Cardiovascular reactivity after blockade of angiotensin AT 1 receptors in the experimental model of tilting test in conscious rats

Background and purpose: Studies have shown that the angiotensin II AT 1 receptor antagonist, losartan, accentuates the hypotensive response in the orthostatic stress test (tilt) performed in anaesthetized rats. The same effect was not reported with other AT 1 antagonists. The aim of this study was to re‐evaluate the effects of AT 1 receptor blockade on the cardiovascular response to tilt in a model developed for conscious rats. Experimental approach: Rats ( n =5–7 per group) were instrumented for infusion of drugs and recording of cardiovascular parameters and, after recovery, placed in a plastic tube positioned over the tilt board. The tilt test was conducted by raising the head side of the tilt board from horizontal position to 75° head up position for 15 min. Key results: Compared with control group (NaCl 0.9%, 1 ml kg −1 ), oral treatment with 1 mg kg −1 per day of losartan or telmisartan did not alter the blood pressure response during tilt. With the 10 mg kg −1 dose, both antagonists altered the blood pressure response during tilt (mean maximum changes −11±3 mm Hg; P <0.01). A post‐tilt hypotension was observed with both doses in losartan and telmisartan groups (−13±1 and −9±2 mm Hg, respectively; P <0.01). Conclusions and implications: The present results indicate that the effect of losartan on the cardiovascular reactivity to tilt shares a similar profile to that of other AT 1 antagonists. Evidence discussed addresses the importance of using a conscious model for testing the influence of antihypertensive drugs on the cardiovascular reactivity to orthostatic challenges. British Journal of Pharmacology (2008) 153 , 966–971; doi: 10.1038/sj.bjp.0707652 ; published online 14 January 2008