Stimulation of the renin angiotensin system (RAS) in an early stage of life causes sustained hypertension in rats

Abstract

Transient administration of inhibitors of the renin angiotensin system (RAS) during the prehypertensive period of spontaneously hypertensive rats leads to a long‐lasting lowering of blood pressure (BP) and a reduction of end organ damage. We tested if a transient stimulation of the RAS at young age would exert the opposite effect and permanently increases BP.Studies were performed in Cyp1a1 Ren2 transgenic rats. In this model the production of mouse renin is enhanced when 0.3% Indole‐3 carbinol (I3C) is added to the diet. After withdrawal of I3C the production of mouse renin stops almost immediately. Cyp1a1 Ren2 rats received I3C‐treatment between 4 to 8 weeks of age (WOA) or between 30–34 WOA. Non‐treated rats served as control. BP follow‐up was performed via tailcuff and intra‐arterial BP was determined at 4, 8, 12 and 20 WOA or 34 and 38 WOA. Data are presented as mean ± SEM.At 12 WOA, i.e. 4 weeks after I3C withdrawal, the I3C‐treated rats show a statistically significant increase in BP compared with control rats (156±18 versus 129±6 mmHg). This increase in BP is still present at 20 WOA, i.e. 12 weeks after I3C withdrawal (141±7 versus 125±6mmHg). In the adult rats (30–34 weeks), BP returned immediately to control values after stopping renin activation.This study shows that, at least in rats, sustained hypertension can be induced by a transient stimulation of the RAS in an early stage of life.