Cardiovascular reactivity after blockade of angiotensin AT1 receptors in the experimental model of tilting test in conscious rats

Abstract

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 degrees 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.

Figure 1

Effects on baseline cardiovascular variables evoked by treatment with atenolol plus prazosin (2.5 and 0.1 mg kg⁻¹, n=5), losartan (1 and 10 mg kg⁻¹, n=6) or telmisartan (1 and 10 mg kg⁻¹, n=5) in conscious normotensive rats. Values represent the mean±s.e.mean. ^*P<0.05 compared with the vehicle group (0.9% NaCl, 1 ml kg⁻¹; n=7). One-way analysis of variance followed by Newman–Keuls test.

Figure 2

Changes in MAP and HR caused by orthostatic stress (tilt) in conscious rats after intravenous injection of vehicle (0.9% NaCl, 1 ml kg⁻¹; n=7) and atenolol plus prazosin (2.5 and 0.1 mg kg⁻¹ respectively, n=5). Bar indicates the duration of the maneuvre (0–15 min). ^*P<0.05 vs baseline; ^#P<0.01 vs vehicle group. HR, heart rate; MAP, mean arterial pressure.

Figure 3

Effect of oral treatment with losartan (1 and 10 mg kg⁻¹, n=6) and telmisartan (1 and 10 mg kg⁻¹, n=5) on the pressor response to Ang II (0.01, 0.1 and 0.5 μg kg⁻¹, intravenous) in conscious normotensive rats. Values represent the mean±s.e.mean. ^*P<0.05 compared with control; ^**P<0.01 compared with control; ^ΦP<0.001 compared with control; ^#P<0.05 telmisartan vs losartan. Ang II, angiotensin II.

Figure 4

Changes in MAP and HR caused by orthostatic stress (tilt) in conscious rats after oral treatment with losartan (1 mg kg⁻¹, n=6), telmisartan (1 mg kg⁻¹, n=5) or vehicle (0.9% NaCl, 1 ml kg⁻¹; n=7). Values are mean±s.e.mean. Bar indicates the duration of the maneuvre (0–15 min). ^*P<0.05 losartan vs baseline; ^#P<0.05 telmisartan vs baseline; ⁺P<0.01 losartan vs vehicle; ^ΦP<0.01 telmisartan vs vehicle. HR, heart rate; MAP, mean arterial pressure.

Figure 5

Changes in MAP and HR caused by orthostatic stress (tilt) in conscious rats after oral treatment with losartan (10 mg kg⁻¹, n=6), telmisartan (10 mg kg⁻¹, n=5) or vehicle (0.9% NaCl, 1 ml kg⁻¹; n=7). Values are mean±s.e.mean. Bar indicates the duration of the maneuvre (0–15 min). ^**P<0.01 losartan vs baseline; ^#P<0.05 telmisartan vs baseline; ⁺P<0.01 losartan vs vehicle; ^ΦP<0.01 telmisartan vs vehicle. HR, heart rate; MAP, mean arterial pressure.