N-domain angiotensin I-converting enzyme with 80 kDa as a possible genetic marker of hypertension.
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 urine: Wistar-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.
Marques
Georgia D M
GD
Departamento de Medicina, Disciplina de Nefrologia, UNIFESP, Escola Paulista de Medicina, INCOR, São Paulo, SP, Brazil.
Quinto
Beata M R
BM
Plavinik
Frida L
FL
Krieger
José E
JE
Marson
Odair
O
Casarini
Dulce E
DE
D000595:Amino Acid Sequence; D000818:Animals; D005819:Genetic Markers; D006973:Hypertension / Q000201:enzymology* / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D007703:Peptidyl-Dipeptidase A / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000652:urine*; D017434:Protein Structure, Tertiary; D051381:Rats; D011914:Rats, Inbred BN; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017208:Rats, Wistar; D016415:Sequence Alignment
D005819:Genetic Markers; D007703:Peptidyl-Dipeptidase A