What is the clinical evidence from this study?

Study design: Other. Population: Cardiac overload. Intervention: Direct myocardial stretch vs. Control values (before stretch). Primary outcome: Rate of IR-ANP and IR-BNP release and BNP gene expression (mRNA levels) (4.5-fold increase in BNP mRNA at 2 hours, p=< 0.001).

September 1, 1993

Atrial stretch induces rapid increase in brain natriuretic peptide but not in atrial natriuretic peptide gene expression in vitro.

Q: What are the key findings of this study?

Direct atrial stretch in perfused rat hearts rapidly stimulated BNP gene expression (4.5-fold increase at 2 hours, p<0.001) and the release of both ANP and BNP, without changing ANP mRNA levels.

Key Result

Direct atrial stretch in perfused rat hearts rapidly stimulated BNP gene expression (4.5-fold increase at 2 hours, p<0.001) and the release of both ANP and BNP, without changing ANP mRNA levels.

Structured PICO

Population

Perfused rat heart preparations subjected to stepwise distension of the right atrium to simulate cardiac overload.

Intervention

Short-term direct myocardial stretch (increase in right atrial pressure by 3.6 mm Hg for up to 2 hours)

Comparator

Unstretched control state

Outcome

Atrial ANP and BNP synthesis and release (IR-ANP and IR-BNP release into perfusate, and auricular mRNA levels)surrogate

Direct atrial stretch rapidly stimulates BNP gene expression and secretion independently of humoral or neural factors, while ANP gene expression remains unchanged.

Main Result

Effect estimate: 4.5-fold increase in BNP mRNA at 2 hours

p-value: p=< 0.001

Abstract

Pressure and volume overload in vivo is characterized by induction of the expression of two cardiac hormones, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), but whether stretch directly or other pathophysiological factors associated with cardiac overload cause the activation of these genes is not known. In the present study we examined the effect of short-term (from 30 min to 2 h) direct myocardial stretch on atrial ANP and BNP synthesis and release in modified perfused rat heart preparation that enabled the stepwise distension of the right atrium by pressures approximating those found in vivo. The increase in right atrial pressure by 3.6 mm Hg for 2 h resulted in a 3.3- (p < 0.001) and 1.7-fold (p < 0.02) increase in the rate of IR-ANP and IR-BNP release, respectively, into the perfusate. The maximal increase in both ANP and BNP release was seen after 20 min distension. Thereafter the perfusate IR-ANP and IR-BNP concentration gradually decreased, reaching control values within 2 hours. Chromatographic analysis showed that the hearts primarily release the active, processed 28- and 45-amino acid ANP- and BNP-like peptides, respectively, both before and during atrial stretch. Atrial stretch induced rapid stimulation of BNP gene expression: 1.9- (p < 0.001) and 4.5-fold (p < 0.001) increase in right auricular BNP mRNA levels after 1.0 and 2.0 hours' stretching, respectively, was found on Northern blot analysis, while no change was seen after 30 min distension. In contrast, stretching for up to 2 h did not change auricular ANP mRNA, IR-ANP or IR-BNP levels. Our results show for the first time that atrial stretch induces rapid stimulation of both synthesis and secretion of BNP. The induction of BNP gene expression in the very early stages of cardiac overload mimics the induction of protooncogenes and occurred without involvement of humoral or neural factors. The lack of response of atrial ANP mRNA levels demonstrates that the regulation of BNP gene expression differs from that of ANP.

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