The effect of chloroquine on the TRPC1, TRPC6, and CaSR in the pulmonary artery smooth muscle cells in hypoxia-induced experimental pulmonary artery hypertension


KAYMAK E. , AKİN A. T. , Tufan E., BAŞARAN K. E. , TAHERİ S., Ozdamar S., ...More

JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, vol.35, no.2, 2021 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 35 Issue: 2
  • Publication Date: 2021
  • Doi Number: 10.1002/jbt.22636
  • Title of Journal : JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY
  • Keywords: calcium channel, chloroquine, hypertension, hypoxia, CALCIUM-SENSING RECEPTOR, OPERATED CA2+ CHANNELS, NA+/CA2+ EXCHANGER, UP-REGULATION, ENTRY, VENTILATION, INHIBITION, ACCLIMATIZATION, CIRCULATION, HOMEOSTASIS

Abstract

Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by a constant high pulmonary artery pressure and the remodeling of the vessel. Chloroquine (CLQ) has been observed to inhibit calcium influx. The aim of this study is to investigate the effect of CLQ on transient receptor cationic proteins (TRPC1 and TRPC6) and extracellular calcium-sensitive receptor (CaSR) in a hypoxic PAH model. In this study, 8- to 12-week-old 32 male Wistar albino rats, weighing 200 to 300 g, were used. The rats were studied in four groups, including normoxy control, n = 8; normoxy CLQ (50 mg/kg/28 d), n = 8; hypoxia (HX; 10% oxygen/28 d) control, n = 8; and HX (10% oxygen/28 d) + CLQ (50 mg/kg), N = 8. Pulmonary arterial medial wall thickness, pulmonary arteriole wall, TRPC1, TRPC6, and CaSR expressions were evaluated by immunohistochemistry, polymerase chain reaction, and enzyme-linked immunosorbent assay methods. At the end of the experiment, a statistically significant increase in the medial wall thickness was observed in the hypoxic group as compared with the control group. However, in the HX + CLQ group, there was a statistically significant decrease in the vessel medial wall as compared with the HX group. In the TRPC1-, TRPC6-, and CaSR-immunopositive cell numbers, messenger RNA expressions and biochemical results showed an increase in the HX group, whereas they were decreased in the HX + CLQ group. The inhibitory effect of CLQ on calcium receptors in arterioles was observed in PAH.