Effect of 7-nitroindazole on the expression of intracellular calcium channels in the kidney of spontaneously hypertensive rats

Gen Physiol Biophys. 2009 Sep;28(3):225-32. doi: 10.4149/gpb_2009_03_225.

Abstract

The spontaneously hypertensive rats (SHR) were fed with nitric oxide synthase (NOS) blocker 7-nitroindazole (7-NI, 10 mg/kg/day) for 6 weeks and an expression of intracellular calcium channels, SERCA and proapoptotic agents was evaluated in kidney. Treatment of rats with 7-NI resulted in a significant increase in mRNA and protein levels of the IP3 receptors type 1 and type 2, while mRNA levels of the IP3 receptor type 3 remained unchanged. The mRNA of other intracellular calcium channels, ryanodine receptors type 1 and type 2 was also upregulated by 7-NI treatment. Gene expression of the SERCA2a, calcium pump responsible for loading intracellular stores with calcium, revealed increased gene expression due to 7-NI as well. Interestingly, proapoptotic agents caspase 3 and Bax were also upregulated by the 7-NI treatment. These results may indicate that nNOS blocker 7-NI modifies intracellular calcium transport system, which may have impact on altered calcium handling and regulation of various metabolic pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium Channels / genetics
  • Calcium Channels / metabolism*
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Enzyme Inhibitors / pharmacology*
  • Gene Expression / drug effects
  • Indazoles / pharmacology*
  • Inositol 1,4,5-Trisphosphate Receptors / genetics
  • Inositol 1,4,5-Trisphosphate Receptors / metabolism
  • Intracellular Space / drug effects*
  • Intracellular Space / metabolism
  • Kidney / drug effects*
  • Kidney / metabolism
  • Male
  • Nitric Oxide Synthase / antagonists & inhibitors
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Inbred SHR
  • Ryanodine Receptor Calcium Release Channel / genetics
  • Ryanodine Receptor Calcium Release Channel / metabolism
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases / genetics
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases / metabolism
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism

Substances

  • Bax protein, rat
  • Calcium Channels
  • Enzyme Inhibitors
  • Indazoles
  • Inositol 1,4,5-Trisphosphate Receptors
  • RNA, Messenger
  • Ryanodine Receptor Calcium Release Channel
  • bcl-2-Associated X Protein
  • Nitric Oxide Synthase
  • Casp3 protein, rat
  • Caspase 3
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases
  • 7-nitroindazole