Long-term effect on blood pressure of early brief treatment by different antihypertensive agents: a study in the prague hypertensive rat.

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.