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)
Speake
P F
PF
Department of Physiological Sciences, University of Manchester, U.K.
Pirie
S C
SC
Kibble
J D
JD
Muneer
A
A
Taylor
D
D
Birring
S
S
Green
R
R
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010277:Parasympathomimetics / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011941:Receptors, Adrenergic / Q000187:drug effects; D011950:Receptors, Cholinergic / Q000187:drug effects; D013566:Sympathomimetics / Q000494:pharmacology
D010277:Parasympathomimetics; D011941:Receptors, Adrenergic; D011950:Receptors, Cholinergic; D013566:Sympathomimetics; D010656:Phenylephrine; D009320:Atrial Natriuretic Factor; D011433:Propranolol; D007545:Isoproterenol; D000109:Acetylcholine; D009638:Norepinephrine; D011224:Prazosin; D004837:Epinephrine