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

In chronic hypoxia, pulmonary hypertension induces a right ventricular (RV) hypertrophy (RVH) and the catecholamine-activated adrenergic system modulates cardiovascular responses through α- and β-adrenergic pathways. The α₁-adrenergic receptor (α₁-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 α₁-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 α₁-AR and β-AR density and increased muscarinic acetylcholine receptor density. Nifedipine decreased α₁-AR density only in normoxia. Expression of ε, δ and ζ 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 α₁-AR might be involved in hypoxia-induced ventricular hypertrophy.