Effects of nifedipine-induced pulmonary vasodilatation on cardiac receptors and protein kinase C isoforms in the chronically hypoxic rat.

Abstract

In chronic hypoxia, pulmonary hypertension induces a right ventricular (RV) hypertrophy (RVH) and the catecholamine-activated adrenergic system modulates cardiovascular responses through alpha- and beta-adrenergic pathways. The alpha(1)-adrenergic receptor (alpha(1)-AR) and protein kinase C (PKC) may play an important role in the signaling pathway leading to RVH. The aim of this study was to examine the relationship between nifedipine-induced pulmonary vasodilatation, the blunting of RVH and the modifications in the density of alpha(1)-AR, PKC activity and expression of PKC isoforms. In rats exposed to 15 days of hypoxia (380 torr, 50.66 kPa), RV pressure increased and RVH developed. Nifedipine, a calcium antagonist, given through gastric administration, partially decreased RV pressure and RVH. In both ventricles, hypoxia decreased alpha(1)-AR and beta-AR density and increased muscarinic acetylcholine receptor density. Nifedipine decreased alpha(1)-AR density only in normoxia. Expression of epsilon, delta and zeta PKC isoforms increased with RVH and normalized with nifedipine treatment. In conclusion, in this in vivo model of hypoxic rat, no relation was found between a RVH decrease and cardiac receptor densities. However, the development and regression of pulmonary hypertension and RVH were related to the expression of some PKC isoforms suggesting that pathways other than alpha(1)-AR might be involved in hypoxia-induced ventricular hypertrophy.