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.
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D004558:Electric Stimulation; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D011651:Pulmonary Artery / Q000294:innervation; D013564:Sympathetic Nervous System / Q000187:drug effects*; D013569:Synapses; D009435:Synaptic Transmission / Q000187:drug effects*
D000319:Adrenergic beta-Antagonists; D009638:Norepinephrine