Artery‐specific gene expression changes following chronic L‐NAME administration in Yucatan miniswine

Abstract

Nitric oxide (NO) is an important vasodilator and signaling molecule in the arterial tree. The bioavailability of NO is dependent in part upon its production and interaction with other reactive oxygen species (ROS). We sought to examine select gene expression changes following systemic administration (30 d) of the nitric oxide synthase (NOS) inhibitor L‐NAME (8.0 mg/kg/d) in Yucatan miniswine (~30 kg). After sacrifice ~1 cm segments of the right coronary and femoral arteries were dissected, cleaned and stripped of endothelial cells. Total RNA from smooth muscle and endothelial cells was isolated and 1 ug was used for cDNA synthesis using random primers. Real time PCR (SYBR green) was performed using primers specific for endothelial NOS (eNOS), gp22phox and catalase with 18S rRNA used for normalization. Results suggested that within endothelial cells gene expression was higher in the femoral than in the coronary artery. In coronary endothelial cells, L‐NAME administration tended to increase catalase gene expression while eNOS and gp22phox appeared relatively unchanged. In contrast, L‐NAME tended to decrease all gene expression in femoral artery endothelial cells. The data suggest that regional differences along the arterial tree exist in relation to NO and ROS production between control and NOS‐inhibited states. These apparent differences may be in response to differences in shear stress along the arterial tree.