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Direct chronotropic effects of atrial and C‐type natriuretic peptides in anaesthetized dogs
Author(s) -
Beaulieu Pierre,
Cardinal René,
Léan André,
Lambert Chantal
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb15605.x
Subject(s) - chronotropic , medicine , endocrinology , atrial natriuretic peptide , propranolol , angiotensin ii , atropine , prazosin , tachyphylaxis , chemistry , receptor , heart rate , antagonist , blood pressure
1 . The chronotropic effects of atrial natriuretic peptide (ANP) and C‐type natriuretic peptide (CNP) were investigated using injections (50 μg in 1 ml of Tyrode solution as bolus over 1 min) directly into the sinus node artery of 21 anaesthetized and vagotomized dogs which had been pretreated with a β‐adrenoceptor antagonist. The injections were also repeated following: (a) α‐adrenoceptor antagonism (prazosin) and muscarinic receptor antagonism (atropine); (b) inhibition of prostaglandin synthesis (indomethacin); (c) angiotensin II AT 1 receptor antagonism (losartan); (d) histamine H 1 (mepyramine) and H 2 (cimetidine) receptor antagonism. 2 . The results obtained indicate that ANP had no significant effect on the basal sinus rate, whereas CNP produced a slight but significant increase of 12 ± 2 beats min −1 . The effect of CNP was long‐lasting (return to pre‐injection levels after maximum effect in 17 ± 3 min) and was not influenced by the various antagonists mentioned above. 3 . During in vitro experiments on spontaneously beating right atria isolated from 6 dogs, the injection of CNP (50 μg in 1 ml of Tyrode solution) into the sinus node artery produced an increase in atrial rate of 14 ± 1 beats min −1 . 4 . The results of this work indicate that CNP exerts a significant and prolonged positive chronotropic effect both in vivo and in vitro . Other studies are required to elucidate the mechanism of action of CNP on the heart conduction system, to ascertain the presence of natriuretic peptide receptor B in the region of the sinoatrial node and to determine the role of CNP in the control of heart rate.