Occurrence of dopaminergic (D(2)) receptors within the rabbit pulmonary circulation.

The pharmacological characteristics and the microanatomical localization of dopamine D(2)-like receptors, or more correctly spiroperidol binding sites, in the rabbit pulmonary circulation were studied using combined marker binding and light microscopy autoradiography with [((3))H]-spiroperidol (spiperone) as marker. The marker was bound to the samples of the pulmonary artery in a manner consistent with the labelling of dopamine D(2)-like receptors with an equilibrium dissociation constant (K(d)) of about 2.4+/-0.07 nmol/l and a maximum density of binding sites of 65+/-4.5 fmol/mg tissue. Samples of bronchial artery show the same results as those of the pulmonary artery. In contrast, binding experiments made with samples of rabbit lung (capillary of the microcirculation), of pulmonary veins and/or of bronchial veins did not allow the evaluation of specific binding.Autoradiography, observed with light microscopy, showed the development of specific silver grains within the whole wall of extraparenchymal branches of the pulmonary artery and/or of the bronchial artery. Development of silver grains was inhibited by compounds active on the dopamine receptors. The greater sensitivity to displacement by domperidone, haloperidol, and bromocriptine than to displacement by N-propyl-nor-apomorphine, quinpirole and clozapine suggests that the binding sites observed in extraparenchymal, large and medium-sized branches of the rabbit pulmonary and bronchial arteries belong, likely, to the dopamine D(2) receptor subtype. Quantitative analysis of images let us count the amount of these receptors in many samples of the pulmonary and/or bronchial arteries.

Pulmonary vascular remodeling distal to pulmonary artery ligation is accompanied by upregulation of endothelin receptors and nitric oxide synthase.

There is increasing evidence that the pathogenesis and progression of many forms of pulmonary vasculopathy are related to abnormalities in endothelial mediators, including endothelin-1 (ET-1) and nitric oxide (NO). Using a rat model of chronic unilateral pulmonary artery ligation, we investigated the role of ET-1 and NO in postobstructive pulmonary vasculopathy (POPV). Eight months after a left thoracotomy with either left main pulmonary artery ligation (ligated group) or no ligation (sham group), rat lungs, including those contralateral to the ligation (hyperperfused group), were fixed and mounted for histologic sectioning. Morphometric measurements were carried out by computer-assisted image analysis and immunohistochemical staining was performed using specific antibodies against ET-1, ETA, and EBB receptors, and endothelial NO synthase (eNOS). Compared to sham lungs, the ligated lungs showed (1) an increase in muscular, adventitial, and intimal thickness of pulmonary artery; (2) increase in external diameter of the bronchial artery (39.8 +/- 2.2 microns vs. 16.8 +/- 0.9 microns in sham group; P < .005) and number of bronchial arteries per bronchiole (3.21 +/- mu 0.26 vs. 1.86 +/- mu 0.21 in sham group; P < .001); and (3) increase in the intensity of eNOS and ETA, B receptor immunoreactivity. No morphometric or immunohistochemical differences were observed between the hyperperfused and sham lungs. These findings suggest that increased synthesis of endothelial NO may serve as a compensatory mediator in ET-1-mediated vascular remodeling.