ABSTRACT
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. METHODS AND 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.
Subject(s)
Black People , Endothelins/biosynthesis , Endothelins/physiology , Hypertension/metabolism , Saphenous Vein/chemistry , Saphenous Vein/metabolism , Aged , Aspartic Acid Endopeptidases/biosynthesis , Aspartic Acid Endopeptidases/blood , Aspartic Acid Endopeptidases/metabolism , Coronary Artery Bypass , Endothelin-Converting Enzymes , Endothelins/blood , Endothelium, Vascular/chemistry , Endothelium, Vascular/cytology , Endothelium, Vascular/metabolism , Endothelium, Vascular/surgery , Female , Humans , Hypertension/blood , Male , Metalloendopeptidases/biosynthesis , Metalloendopeptidases/blood , Metalloendopeptidases/metabolism , Middle Aged , Protein Precursors/biosynthesis , Protein Precursors/blood , Protein Precursors/physiology , RNA, Messenger/biosynthesis , RNA, Messenger/blood , Receptor, Endothelin A , Receptor, Endothelin B , Receptors, Endothelin/biosynthesis , Saphenous Vein/cytology , Saphenous Vein/surgery , Up-Regulation/physiology , White PeopleABSTRACT
The purpose of this study was to investigate whether there are differences in the expression of the endothelin (ET) system in the peripheral vasculature of diabetic African-American (AA) and Caucasian (CA) patients. Tibial artery specimens were obtained from diabetic (MD = 8 and CAD = 5) and non-diabetic (AAND = 6 and CAND = 5) patients undergoing lower limb amputation. The gene expression of ET-1 precursor (PPET-1), ET(A)R and ET(B)R was determined by a reverse transcriptase polymerase chain reaction technique. PPET-1 and ET(A)R expression was up-regulated 4- and 3-fold, respectively, in both AA and CA diabetics (P<.05 vs non-diabetics). ET(B)R mRNA was significantly lower in AA diabetic patients. Function of ET-1 and ET receptors was assessed by vascular contractility assays. Vascular relaxation in response to sodium nitroprusside in arteries precontracted with ET-1 was significantly lower in AA (58% +/- 9) as compared to CA diabetics (74% +/- 5) (P<.05). In conclusion, this study demonstrated that the ET system is altered in favor of the contractile phenotype in AA diabetics and may contribute to the increased incidence of vascular complications in this population.