Angiotensin-converting enzyme 2 (ACE2) and ACE activities display tissue-specific sensitivity to undernutrition-programmed hypertension in the adult rat.
Human epidemiological studies have shown that low birth weight is associated with hypertension in adulthood. Rodent models of intrauterine growth retardation (IUGR) support these findings because offspring from undernourished dams develop hypertension. Angiotensin-converting enzyme 2 (ACE2) is a newly described renin-angiotensin system (RAS) component that competes with ACE for angiotensin peptide hydrolysis and therefore may modulate blood pressure. However, ACE2 potential participation in hypertension programming remains unknown, although RAS alterations were reported in IUGR models. Hence, we first investigated the tissue distribution of ACE2 and ACE in the rat and then whether hypertension programming differentially affects both enzymes. Using multiplex RT-PCR and in situ hybridization, we show that ACE2 mRNA is widely expressed and coregionalized with ACE. Moreover, tissues involved in blood pressure homeostasis (lung, heart, and kidney) express high levels of both enzymes. Enzymatic assays reveal that ACE2 and ACE are coactive in these tissues. Adult (4-month-old) offspring from 70% food-restricted dams throughout gestation (FR30 rats) present mild hypertension, impaired renal morphology, as well as elevated plasma angiotensin II and aldosterone, suggesting alterations of the systemic RAS. In FR30 rats, we show that ACE2 and ACE activities are increased only in the lung, whereas their mRNA expression is not significantly altered, showing that the enzymes display tissue-specific sensitivity to programming. Our results indicate that ACE2 and ACE are coexpressed in numerous rat tissues and that their increased activity in the lung of FR30 rats may participate in hypertension programming.
Rivière
Guillaume
G
The UPRES-EA 2701, Laboratoire de Neuroendocrinologie du Développement, Université des Sciences et Technologies de Lille, 59655 Villeneuve d'Ascq Cedex, France.
Michaud
Annie
A
Breton
Christophe
C
VanCamp
Gilles
G
Laborie
Christine
C
Enache
Mihaela
M
Lesage
Jean
J
Deloof
Sylvie
S
Corvol
Pierre
P
Vieau
Didier
D
D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000097:blood; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000378:metabolism; D001794:Blood Pressure; D002268:Carboxypeptidases / Q000378:metabolism*; D003345:Corticosterone / Q000097:blood; D004198:Disease Susceptibility; D004573:Electrolytes / Q000652:urine; D005260:Female; D006973:Hypertension / Q000201:enzymology* / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000201:enzymology*; D008297:Male; D044342:Malnutrition / Q000097:blood / Q000150:complications*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood; D051381:Rats; D011921:Rats, Inbred WKY; D012083:Renin / Q000097:blood / Q000378:metabolism; D014018:Tissue Distribution
D004573:Electrolytes; D000804:Angiotensin II; D000450:Aldosterone; D002268:Carboxypeptidases; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2; D012083:Renin; D003345:Corticosterone