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Augmented Vascular α 1 ‐Adrenergic Receptor Sensitivity in Humans with Chronic Kidney Disease
Author(s) -
Morison Doree Gardner,
Li Yunxiao,
Fonkoue Ida,
Kankam Melanie,
DaCosta Dana,
Rapista Derick,
Downey Ryan M.,
Park Jeanie
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.736.3
Subject(s) - vasoconstriction , medicine , phenylephrine , blood pressure , vasodilation , cardiology , endocrinology , agonist , anesthesia , receptor
Patients with chronic kidney disease (CKD) have sympathetic overactivity and difficult‐to‐control hypertension. CKD patients also have exercise‐induced hypertension contributing to poor physical capacity. Our previous studies showed that CKD patients have augmented increases in blood pressure in response to the same degree of sympathetic activation during exercise, suggesting heightened neurovascular transduction of sympathetic nerve activity. 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. In 28 CKD (Stage III and IV) patients and 11 matched 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 concentrations in individual semi‐logarithmic dose‐response curves, and analyzed using a 5‐variable sigmoid dose‐response model. The natural log (ln) PE dose that produced a 50% maximal constriction (ED50) was calculated to reflect sensitivity to PE (i.e. α1‐AR sensitivity). CKD patients had a significantly lower PE ED50 compared to Controls (ln PE dose 5.15±0.30 vs 6.68±0.64 ng/min, p=0.022), demonstrating that CKD patients have heightened vasoconstriction in response to vascular α1 AR activation. CKD patients also had a significantly greater change in systolic blood pressure (SBP) during rhythmic hand grip exercise performed at 20% of maximum voluntary contraction compared to Controls (SBP +20.18±2.7 vs +10.43±1.74 mmHg, p=0.01), suggesting that augmented vascular α1‐AR sensitivity may contribute to increased neurovascular transduction and heightened exercise pressor responses in CKD. There was also a trend towards a positive linear correlation between estimated glomerular filtration rate (eGFR) and PE ED50. Augmented vascular α1‐AR sensitivity may contribute to increased neurovascular transduction and hypertension in CKD patients . Support or Funding Information Supported by NIH HL‐098744, VA Merit I01CX001065, American Heart Association 15CSA24340001 This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .