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November 1, 1999Hypertension

AT2Receptor Stimulation Enhances Antihypertensive Effect of AT1Receptor Antagonist in Hypertensive Rats

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Why the study?

Does AT2 receptor activation enhance the antihypertensive effects of AT1 receptor antagonists in hypertensive rats?

Population

Spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY)

Comparison

AT1 receptor antagonist candesartan plus AT2… vs Candesartan alone, CGP42112 alone, or saline

Design

Preclinical

Follow-up

4-day protocol

Authors

MBMelissa BarberPeter MacCallum Cancer CentreDSDonella B SampeyMonash UniversityRWRobert E. WiddopGeneral Cardiology

Discussion

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Overview

AT2 agonism may enhance low-dose candesartan effects in SHR; hypothesis-generating and requires human trials before any clinical consideration.

Key Points

  • This study aims to explore how AT2 receptor activation influences the effectiveness of AT1 receptor antagonists in managing hypertension.
  • Measured mean arterial pressure and heart rate over 4-day protocol in spontaneously hypertensive rats and Wistar-Kyoto rats.
  • Administered drug combinations of AT1 receptor antagonist candesartan and AT2 receptor agonist CGP42112.
  • Confirmed involvement of AT2 receptors using antagonist PD123319.
  • In spontaneously hypertensive rats, a lower dose of candesartan (0.01 mg/kg) showed enhanced antihypertensive effects when combined with CGP42112.
  • Candesartan alone at 0.1 mg/kg caused a significant decrease in MAP, with no effect from CGP42112.
  • The facilitation of the antihypertensive effect was abolished by the co-infusion of PD123319.

Structured PICO

Does AT2 receptor activation enhance the antihypertensive effects of AT1 receptor antagonists in hypertensive rats?

P
Population
Spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY)
I
Intervention
AT1 receptor antagonist candesartan (0.01 or 0.1 mg/kg IV) plus AT2 receptor agonist CGP42112 (1 microg/kg per minute)
C
Comparator
Candesartan alone, CGP42112 alone, or saline
O
Outcome
Mean arterial pressure (MAP) and heart ratesurrogate

AT2 receptor activation facilitates the initial blood pressure-lowering effect of AT1 receptor antagonists in spontaneously hypertensive rats.

Cite This Study

Barber et al. (1999) studied this question.

synapsesocial.com/papers/6a74ab718d2049c8dd03336chttps://doi.org/10.1161/01.hyp.34.5.1112
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Subtype 2 of angiotensin II receptors controls pressure-natriuresis in rats.1995 · 139 citations
  2. 2Regional Hemodynamic Effects of the AT<sub>1</sub>Receptor Antagonist CV-11974 in Conscious Renal Hypertensive Rats1995 · 21 citations
  3. 3Inhibition of the haemodynamic effects of angiotensin II in conscious rats by AT<sub>2</sub>‐receptor antagonists given after the AT<sub>1</sub>‐receptor antagonist, EXP 31741992 · 34 citations
  4. 4Effects of angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor antagonists in rats with heart failure. Role of kinins and angiotensin II type 2 receptors.1997 · 606 citations
  5. 5Angiotensin type 2 receptors mediate depressor phase of biphasic pressure response to angiotensin1993 · 136 citations