Abstract-There is substantial evidence suggesting that angiotensin II plays an important role in elevating blood pressure of spontaneously hypertensive rats, despite normal plasma renin activity, and that converting enzyme inhibitors (captopril) can effectively normalize blood pressure in the spontaneously hypertensive rats. One mechanism by which angiotensin II induces hypertension is via oxidative stress and endothelin, as seen in subpressor angiotensin II-induced hypertension. In fact, it has been shown that antioxidants lower mean arterial pressure in spontaneously hypertensive rats. However, the relationship between angiotensin II, oxidative stress, and endothelin in the spontaneously hypertensive rats is still relatively undefined. This study examines the relationship between mean arterial pressure, plasma renin activity, angiotensin II, oxidative stress, and endothelin in spontaneously hypertensive rats compared with normotensive Wistar Kyoto rats, and the effects of captopril on this association. Untreated spontaneously hypertensive rats had increased plasma angiotensin II levels despite normal plasma renin activity, oxidative stress, and endothelin. Captopril treatment in spontaneously hypertensive rats lowered mean arterial pressure, angiotensin II, oxidative stress, and endothelin, and increased plasma renin activity. In contrast, captopril increased plasma renin activity (suggesting effective captopril treatment) but did not significantly alter mean arterial pressure, angiotensin II, oxidative stress, or endothelin of Wistar Kyoto rats. These results suggest that in spontaneously hypertensive rats, angiotensin II is a primary instigator of hypertension, and that captopril selectively lowers angiotensin II, oxidant stress, and endothelin, which in turn may contribute to the blood pressure-lowering efficacy of captopril in spontaneously hypertensive rats. Key Words: angiotensin II Ⅲ angiotensin-converting enzyme inhibitors Ⅲ captopril Ⅲ endothelin Ⅲ oxidative stress Ⅲ rats, spontaneously hypertensive N umerous studies have been performed to define the regulatory factors that participate in the pathogenesis of hypertension in spontaneously hypertensive rats (SHR). These studies have demonstrated that despite the presence of normal plasma renin activity (PRA), angiotensin II (Ang II) still appears to play a key role in the pathogenesis of the increased blood pressure. Blood pressure is normalized by administrating renin inhibitors, 1 converting enzyme inhibitors, 2,3 or Ang II receptor blockers. 4 -6 However, despite the efficacy of these agents in lowering blood pressure, the mechanisms that lead to the Ang II-dependent increase in blood pressure in the SHR remain undefined.One mechanism by which Ang II can induce hypertension is via oxidative stress and endothelin (ET). This pathway has been shown to be essential in the maintenance of blood pressure in several models of Ang II-dependent hypertension, including subpressor Ang II-induced hypertension [7][8][9][10][11] and 1-kidney Goldblatt hypertension...

Background: Tissue regeneration is a complex process involving a network of ligand-activated pathways. Results:The sulfatase SULF2 modulates cell proliferation and organ growth through a WNT-dependent activation of the transcription factor GLI1. Conclusion: Together, these data define a novel cascade regulating tissue regeneration. Significance: The knowledge derived from this study will contribute to the understanding of the molecular mechanisms modulating regeneration and organogenesis.