What question did this study set out to answer?

To determine whether an angiotensin-converting enzyme inhibitor potentiates angiotensin receptor blocker–mediated increases in renal interstitial fluid bradykinin and cGMP levels.

August 1, 2001HypertensionOpen Access

Angiotensin-Converting Enzyme Inhibition Potentiates Angiotensin II Type 1 Receptor Effects on Renal Bradykinin and cGMP

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Population

Sodium-depleted, conscious Sprague-Dawley rats

Comparison

Infusion of valsartan, benazeprilate, or PD… vs Vehicle control

Design

Preclinical

Follow-up

60 minutes

Authors

HSHelmy M. SiragyGeneral / Preventive / Lipids MGMarc de GasparoGeneral / Preventive / Lipids MEMohamed A. ElkershAnimal Health Research Institute

Discussion

Member takes

Implication

Suggests synergistic renal effects with ACEI/ARB in rats; leaves open clinical translation to human hypertension.

Key Points

To determine whether an angiotensin-converting enzyme inhibitor potentiates angiotensin receptor blocker–mediated increases in renal interstitial fluid bradykinin and cGMP levels.
In vivo renal microdialysis was performed in conscious, sodium-depleted Sprague-Dawley rats, with each rat serving as its own control.
Animals received 60-minute infusions of the AT1 receptor blocker valsartan (0.17 mg/kg/min), the active ACE inhibitor metabolite benazeprilate (0.05 mg/kg/min), the AT2 receptor blocker PD 123,319 (50 µg/kg/min), or combinations.
Renal interstitial fluid levels of bradykinin and cGMP increased significantly over 1 hour following infusion of valsartan, benazeprilate, or both compared to vehicle control (P<0.01).
Co-infusion of benazeprilate and valsartan produced a supra-additive increase exceeding the sum of their individual effects, and this potentiation was completely abolished by PD 123,319.

Structured PICO

Population

Sodium-depleted, conscious Sprague-Dawley rats

Intervention

Infusion of valsartan (0.17 mg/kg per minute), benazeprilate (0.05 mg/kg per minute), or PD 123,319 (50 microg/kg per minute) alone or combined for 60 minutes

Comparator

Vehicle control (each animal served as its own control)

Outcome

Renal interstitial fluid (RIF) bradykinin (BK) and cGMP levelssurrogate

The combination of an ACE inhibitor and an ARB potentiates increases in renal interstitial fluid bradykinin and cGMP levels in a rat model.

Cite This Study

Siragy et al. (2001) studied this question.

synapsesocial.com/papers/6a7596c142ce5c1965dd89ce https://doi.org/10.1161/01.hyp.38.2.183

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Angiotensin-Converting Enzyme Inhibition Potentiates Angiotensin II Type 1 Receptor Effects on Renal Bradykinin and cGMP

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Angiotensin-Converting Enzyme Inhibition Potentiates Angiotensin II Type 1 Receptor Effects on Renal Bradykinin and cGMP

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Also Consider

Also Consider