[Inhibitory effect of propranolol on myocardial relaxation not mediated by beta blockade].
The effect of d- and d,l-propranolol (10(-5)M) on myocardial relaxation was studied in the isolated cat heart beating at constant rate and perfused at constant coronary flow. Infusion of d,l-propranolol 10(-5)M produced a significant decrease in maximal velocity of contraction (+T) of 48 +/- 1.5%, P less than 0.05, and a proportionally greater decrease in maximal velocity of relaxation (-T) of 58 +/- 2%, with a significant increase in the ratio between both maximal velocities (+T/-T) of 28.4 +/- 6.2% (from 1.35 +/- 0.03 to 1.74 0.09). The time constant of tension decline computed from the time of -T (Tau) was significantly prolonged by 64 +/- 17.5% (from 38 +/- 1.4 to 61 +/- 6 msec) (P less than 0.05). Similar results were obtained with d-propranolol (10(-5)M). A decrease in +T of 52.2 +/- 4.1% elicited by perfusion with low calcium (0.05 mM) also produced a slight increase in +T/-T and Tau by 11 +/- 4.5% and 27 +/- 6% respectively, P less than 0.05). These increases were, however, lower than those produced by both d,l- and d-propranolol (P less than 0.05). The effect of low calcium on +T, +T/-T and Tau were fully reversible, whereas the complete reversal by calcium of the negative inotropic effect of d- and d,l-propranolol did not reverse the significant decrease in -T and increase in +T/-T, and Tau elicited by the drug. Similar results were obtained in catecholamine depleted hearts. d-propranolol (10(-5)M) did not affect the calcium sensitivity of the chemically skinned cat right ventricular trabeculae. The calcium uptake of cat cardiac sarcoplasmic reticulum was significantly inhibited by d-propranolol from a concentration of 3 X 10(-4) M. The results suggest that propranolol 10(-5)M has an antirelaxant effect, not mediated by its negative inotropic action and independent of its beta blocking action. This antirelaxant effect might be mediated by the SR calcium uptake inhibition produced by the drug and might be a possible mechanism by which high concentrations of these agents negatively affect myocardial contractility.
Pedroni
P
P
Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, Argentina.
Mattiazzi
A
A
Gende
O A
OA
Cingolani
H E
HE
D000818:Animals; D002118:Calcium / Q000493:pharmacokinetics / Q000494:pharmacology; D002415:Cats; D003864:Depression, Chemical; D009200:Myocardial Contraction / Q000187:drug effects*; D011433:Propranolol / Q000494:pharmacology*; D012110:Reserpine / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000187:drug effects* / Q000502:physiology
D012110:Reserpine; D011433:Propranolol; D002118:Calcium
Efecto inhibitorio del propranolol sobre la relajación miocárdica no mediado a través del bloqueo beta.