Long–Term Effect on Blood Pressure of Early Brief Treatment by Different Antihypertensive Agents: A Study in the Prague Hypertensive Rat

Abstract

In the Prague hypertensive rat (PHR), a strain of genetic hypertension derived from Wistar, administration of various antihypertensive drugs (AHD) during the developmental phase of hypertension (weeks 5–9 of life) prevents the rise of blood pressure. However, only drugs blocking the renin–angiotensin system (RAS, i.e. AT1–antagonist losartan and ACE inhibitor perindopril) have a long–term effect on blood pressure leading to values of systolic blood pressure (SBP) of 174.5±14.5 and 169.8±15.3 mmHg, respectively, at week 30. At this time, control, untreated PHR have a SBP of 222.0±16.6 mmHg (p<0.01 for both groups); age–matched PNR (Prague normotensive rat, bred in parallel with PHR from the same parent pair) exhibit values as low as 123.3±11.7 mmHg (p<0.01 from all other values). When losartan was administered to another group of PHR not only at weeks 5–9 but once more at weeks of 15–19 of age, the values of their SBP at week 30 were 156.8±12.64 mmHg, i.e., values significantly (p<0.01) different not only from 239.7±17.59 mmHg (value of the untreated PHR group) but also from 174.5±14.5 mmHg (value of PHR to which losartan was administered only once, at weeks 5–9). Thus, twice repeated administration of losartan in young age almost normalizes blood pressure deep into adult age. Proteinuria, a common finding in adult PHR, is also significantly lower in adult age in both groups receiving at weeks 5–9 drugs blocking RAS; the values at week 30 are 4.0±0.26 mg/24 h/rat in the losartan and 3.87±0.27 in the perindopril group, in contrast to 12.8±1.08 (p<0.01 for both groups) in control PHR. In conclusion, early brief administration (weeks 5–9 of life) of RAS–blocking agents to PHR led to long–term antihypertensive and antiproteinuric effects. These effects were significantly intensified by a second brief administration at weeks 15–19.