, Atlanta, Georgia, United States
  • Dacosta, Dana, Emory University School of Medicine, Atlanta, Georgia, United States
  • Park, Jeanie, Emory University School of Medicine, Atlanta, Georgia, United States
Background

Patients with chronic kidney disease (CKD) have sympathetic overactivity and difficult-to-control hypertension. Our previous studies showed that CKD patients have augmented increases in blood pressure in response to the same degree of sympathetic nerve activation, suggesting heightened neurovascular transduction. We hypothesized that augmented vascular α1-adrenergic receptor (α1-AR) sensitivity contributes to the exaggerated vasoconstriction and blood pressure responses to sympathetic activation in CKD.

Methods

In 13 CKD (Stage IIIB and IV) patients and 5 Controls, we measured the degree of vasoconstriction of a dorsal hand vein in response to serial infusions of 10 doses (ranging 15-12,000 ng/min) of the selective α1-AR agonist phenylephrine (PE) using a linear variable differential transformer with a movable central core to detect changes in vascular diameter. Vascular diameters were expressed as a % reduction from baseline maximum dilation, and plotted against PE dose rates in individual semilogarithmic dose-response graphs, and analyzed using a 4-variable sigmoid dose-response model. The natural log (ln) PE dose that produced a 50% maximal constriction (ED50) reflects sensitivity to PE (i.e. α1-AR sensitivity).

Results

CKD patients had a significantly lower PE ED50 compared to Controls (ln PE dose 5.1±0.5 vs 8.3±0.9 ng/min, p=0.0045), demonstrating that CKD patients have heightened vasoconstriction in response to PE.

Conclusion

Augmented vascular α1-AR sensitivity could contribute to increased neurovascular transduction and hypertension in CKD patients.

Figure. Vascular α1-adrenergic receptor sensitivity is heightened in chronic kidney disease.

Funding

  • Other NIH Support