N-Domain Angiotensin I-Converting Enzyme With 80 kDa as a Possible Genetic Marker of Hypertension

• Published in: Hypertension (Dallas, Tex. 1979) Tex. 1979), 2003-10, Vol.42 (4, Part 2), p.693-701
• Main Authors: Marques, Georgia D.M., Quinto, Beata M.R., Plavinik, Frida L., Krieger, José E., Marson, Odair, Casarini, Dulce E.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Experimental diseases; Genetic Markers; Hypertension - enzymology; Hypertension - genetics; Male; Medical sciences; Molecular Sequence Data; Peptidyl-Dipeptidase A - chemistry; Peptidyl-Dipeptidase A - genetics; Peptidyl-Dipeptidase A - isolation & purification; Peptidyl-Dipeptidase A - urine; Protein Structure, Tertiary; Rats; Rats, Inbred BN; Rats, Inbred SHR; Rats, Inbred WKY; Rats, Wistar; Sequence Alignment
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/01.HYP.0000085784.18572.CB

ABSTRACT—We have previously described angiotensin I-converting enzyme (ACE) forms in urine of normotensive (190 and 65 kDa) and hypertensive patients (90 and 65 kDa, N-domain ACEs). Based on the results described above, experimental and genetic models of hypertension were investigated to distinguish hemodynamic and genetic influence on the generation of ACE profile in urineWistar-Kyoto and Brown Norway rats (WKY and BN), spontaneously and stroke-prone spontaneously hypertensive rats (SHR and SHR-SP), one kidney/one clip rats (1K1C), deoxycorticosterone acetate (DOCA) salt-treated and untreated rats, and enalapril-treated SHR (SHRen). Two peaks with ACE activity were separated from the urine of WKY and BN rats submitted to an AcA-44 column, WK-1/BN-1 (190 kDa), and WK-2/BN-2 (65 kDa), as described for urine of normotensive subjects. The same results were obtained for urine of 1K1C and DOCA salt-treated and untreated rats, analyzed to evaluate the influence of hemodynamic factors in the ACE profile in urine. The urine from SHR, SHR-SP, and SHRen presented 80 (S-1, SP-1, Sen-1) and 65 (S-2, SP-2, Sen-2) kDa ACE forms, differing from the urine profile of normotensive rats, but similar to that described for hypertensive patients. The presence of 80 kDa ACE in urine of SHR, SHR-SP, and SHRen and its absence in urine of experimental hypertensive rats (1K1C and DOCA salt) support the hypothesis that this enzyme could be a possible genetic marker of hypertension. Taken together, our results provide evidence that ACE forms with 90/80 kDa isolated from the urine of hypertensive subjects and genetic hypertensive animals behaves as a possible genetic marker of hypertension and not as a marker of high blood pressure.