Differential regulation of vascular angiotensin I-converting enzyme in hypertension.
The angiotensin I-converting enzyme (ACE) gene is found on the locus that has been linked to high blood pressure after sodium loading in rats, so in the present study we investigated the role of vascular ACE for the pathophysiology of hypertension in the corresponding parental strains, Wistar-Kyoto (WKY) rats and stroke-prone spontaneously hypertensive rats (SHRSP), in basal conditions at different ages and after sodium loading. Blood pressure was already significantly enhanced in SHRSP from 4 weeks of age, and sodium loading induced an additional increase only in the hypertensive strain. In the aorta, basal ACE gene expression, analyzed by quantitative polymerase chain reaction, and ACE activity were similar in both strains, whereas mRNA levels were elevated in SHRSP after salt compared with WKY rats and correlated with an increase in enzymatic activity. In mesenteric arteries, ACE mRNA levels were significantly enhanced in SHRSP at all ages, although ACE activity was not different between the strains. These results were not modified after sodium loading. These data demonstrate that the level of ACE activity in plasma and vascular tissue can be controlled in a different manner within a rat strain and that in contrast to the soluble form, the membrane-bound ACE may be the one responsible for determining the vasoactive effects of angiotensin II. In addition, ACE undergoes a different regulation in vascular tissues of SHRSP compared with WKY rats, which might be involved in the regulation of blood pressure in these animals.
Fernández-Alfonso
M S
MS
Max Delbrück Centrum for Molecular Medicine, University Hospital Benjamin Franklin, Freie Universität, Berlin, Germany.
Kreutz
R
R
Zeh
K
K
Liu
Y
Y
Ganten
D
D
Paul
M
M
D000375:Aging / Q000502:physiology*; D000818:Animals; D001011:Aorta / Q000502:physiology*; D001483:Base Sequence; D001794:Blood Pressure; D004039:Diet, Sodium-Restricted; D004198:Disease Susceptibility; D015870:Gene Expression; D006973:Hypertension / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008638:Mesenteric Arteries / Q000502:physiology*; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D015335:Molecular Probes; D007703:Peptidyl-Dipeptidase A