DENSITY AND LOCALIZATION OF CALCIUM CHANNELS OF THE L-TYPE IN HUMAN PULMONARY-ARTERY

The pharmacological profile and the anatomical localization of Ca2+ ch annels of the L-type were investigated in the human pulmonary artery t o identify possible mechanisms involved in the regulation of the pulmo nary vascular tone. Analysis was performed on slide-mounted frozen sec tions of human pulmonary artery using radioligand binding assay techni ques associated with light microscope autoradiography. [H-3]-nicardipi ne was used as ligand. Human renal and right coronary arteries also we re used as systemic reference arteries. Binding of [H-3]-nicardipine t o sections of human pulmonary artery was time-, temperature- and conce ntration-dependent, saturable and reversible. In the human pulmonary a rtery, the apparent equilibrium dissociation constant (K-d) was 0.12 /- 0.02 nM and the maximum density of binding sites (B-max) was 38.15 +/- 2.25 fmol/mg tissue. K-d values were 0.3 +/- 0.01 nM and 0.5 +/- 0 .02 in the human renal artery and right coronary artery respectively. B-max values were 248 +/- 16 fmol/mg tissue and 173 +/- 9.5 fmol/mg ti ssue in the human renal artery and right coronary artery respectively. The pharmacological profile of [H-3]-nicardipine binding to sections of human pulmonary artery was consistent with the labeling of Ca2+ cha nnels of the L-type. It was similar in the pulmonary artery and in the human renal and right coronary arteries. Light microscope autoradiogr aphy revealed a high density of [H-3]-nicardipine binding sites within smooth muscle of the tunica media of human pulmonary artery as well a s of human renal and right coronary arteries. A lower accumulation of the radioligand occurred in the tunica adventitia. No specific binding was noticeable in the tunica intima. Our data suggest that human pulm onary artery expresses Ca2+ channels of the L-type sensitive to dihydr opyridines. These sites have similar affinity and lower density than t hose expressed by systemic arteries. The presence of Ca2+ channels of the L-type in human pulmonary artery suggests that their pharmacologic al manipulation may be considered in the treatment of pulmonary hypert ension.