Reduction of salt sensitivity in stroke-prone spontaneously hypertensive rats administered an AT1 receptor antagonist during suckling.
BACKGROUND
In this study, antihypertensive therapy was started during suckling and the effect on blood pressure (BP) and salt sensitivity of stroke-prone spontaneously hypertensive rats (SHRSP) was determined.


METHODS
The SHRSP were treated with an AT1 receptor antagonist (losartan: 100 mg/L in drinking water) from 2 to 4 weeks of age. After stopping treatment at 4 weeks of age, the control group and the losartan group were fed a commercial diet with tap water ad libitum until 10 weeks of age. Both the control and losartan groups were switched to 1% saline at the age of 10 weeks.


RESULTS
Salt loading was started at 10 weeks of age, with BP levels of 203+/-3 and 199+/-6 mm Hg for the control group and the losartan group, respectively, at that age. After 4 weeks of salt loading, BP levels were 253+/-7 mm Hg in the control group and 242+/-5 mm Hg in the losartan group, showing a mild elevation in the losartan group. The life span of the losartan group (104+/-78 days) was significantly greater than that of the control group (37+/-17 days). Plasma aldosterone concentrations of the losartan group were lower than those of the control group at 4 and 15 weeks of age.


CONCLUSIONS
We have demonstrated the renin-angiotensin-aldosterone system may play a key role in the establishment of end-organ salt sensitivity, and the period of lactation in critical for salt sensitivity in later life.
Otani
Lila
L
Division of Advanced Life Sciences, Graduate School of Agriculture, Kinki University, Nara, Japan.
Yasumatsu
Tomohide
T
Murakami
Megumi
M
Hayashi
Atsumi
A
Kimoto
Koichi
K
Murakami
Tetsuo
T
D000419:Albuminuria / Q000139:chemically induced; D000450:Aldosterone / Q000097:blood; D000704:Analysis of Variance; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D000833:Animals, Suckling; D000959:Antihypertensive Agents / Q000494:pharmacology; D015415:Biomarkers / Q000097:blood / Q000652:urine; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D019808:Losartan / Q000494:pharmacology; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012083:Renin / Q000097:blood / Q000187:drug effects; D017673:Sodium Chloride, Dietary / Q000009:adverse effects / Q000494:pharmacology*; D020521:Stroke / Q000139:chemically induced / Q000503:physiopathology*; D013997:Time Factors
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D015415:Biomarkers; D017673:Sodium Chloride, Dietary; D000450:Aldosterone; D012083:Renin; D019808:Losartan