Vascular α1-adrenergic sensitivity is enhanced in chronic kidney disease

Justin D. Sprick, Doree L. Morison, C. Michael Stein, Yunxiao Li, Sachin Paranjape, Ida T. Fonkoue, Dana R. DaCosta, Jeanie Park

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)R485-R490
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume317
Issue number3
DOIs
StatePublished - Sep 2019
Externally publishedYes

Bibliographical note

Funding Information:
Research was supported by the National Heart Lung and Blood Institute Grant R01 HL-135183 (PI: J. Park) and the National Institute of Diabetes and Digestive and Kidney Diseases (T32DK007656, PI: J Sands); and the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Clinical Studies Center, Decatur, Georgia.

Publisher Copyright:
© 2019 American Physiological Society. All rights reserved.

Fingerprint

Dive into the research topics of 'Vascular α1-adrenergic sensitivity is enhanced in chronic kidney disease'. Together they form a unique fingerprint.

Cite this