Effects of angiotensin-converting enzyme inhibitor and α1- adrenoceptor antagonist on hypertension induced in rats by long- term inhibition of nitric oxide production

Background: We aimed to elucidate the involvement of the renin-angiotensin system (RAS) and sympathetic nervous system in hypertension induced by the long-term inhibition of nitric oxide (NO) production. Methods: We compared the effects of 9-week treatment with an angiotensin-converting enzyme inhibitor (ACEI), cilazapril (10 mg/kg per day), to that with an α1-adrenoceptor antagonist, doxazosin (10 mg/kg per day), on systemic blood pressure and renal histological changes in Sprague-Dawley rats continuously treated with oral N(G)nitro-L-arginine (L-NA). Results: L-NA induced renal damage associated with a significant fall in urinary nitrate and nitrite (NOx) excretion and a significant rise in systolic blood pressure. Although cilazapril and doxazosin restored urinary NOx to a similar level, only cilazapril treatment significantly suppressed the hypertensive effect of L-NA. Urinary protein excretion in L-NA-treated rats was also significantly reduced by cilazapril treatment. Histologically, treatment with cilazapril, but not doxazosin, significantly inhibited the glomerular injury of mesangial expansion and glomerular sclerosis induced by L-NA treatment. Furthermore, cilazapril significantly reduced urinary aldosterone level. Conclusion: Our findings indicate that the hypertension and hypertensive glomerular injury induced by long-term L-NA treatment were abrogated by an ACEI but not by an α1- adrenoceptor antagonist, and that the fall in high blood pressure induced by treatment with the ACEI was independent of urinary NOx excretion in this model.