Paroxysms of atrial tachycardia are oftentimes associated with polyuria. The plasma levels of the potent diuretic hormone, atrial natriuretic peptide (ANP), are elevated during episodes of atrial tachycardia, suggesting that ANP may play a role in mediating the diuresis. The mechanism of enhanced ANP secretion associated with atrial tachycardia is not known. We examined the effect of altering the pacing frequency of isolated left rat atria on ANP secretion. Atria were suspended between an electrode and hook connected to a force transducer and superfused with medium 199. The ANP content of the superfusate was measured by radioimmunoassay. Increasing the frequency of pacing from 2 to 4 Hz resulted in a 46 +/- 5% (means +/- SE, n = 9) rise in immunoreactive ANP secretion above base line (P less than 0.01). Lowering the frequency from 4 to 2 Hz lowered immunoreactive ANP secretion by 36 +/- 3% (n = 6) relative to base line (P less than 0.02). Incremental increases in the pacing frequency from 2 to 8 Hz resulted in a continual rise in immunoreactive ANP with a peak increase of 191 +/- 6% of base line (n = 8) at 8 Hz. To examine the possibility that release of norepinephrine or acetylcholine from endogenous nerves mediated this effect, the atria were superfused with the combination of 0.1 microM propranolol, 1.0 microM phentolamine, and 10 microM atropine. The concentrations of the antagonists were 125-fold or higher than the dissociation constant for binding to receptors.(ABSTRACT TRUNCATED AT 250 WORDS)