Tertatolol potentiates exercise-induced atrial natriuretic peptide release by increasing atrial diameter in healthy subjects.
To evaluate the contribution of atrial distension and/or adrenergic mechanisms in the regulation of atrial natriuretic peptide (ANP) secretion, plasma immunoreactive ANP, norepinephrine (NE), epinephrine (E), and left atrial diameter were measured at rest, during, and after graded upright standardised bicycle exercise in 8 healthy male subjects after single-dose administration of placebo, tertatolol (5 mg), prazosin (1 mg), or combination of tertatolol (5 mg) and prazosin (1 mg). Systolic and diastolic left atrial diameters were measured before, during, and just after exercise by bidimensional echocardiography. Exercise raised plasma ANP concentrations. This rise was greater on tertatolol alone and tertatolol and prazosin than on placebo or prazosin alone: mean area under the plasma ANP concentration curve increased by 35% on tertatolol alone, 45% on tertatolol and prazosin when compared with placebo (p < 0.01), and by 82 and 94%, respectively, when compared with prazosin alone (p < 0.01). The rise in plasma ANP was greater during the postexercise period: 80% for tertatolol alone, 67% for tertatolol and prazosin when compared with placebo (p < 0.01) and 133 and 115%, respectively, when compared with prazosin alone (p < 0.01). The rise in plasma ANP was accompanied by an increase in both systolic and diastolic atrial diameters which was significantly greater on tertatolol alone and on the tertatolol and prazosin combination than on placebo or prazosin alone (p < 0.001). Beta-blockade alone did not affect plasma catecholamine concentrations but exercise-induced increase in plasma NE was significantly potentiated by prazosin and the prazosin and tertatolol combination, and that of plasma E by the prazosin and tertatolol combination.(ABSTRACT TRUNCATED AT 250 WORDS)
Berlin
I
I
Departments of Clinical Pharmacology, Hôpital Pitié-Salpêtrière, Paris, France.
Deray
G
G
Lechat
P
P
Maistre
G
G
Landault
C
C
Chermat
V
V
Brouard
R
R
Ressayre
C
C
Puech
A J
AJ
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000328:Adult; D016279:Atrial Function, Left / Q000187:drug effects*; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D004311:Double-Blind Method; D004452:Echocardiography; D004837:Epinephrine / Q000097:blood; D015444:Exercise / Q000502:physiology; D005080:Exercise Test; D006325:Heart Atria / Q000187:drug effects*; D006801:Humans; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009638:Norepinephrine / Q000097:blood; D011224:Prazosin / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology*; D011942:Receptors, Adrenergic, alpha / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D013876:Thiophenes
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D013876:Thiophenes; D009320:Atrial Natriuretic Factor; C005632:tertatolol; D009638:Norepinephrine; D011224:Prazosin; D004837:Epinephrine