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Circ Res. 1989 Apr;64(4):799-805.

Chronotropic stimulation: a primary effector for release of atrial natriuretic factor.

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  • 1Department of Pharmacology, Merck Sharp & Dohme Research Laboratories, West Point, Pennsylvania.


Release of atrial natriuretic factor (ANF) following an elevation in heart rate is thought to be mediated primarily by a change in atrial stretch. To evaluate the direct effect of chronotropic stimulation on ANF release, isolated rat left atria were electrically paced (1-9 Hz) at constant resting tension (0.5-4 g), and the amount of immunoreactive ANF (IRANF) released at each frequency and tension was quantitated with a sensitive radioimmunoassay. Our results show that at controlled resting tensions greater than 1 g, chronotropic stimulation increased IRANF secretion in a manner dependent on the pacing frequency; rapid atrial rates (e.g., 8 and 9 Hz) were necessary to release ANF at tensions of 1 g or less. Resting tension influenced the magnitude of the secretory response to electrical stimulation. Release of IRANF with contraction frequency was transient in nature and, at high frequencies, was associated with a decrease in developed (systolic) tension in accordance with the negative force-frequency relation inherent in the rat heart. When evaluated at a single diastolic tension and pacing frequency, IRANF release was positively correlated with systolic tension. ANF released under in vitro conditions was approximately 3,000 Da, in agreement with the size of the physiologically circulating form. In atria from reserpinized rats, evidence for involvement of catecholamines in chronotropic-stimulated ANF release was suggested. The presence of lidocaine (5 x 10(-4) M) had no effect on rate-induced ANF secretion. Therefore, chronotropic stimulation releases ANF independently of changes in atrial stretch. The magnitude of this response depends on a combination of pacing frequency and diastolic tension.(ABSTRACT TRUNCATED AT 250 WORDS)

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