Influence of age on L-type Ca 2+ channels in the pulmonary artery and vein of spontaneously hypertensive rats

Abstract

The influence of age on the density and localization of L-type Ca 2+ channels was studied during development of hypertension in the pulmonary artery and vein of spontaneously hypertensive rats (SHR) and age-matched normotensive 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, established hypertension). The dihydropyridine-type Ca 2+ antagonist [ 3H]nicardipine was used as a radioligand. It was bound specifically to sections of rat pulmonary artery and vein. Dissociation constant ( K d) values were similar in WKY rats and SHR, whereas maximum density of binding sites ( B max) values increased in SHR in comparison with WKY rats. This increase was noticeable from the pre-hypertensive phase. The pharmacological profile of [ 3H]nicardipine binding was similar in different age groups of either normotensive and hypertensive rats. Quantitative analysis of autoradiographs from SHR revealed a progressive increase of silver grains in smooth muscle of tunica media and to a lesser extent in the adventitia of pulmonary artery but not of pulmonary vein from pre-hypertensive stage to developing hypertension. No further changes were observed in established hypertension. The above data indicate that the density of L-type Ca 2+ channels of pulmonary arteries is increased in SHR. This augmentation after the pre-hypertensive phase suggests the occurrence of dysregulation of Ca 2+ handling in the pulmonary vasculature of developing SHR.