Influence of 5- and 6-hydroxydopamine on adrenergic transmission and nerve terminal morphology in the canine pulmonary vascular bed.
We studied the effects of 5- and 6-hydroxydopamine on adrenergic neurotransmission, fluorescence histochemistry, and nerve terminal ultrastructure in the canine pulmonary vascular bed. Fluorescence histochemistry on stretched preparations and sections of intrapulmonary artery and vein demonstrated that these vessels are well supplied with adrenergic nerves electron microscopy revealed adrenergic terminals in the adventitia and outer third of the media in the artery, but only in the adventitia in the vein. Adrenergic terminals in artery and vein contained many small and a few large dense-core vesicles. At least 20% of the terminals in the artery contained many small agranular vesicles and a few large opaque vesicles; this suggests that they were of the cholinergic type; Such terminals were not found in intrapulmonary veins. Under conditions of controlled blood flow, stimulation of the sympathetic nerves to the lung and intralobar injection of norepinephrine increased pressure in the perfused lobar artery and small intrapulmonary vein in a stimulus-related manner. The rise in pressure in the lobar artery and vein in response to nerve stimulation was blocked after administration of either 5- and 6-hydroxydopamine; Neither agent modified the response of the pulmonary vascular bed to norepinephrine; In contrast, the rise in pressure in the lobar artery and vein in response to both norepinephrine and to nerve stimulation was blocked by phenoxybenzamine, an alpha-receptor blocking agent. The attenuated neurogenic vasoconstrictor response in dogs treated with 5- and 6-hydroxydopamine was associated with a marked decrease in intensity of fluorescence of the abundant adrenergic innervation in both intrapulmonary artery and vein, and with the appearance of an osmiophilic material in dense-core vesicles of adrenergic terminals in artery and vein. We believe that these data suggest that 5- and 6-hydroxydopamine interfere with adrenergic transmission in intrapulmonary vessels by depleting norepinephrine from adrenergic terminals. Furthermore, we conclude from hemodynamic, histochemical, and ultrastructural studies that vasomotor tone in the pulmonary vascular bed can be regulated by the sympathetic nervous system.
D000818:Animals; D001369:Axons / Q000648:ultrastructure; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D005260:Female; D006892:Hydroxydopamines / Q000494:pharmacology*; D008297:Male; D009411:Nerve Endings / Q000648:ultrastructure*; D009638:Norepinephrine / Q000494:pharmacology; D010643:Phenoxybenzamine / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects / Q000294:innervation* / Q000648:ultrastructure; D011667:Pulmonary Veins / Q000187:drug effects / Q000294:innervation* / Q000648:ultrastructure; D013233:Stellate Ganglion / Q000502:physiology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000648:ultrastructure*; D009435:Synaptic Transmission / Q000187:drug effects*; D014655:Vascular Resistance / Q000187:drug effects
D006892:Hydroxydopamines; D010643:Phenoxybenzamine; D009638:Norepinephrine