Adrenergic transmission failure via the blockade of presynaptic beta receptors in guinea-pig pulmonary arteries.

Mechanisms related to the inhibitory actions of low concentrations of l- and d-propranolol on adrenergic transmission were investigated in isolated preparations of guinea-pig pulmonary arteries. In sympathetic nerve-radial muscle preparations, l-propranolol (3.3 X 10(-8) and 10(-7) M) dose-dependently inhibited by 15 to 20% contractile responses to nerve stimulation (1 Hz, 2-msec pulse width, 100-sec period and 30-min intervals) 30 and 60 min after the addition, whereas 3.3 X 10(-7) M produced a maximal inhibition. Contractile responses to cumulatively applied norepinephrine were not modified by pretreatment with l-propranolol (10(-7) - 10(-6) M). d-Propranolol (10(-7) M) produced no inhibition of adrenergic transmission. In superfused spiral preparations preloaded with [3H]norepinephrine, l-isoproterenol (3 X 10(-8) - 10(-6) M) dose-dependently facilitated total 3H efflux by transmural field stimulation by 10 to 35% under the same conditions; this facilitation was antagonized by l-propranolol (10(-7) M) but not by d-propranolol (10(-7) M). Phentolamine (3 X 10(-6) M) increased 3H efflux by approximately 3-fold. In the presence of phentolamine, l-propranolol (10(-7) M) significantly inhibited 3H efflux, whereas d-propranolol (10(-7) M) produced no effect. Presynaptic beta adrenoceptors are present on sympathetic nerve endings which innervate guinea-pig pulmonary arteries and low concentrations of propranolol inhibit adrenergic transmission via blockade of these receptors.