Key result
Combination therapy with valsartan and cilnidipine significantly reduced systolic blood pressure and provided superior vascular protection via attenuation of oxidative stress compared to valsartan alone or valsartan plus amlodipine in hypertensive rats.
Why the study?
Does combining cilnidipine with valsartan improve vascular protection compared to valsartan alone or valsartan plus amlodipine in stroke-prone spontaneously hypertensive rats?
Does combining cilnidipine with valsartan improve vascular protection compared to valsartan alone or valsartan plus amlodipine in stroke-prone spontaneously hypertensive rats?
Combining the L/N-type CCB cilnidipine with valsartan provides superior vascular protection and oxidative stress reduction compared to valsartan alone or valsartan plus amlodipine in a hypertensive rat model.
Answers are grounded in this paper and cite their sources.
Hypothesis-generating for cilnidipine-valsartan vascular effects; leaves open translation to human hypertension.
Cilnidipine is an L- and N-type calcium channel blocker (CCB), and amlodipine is an L-type CCB. Valsartan (10 mg kg(-1)), valsartan (10 mg kg(-1)) and amlodipine (1 mg kg(-1)), and valsartan (10 mg kg(-1)) and cilnidipine (1 mg kg(-1)) were administered once daily for 2 weeks to stroke-prone, spontaneously hypertensive rats (SHR-SPs). Blood pressure was significantly reduced by valsartan, and it was further reduced by the combination therapies. Vascular endothelial dysfunction was significantly attenuated in all therapeutic groups, and further significant attenuation was observed in the valsartan+cilnidipine-treated group, but not in the valsartan+amlodipine-treated group. Vascular nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit NOX1 gene expression was significantly attenuated in all therapeutic groups, and significantly greater attenuation was observed in the valsartan+cilnidipine-treated group than in the valsartan-treated group. Compared with the valsartan-treated group, the positive areas for 4-hydroxy-2-nonenal were significantly lower only in the valsartan+cilnidipine-treated group. Plasma renin activity was significantly augmented in the valsartan-treated group, and it was significantly attenuated in the valsartan+cilnidipine-treated group. A significant increase in the ratio of plasma angiotensin-(1-7) to angiotensin II was observed only in the valsartan+cilnidipine-treated group. Vascular angiotensin-converting enzyme (ACE) gene expression was significantly attenuated only in the valsartan+cilnidipine-treated group, but ACE2 gene expression was significantly higher in all of the therapeutic groups. Thus, valsartan and cilnidipine combination therapy might have a powerful protective effect in the vascular tissues via increases in the angiotensin-(1-7)/angiotensin II ratio in plasma.
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Takai et al. (2012) studied Hypertension (stroke-prone spontaneously hypertensive rats) (n=30). Valsartan and cilnidipine combination therapy vs. Placebo, valsartan monotherapy, or valsartan + amlodipine was evaluated on Systolic blood pressure at 2 weeks (mmHg) (p=<0.01). Combination therapy with valsartan and cilnidipine significantly reduced systolic blood pressure and provided superior vascular protection via attenuation of oxidative stress compared to valsartan alone or valsartan plus amlodipine in hypertensive rats.
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