Volume 4, Number 3, September 2003

The role of Ang (1-7) in mediating the chronic hypotensive effects of losartan in normal rats
John P Collister, Michael D Hendel

Hypothesis: The following studies were designed to test the hypothesis that Ang (1-7) contributes to the chronic hypotensive effects of the angiotensin II AT₁-receptor antagonist, losartan, in normal rats.
Introduction: We have previously shown a chronic, hypotensive response to the AT₁-receptor antagonist, losartan, in normotensive rats. The mechanism of this response is not completely understood. Previous studies by others have demonstrated a role for Ang (1-7) in the beneficial antihypertensive effects of angiotensin-converting enzyme (ACE) inhibition. This is thought to be due to vasodilatory effects of increased levels of Ang (1-7) during ACE inhibition. Since it has now been shown that Ang (1-7) levels are also increased during AT₁ antagonism, we designed experiments to test the hypothesis above.
Materials and methods: Sprague-Dawley rats were instrumented with venous catheters and radiotelemetric pressure transducers and commenced on a normal (0.4%) NaCl diet. Arterial pressure responses were measured in rats treated with losartan (10 mg/kg/day) (LOS rats, n=8) and compared with those treated with losartan and the Ang (1-7) antagonist, A779 (24 µg/kg/hour) (A779/LOS rats, n=11) for 10 days.
Results: By day 7 of treatment, mean arterial pressure had dropped by 27+1 mmHg in LOS rats, in contrast with a decrease of only 21+2 mmHg in A779/LOS rats. This attenuated response in rats treated with A779 became more prominent and continued through day 10 of losartan treatment.
Conclusion: These results support the hypothesis that the chronic hypotensive effects of losartan in normal rats are mediated in part through the actions of Ang (1-7).

JRAAS 2003;4:176-179.

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