Influence of age on L-type Ca2+ channels in the pulmonary artery and vein of spontaneously hypertensive rats

The influence of age on the density and localization of L-type Ca2+ channel s was studied during development of hypertension in the pulmonary artery an d vein of spontaneously hypertensive rats (SHR) and age-matched normotensiv e Wistar-Kyoto (WKY) rats by radioligand binding assay and light microscope autoradiography. SHR were examined at 6 weeks (juvenile, pre-hypertensive stage), 12 weeks (young, developing hypertension) and 24 weeks (mature, est ablished hypertension). The dihydropyridine-type Ca2+ antagonist [H-3]nicar dipine was used as a radioligand. It was bound specifically to sections of rat pulmonary artery and vein. Dissociation constant (K-d) values were simi lar in WKY rats and SHR, whereas maximum density of binding sites (B-max) v alues increased in SHR in comparison with WKY rats. This increase was notic eable from the pre-hypertensive phase. The pharmacological profile of [H-3] nicardipine binding was similar in different age groups of either normotens ive and hypertensive rats. Quantitative analysis of autoradiographs from SH R revealed a progressive increase of silver grains in smooth muscle of tuni ca media and to a lesser extent in the adventitia of pulmonary artery but n ot of pulmonary Vein from pre-hypertensive stage to developing hypertension . No further changes were observed in established hypertension. The above d ata indicate that the density of L-type Ca2+ channels of pulmonary arteries is increased in SHR. This augmentation after the pre-hypertensive phase su ggests the occurrence of dysregulation of Ca2+ handling in the pulmonary va sculature of developing SHR. (C) 2000 Elsevier Science Ireland Ltd. All rig hts reserved.