EFFECTS OF THE (+/-)-, (+)- AND (-)-FORMS OF PROPRANOLOL, TIMOLOL AND METOPROLOL ON NORADRENERGIC TRANSMISSION IN THE RAT ISOLATED RIGHT VENTRICLE

  • 1 January 1984
    • journal article
    • research article
    • Vol. 270  (1) , 61-78
Abstract
The effects of the (.+-.)-, (+)- and (.sbd.)-forms of propranolol, timolol and metoprolol on noradrenergic transmission were studied in the rat isolated right ventricle. (+)- and (-)-propranolol (10-5 M) inhibited the accumulation of radioactivity from [3H]-noradrenaline [norepinephrine, NE]. The decline in the spontaneous outflow of radioactivity, following loading of the tissue with [3H]-NE was reduced by (+)- and (-)-propranolol (10-5 M), (+)-timolol (10-5 M), (.sbd.)-timolol (10-6-10-5 M) and (+)-metoprolol (10-5 M) increased the decline in outflow of radioactivity evoked by field stimulation in the absence, but not in the presence, of lignocaine (10-4 M), probably by decreasing nerve excitability. The ability of (.sbd.)-propranolol (10-5 M) to increase the decline in evoked outflow was also reduced in the presence of lignocaine. (+)-Propranolol, (+)-timolol and (-)-metoprolol reduced the contractile response to field stimulation by a similar percentage in the absence or presence of lignocaine. The ability of (-)-propranolol and (+)-metoprolol (10-5 M) to reduce contractile responses was decreased and abolished, respectively, by the addition of lignocaine. Evoked-outflow was not altered but contractile responses were inhibited by (-)-timolol (10-7-10-5 M) and (-)-metoprolol (10-5 M). Contractile responses to isoprenaline were not altered by (+)-propranolol, (+)-timolol (10-7 M) and (+)-metoprolol (10-7-10-6 M). (+)- or (-)-propranolol (10-7 M) and (+)-timolol (10-6 M) and no effect on the rate of beating to isoprenaline but reduced the force whereas (.+-.)-metoprolol (10-7 M) had no effect on the force but reduced the rate of beating. The rate of beating and force responses to isoprenaline were reduced by (.+-.)-, (+)-, (-)-propranolol (10-6 M), (.+-.)- or (-)-timolol (10-7-10-6 M), (.+-.)-metoprolol (10-6 M) and (-)-metoprolol (10-7-10-6 M). The rat isolated right ventricle, the (+)-isomers are active constituents of (.+-.)-propranolol and (.+-.)-timolol but not of (.+-.)-metoprolol.