Saphenous vein endothelin system expression and activity in African American patients.
OBJECTIVE
Plasma endothelin (ET)-1 levels are significantly higher in African American hypertensive patients than in white hypertensive patients. However, whether the molecular components of vascular ET-1 biosynthesis and function are altered in this population remains to be established. Accordingly, the overall goal of this study was to investigate the effects of race on vascular mRNA and protein levels of ET-converting enzyme (ECE)-1 subisoforms, ET-1, and ET receptor profiles in hypertension.


RESULTS
Saphenous vein samples were obtained from African American (n=13) and white (n=15) patients undergoing coronary artery grafting surgery. The expression of preproET-1 and of ECE-1a was upregulated approximately 2- and 3-fold, respectively, in African Americans. In endothelium-intact vessels, the ET(A) expression was higher in whites. In endothelium-denuded vessels, the ET(B) mRNA was 3-fold higher in African Americans, suggesting that vasoconstriction-promoting ET(B) receptors are upregulated in this population. Vascular tissue ET-1 levels and ECE-1 activity were also augmented in African American patients.


CONCLUSIONS
This study demonstrated that the biosynthetic pathway of ET-1 is activated to a higher degree and that the ET(B) receptor subtype expression is altered in the peripheral vasculature of African American hypertensive patients. The augmented synthesis and altered expression of ET(B) receptors may both contribute to the increased incidence of hypertension and related complications in this patient population.
Department of Surgery, Medical University of South Carolina, Charleston, USA.
Ashley L
AL
Grubbs
Mark P
MP
Anstadt
Adviye
A
Ergul
D000368:Aged; D016282:Aspartic Acid Endopeptidases / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism; D044383:Black People; D001026:Coronary Artery Bypass; D000072396:Endothelin-Converting Enzymes; D016232:Endothelins / Q000096:biosynthesis* / Q000097:blood / Q000502:physiology*; D004730:Endothelium, Vascular / Q000737:chemistry / Q000166:cytology / Q000378:metabolism / Q000601:surgery; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000378:metabolism*; D008297:Male; D008666:Metalloendopeptidases / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism; D008875:Middle Aged; D011498:Protein Precursors / Q000096:biosynthesis / Q000097:blood / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000097:blood; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000096:biosynthesis; D012501:Saphenous Vein / Q000737:chemistry* / Q000166:cytology / Q000378:metabolism* / Q000601:surgery; D015854:Up-Regulation / Q000502:physiology; D044465:White People; D001741:Black or African American
D016232:Endothelins; D011498:Protein Precursors; D012333:RNA, Messenger; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; C000606923:ECE1 protein, human; D000072396:Endothelin-Converting Enzymes