Dose-response effects of adrenergic and cholinergic stimulation on atrial natriuretic peptide secretion from beating isolated guinea-pig atria.

1. The possible role of autonomic neurotransmitters in atrial natriuretic peptide secretion was investigated using spontaneously beating guinea-pig atria in vitro. Dose responses were determined for adrenaline, noradrenaline and acetylcholine and the selective alpha- and beta-adrenoceptor agonists phenylephrine and isoprenaline, respectively. Adrenoceptor effects were further studied using the selective alpha- and beta-adrenoceptor antagonists prazosin and propranolol, respectively, in conjunction with maximal adrenaline challenge. Results for rate and force of contraction and atrial natriuretic peptide secretion are expressed as a ratio (mean +/- SEM) of a 15 min treatment period (stage 2) to a corresponding pretreatment period (stage 1). 2. Adrenaline and noradrenaline caused dose-dependent increases in the rate and force of contraction and in atrial natriuretic peptide secretion with a peak secretory response at 2 x 10(-6) mol/l of 1.54 +/- 0.08 (P < 0.01) and 1.34 +/- 0.08 (P < 0.01) for adrenaline and noradrenaline, respectively. Acetylcholine decreased the rate and force of contraction, and ANP secretion was reduced to 0.47 +/- 0.06 at 3 x 10(-5) mol/l (P < 0.01). Isoprenaline increased the rate and force of contraction and atrial natriuretic peptide secretion with a peak secretory response of 1.52 +/- 0.22 at 2 x 10(-6) mol/l (P < 0.01). Phenylephrine increased the force but had no effect on the rate of contraction, and stimulated atrial natriuretic peptide secretion to 1.13 +/- 0.09 at 2 x 10(-5) mol/l (P < 0.05). After both alpha- and beta-adrenoceptor blockade, adrenaline was still able to significantly stimulate atrial natriuretic peptide secretion and positive inotropy.(ABSTRACT TRUNCATED AT 250 WORDS)