Dose-Response Effects of Adrenergic and Cholinergic Stimulation on Atrial Natriuretic Peptide Secretion from Beating Isolated Guinea-Pig Atria

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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 α- and β-adrenoceptor agonists phenylephrine and isoprenaline, respectively. Adrenoceptor effects were further studied using the selective α- and β-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 × 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 × 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 152 ± 0.22 at 2 × 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 × 10−5 mol/l (P <0.05). After both α- and β-adrenoceptor blockade, adrenaline was still able to significantly stimulate atrial natriuretic peptide secretion and positive inotropy. There was no chronotropic effect of adrenaline in the presence of propranolol. Simultaneous α- and β-adrenoceptor blockade inhibited all the effects of adrenaline. 3. A significant correlation was observed between the absolute change in rate of contraction and the absolute change in atrial natriuretic peptide secretion upon stimulation with each of the drugs (r = 0.63, P < 0.001). A similar relationship between developed tension and atrial natriuretic peptide secretion could not be demonstrated. 4. In conclusion, secretion of atrial natriuretic peptide from guinea-pig atria was stimulated by adrenergic and inhibited by cholinergic agonists. The adrenergic response was mediated by both α- and β-adrenoceptor stimulation. The observed changes in the rate of contraction showed a significant correlation with atrial natriuretic peptide secretion.

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