Probing the mechanisms of intradialytic hypertension: a pilot study targeting endothelial cell dysfunction.
OBJECTIVE
Intradialytic hypertension may be caused by an impaired endothelial cell response to hemodialysis. Carvedilol has been shown to improve endothelial cell function in vivo and to block endothelin-1 release in vitro. This study hypothesized that carvedilol would improve endothelial cell function and reduce the occurrence of intradialytic hypertension.


METHODS
A prospective 12-week pilot study of carvedilol titrated to 50 mg twice daily was performed among 25 hemodialysis participants with intradialytic hypertension. Each patient served as his or her own control. Paired tests were used to analyze changes in BP and endothelial cell function--assessed by flow-mediated vasodilation, endothelial progenitor cells (aldehyde dehydrogenase bright activity and CD34(+)CD133(+)), asymmetric dimethylarginine, and endothelin-1--from baseline to study end.


RESULTS
Flow-mediated vasodilation was significantly improved with carvedilol (from 1.03% to 1.40%, P=0.02). There was no significant change in endothelial progenitor cells, endothelin-1, or asymmetric dimethylarginine. Although prehemodialysis systolic BP was unchanged (144-146 mmHg, P=0.5), posthemodialysis systolic BP, 44-hour ambulatory systolic BP, and the frequency of intradialytic hypertension decreased with carvedilol (159-142 mmHg, P<0.001; 155-148 mmHg, P=0.05; and 77% [4.6 of 6] to 28% [1.7 of 6], P<0.001, respectively).


CONCLUSIONS
Among hemodialysis participants with intradialytic hypertension, targeting endothelial cell dysfunction with carvedilol was associated with modest improvements in endothelial function, improved intradialytic and interdialytic BP, and reduced frequency of intradialytic hypertension. Randomized controlled trials are required to confirm these findings.
University of Texas Southwestern Medical Center, Dallas, Texas 75390-8523, USA. inrig@utsouthwestern.edu
Jula K
JK
Inrig
Peter
P
Van Buren
Catherine
C
Kim
Wanpen
W
Vongpatanasin
Thomas J
TJ
Povsic
Robert
R
Toto
D000071916:AC133 Antigen; D000328:Adult; D000368:Aged; D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism; D018952:Antigens, CD34 / Q000378:metabolism; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D018660:Blood Pressure Monitoring, Ambulatory; D001835:Body Weight / Q000187:drug effects; D002227:Carbazoles / Q000009:adverse effects / Q000627:therapeutic use*; D000077261:Carvedilol; D019332:Endothelin-1 / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000378:metabolism; D010865:Pilot Projects; D011412:Propanolamines / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies; D006435:Renal Dialysis / Q000009:adverse effects*; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism; D013781:Texas; D013997:Time Factors; D016896:Treatment Outcome; D059289:Vascular Stiffness / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000009:adverse effects / Q000627:therapeutic use*
D000071916:AC133 Antigen; D015703:Antigens, CD; D018952:Antigens, CD34; D000959:Antihypertensive Agents; D015415:Biomarkers; D002227:Carbazoles; D019332:Endothelin-1; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; D011412:Propanolamines; D014665:Vasodilator Agents; D000077261:Carvedilol; C018524:N,N-dimethylarginine; D001120:Arginine; D000444:Aldehyde Dehydrogenase