Abstract
Background: Excessive urinary albumin excretion is associated with hypertension and diabetic nephropathy. Calcium channel blockers (CCBs) used as antihypertensives suppress such albuminuria with variable efficacy. While hypertension benefits from the addition of angiotensin receptor blockers (ARBs), it is unknown if ARBs alter the effects of CCBs on albuminuria. Objective: This study compared the efficacy of combined ARB irbesartan with either CCB amlodipine or CCB cilnidipine on albuminuria associated with experimental diabetic nephropathy. Methods: Male Sprague-Dawley rats with streptozotocin-induced diabetes were treated with a CCB alone (amlodipine 2.0 mg/kg/d or cilnidipine 2.0 mg/kg/d), an ARB alone (irbesartan 20.0 mg/kg/d), or combinations. In the acute protocol, changes in glomerular afferent and efferent arteriole diameters were examined by a charge-coupled device video microscope following single doses. In the chronic protocol, urinary albumin excretion, glomerular reactive oxygen species, and endothelial surface layer (ESL) condition were evaluated after 2 weeks of daily treatment. Results: In the acute protocol, cilnidipine mono therapy caused a greater dilation in glomerular efferent arterioles than amlodipine monotherapy, while combination therapy with irbesartan induced comparable efferent arteriole dilation. In the chronic protocol, cilnidipine mono therapy suppressed albuminuria, reduced glomerular oxidative stress, and protected the glomerular ESL against degeneration to a much greater extent that amlodipine monotherapy. However, addition of irbesartan reduced albumin excretion, oxidative stress, and ESL degeneration to the same extent in both groups. Conclusions: While cilnidipine is more effective alone, the combinations of irbesartan with cilnidipine or amlodipine are equally effective for reducing albuminuria and other pathological sequela of experimental diabetic nephropathy.
Highlights
Managing hypertension is important for reducing the risks of cardiovascular and renal diseases [1,2]
In the acute protocol, cilnidipine mono therapy caused a greater dilation in glomerular efferent arterioles than amlodipine monotherapy, while combination therapy with irbesartan induced comparable efferent arteriole dilation
While cilnidipine is more effective alone, the combinations of irbesartan with cilnidipine or amlodipine are effective for reducing albuminuria and other pathological sequela of experimental diabetic nephropathy
Summary
Managing hypertension is important for reducing the risks of cardiovascular and renal diseases [1,2]. Renin angiotensin system (RAS) inhibitors are recommended for cardiovascular or chronic kidney disease [3]; it can be difficult to achieve the recommended target blood pressure (
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
