AGT and substance dependence: Previous studies in both cultured thick ascending loop of Henle (TALH) cells and in transgenic mice specifically overexpressing HO-1 in the TALH have demonstrated that HO-1 can protect against Ang II-mediated increases in ROS production, decrease the levels of the sodium-potassium 2 chloride (NKCC2) transporter, and attenuate the development of Ang II-dependent hypertension [28,31].