Sodium nitroprusside attenuates hyperproliferation of vascular smooth muscle cells from spontaneously hypertensive rats through the inhibition of overexpression of AT1 receptor, cell cycle proteins and c-Src/growth factor receptor signaling pathways.

Sodium nitroprusside attenuates hyperproliferation of vascular smooth muscle cells from spontaneously hypertensive rats through the inhibition of overexpression of AT1 receptor, cell cycle proteins and c-Src/growth factor receptor signaling pathways. Can J Physiol Pharmacol. 2019 Oct 02;: Authors: Hossain E, Sarkar O, Li Y, Anand-Srivastava MB Abstract We recently showed that sodium nitroprusside (SNP), an NO donor, attenuated hypertension in spontaneously hypertensive rats (SHR). Since hypertension is associated with enhanced prolifera-tion and hypertrophy of vascular smooth muscle cells (VSMC), the present study examines whether in vivo treatment of SHR with SNP could also inhibit the augmented proliferation of VSMC and explore the signaling mechanisms. Treatment of 8-week-old SHR and WKY rats with SNP twice a week for two weeks inhibited the enhanced proliferation of VSMC from SHR, the enhanced expression of AT1 receptor, enhanced activation of c-Src, growth factor receptors and ERK1/2 signaling pathways. In addition, SNP also inhibited the overexpression of cell cycle pro-teins including cyclins D1, Cdk4, phosphorylated pRB and restored the downregulated Cdk inhibitors, p21Cip1 and p27Kip1expression towards control levels. Furthermore, SNP-induced inhibition of enhanced levels of AT1 receptor and enhanced proliferation was reversed by L-NAME, an inhibitor of nitric oxide synthase. These results suggest that SNP-induced antiprolif...
Source: Canadian Journal of Physiology and Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Can J Physiol Pharmacol Source Type: research