What is the clinical evidence from this study?

Study design: Other. Population: Anesthetized rats. Intervention: Endothelin-1 antiserum vs. Control serum. Primary outcome: Plasma ANP concentration (basal and volume-stimulated) (p=<.01).

September 1, 1993Open Access

Endothelin antiserum decreases volume-stimulated and basal plasma concentration of atrial natriuretic peptide.

Q: What are the key findings of this study?

Intravenous injection of endothelin-1 antiserum in anesthetized rats reduced basal plasma ANP concentration and attenuated volume-stimulated ANP release compared to control serum (P<0.01).

Key Result

Intravenous injection of endothelin-1 antiserum in anesthetized rats reduced basal plasma ANP concentration and attenuated volume-stimulated ANP release compared to control serum (P<0.01).

Structured PICO

Does intravenous injection of antiserum against ET-1 decrease basal and volume-stimulated plasma concentrations of ANP in anesthetized rats?

Population

Pentobarbital-anesthetized Wistar rats used to test the role of endogenous ET-1 in the regulation of ANP release.

Intervention

Intravenous injection of antiserum against ET-1

Comparator

Control rat serum

Outcome

Plasma ANP concentration (basal and volume-stimulated)surrogate

Endogenous endothelin-1 acts as a physiological modulator of both basal and volume-stimulated atrial natriuretic peptide release in vivo.

Main Result

p-value: p=<.01

Abstract

BACKGROUND: Endothelin-1 (ET-1) is the most powerful factor known to release atrial natriuretic peptide (ANP) in vivo and in cultured cardiac myocytes or preparations of atrium. We tested the role of endogenous ET-1 in the regulation of ANP release by passive immunization in anesthetized rats. METHODS AND RESULTS: Intravenous injection of antiserum against ET-1 was shown to decrease basal and volume-stimulated plasma concentrations of ANP, whereas control serum was without effect. Antiserum generated in rabbits cross-reacted 100% with endothelin-2 and -3. In pentobarbital-anesthetized Wistar rats treated with ET-1 antiserum, plasma ANP concentration measured by radioimmunoassay was reduced by 37% from starting level after 10 minutes and by 30% after 60 minutes. Control rat serum had no effect on plasma ANP. Rapid intravenous infusion of 8 mL of 0.9% NaCl caused a sixfold increase of plasma ANP concentration in control rats but only twofold in rats pretreated with ET-1 antiserum (P < .01). This effect of ET-1 antiserum was dose dependent. ET-1 antiserum changed neither blood pressure nor heart rate significantly in anesthetized rats. Pretreatment with ET-1 antiserum did not affect the initial hypotensive response to intravenous ET-1 0.5 nmol/kg but significantly attenuated the subsequent hypertensive response to endothelin. CONCLUSIONS: Endothelin may be a physiological modulator of both basal and stimulated ANP release.