What question did this study set out to answer?

To evaluate the role of angiotensin II AT2 receptors in blood pressure regulation and assess whether AT2 receptors contribute to the blood pressure-lowering effect of AT1 receptor blockade.

December 1, 1998Journal of Hypertension

Role of the angiotensin II AT2-subtype receptors in the blood pressure-lowering effect of losartan in salt-restricted rats

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Why the study?

Does AT2 receptor blockade with PD123319 offset the blood pressure-lowering effect of losartan in salt-restricted rats?

Population

52 Sprague-Dawley rats, preliminarily salt-restricted to enhance circulating and tissue renin-angiotensin…

Comparison

Selective AT2 receptor antagonist PD123319 and… vs Control group and losartan + vehicle group.

Design

Preclinical

Follow-up

1 week

Authors

BGBruna GigantePreventive Cardiology OPOrnella PirasAzienda Ospedaliera Sant'Andrea PPPaola De PaolisUniversity of Naples Federico II

Discussion

Member takes

Implication

AT2 contribution to ARB effects is unproven in humans; leaves open mechanistic role pending clinical studies.

Key Points

To evaluate the role of angiotensin II AT2 receptors in blood pressure regulation and assess whether AT2 receptors contribute to the blood pressure-lowering effect of AT1 receptor blockade.
Studied 52 salt-restricted Sprague-Dawley rats, including intact and bilaterally nephrectomized animals, over a 1-week treatment period.
Administered the selective AT1 antagonist losartan (10 mg/kg/day), the selective AT2 antagonist PD123319 (50 μg/kg/min), combined losartan plus PD123319, or vehicle controls.
Losartan monotherapy significantly reduced blood pressure in intact (P < 0.001) and nephrectomized rats (P < 0.05), whereas PD123319 alone significantly increased blood pressure in both intact and nephrectomized models (both P < 0.001).
Co-infusion of PD123319 with losartan significantly raised blood pressure compared to losartan alone and losartan plus vehicle (P < 0.001), neutralizing the blood pressure-lowering response to pre-treatment levels (P = ns).

Structured PICO

Does AT2 receptor blockade with PD123319 offset the blood pressure-lowering effect of losartan in salt-restricted rats?

Population

52 Sprague-Dawley rats, preliminarily salt-restricted (SR) to enhance circulating and tissue renin-angiotensin system activity, including intact and bilaterally nephrectomized (NX) models.

Intervention

Selective AT2 receptor antagonist PD123319 (50 microg/kg/min) and AT1 receptor antagonist losartan (10 mg/kg/day), alone or in combination (Los + PD), maintained for 1 week.

Comparator

Control group (n=7) and losartan + vehicle group (n=10).

Outcome

Blood pressure (BP)surrogate

AT2 receptors contribute to the hypotensive effects of the AT1 receptor antagonist losartan in salt-restricted rats.

Cite This Study

Gigante et al. (1998) studied this question.

synapsesocial.com/papers/6a74bc3433d16877c7f54b65 https://doi.org/10.1097/00004872-199816121-00027

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Role of the angiotensin II AT2-subtype receptors in the blood pressure-lowering effect of losartan in salt-restricted rats

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Role of the angiotensin II AT2-subtype receptors in the blood pressure-lowering effect of losartan in salt-restricted rats

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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