Atrial natriuretic peptide decreases contractility of cultured chick ventricular cells.
To determine whether atrial natriuretic peptide (ANP) has an inotropic effect, the contractility of spontaneously beating cultured chick embryo ventricular cells was studied in response to rat-ANP (1-23) superfused at concentrations ranging from 10(-10) M to 2.5 x 10(-7) M. r-ANP reversibly decreased contractility with a threshold concentration of 10(-8) M; at the highest concentration, r-ANP decreased contractility to a moderate extent (-30 +/- 4%) r-ANP increased dose-dependently intracellular cGMP levels. Stimulation of contractility with [Ca2+], the calcium-channel agonist BAY K 8644 or isoproterenol attenuated to various degrees the inhibitory effect of r-ANP. By contrast, the inhibitory effect of r-ANP on contractility was unchanged or even enhanced after stimulation of contractility by angiotensin II. There was no difference in r-ANP-induced increase in cGMP whether cells were pre-incubated with angiotensin II or not. These results indicate that r-ANP was able to decrease contractility of cultured cardiac myocytes and suggest a preferential antagonism of the inotropic effect of angiotensin II.
Vaxelaire
J F
JF
INSERM U228, Paris, France.
Laurent
S
S
Lacolley
P
P
Briand
V
V
Schmitt
H
H
Michel
J B
JB
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D002642:Chick Embryo; D000242:Cyclic AMP / Q000032:analysis; D006152:Cyclic GMP / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects*; D006352:Heart Ventricles / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects*
D015220:Calcium Channels; D000804:Angiotensin II; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009320:Atrial Natriuretic Factor; D000242:Cyclic AMP; D006152:Cyclic GMP; D007545:Isoproterenol; D002118:Calcium