Anti-atrial Fibrillatory and Cardiorenal Protective Effects of the Combination of Valsartan and Cilnidipine in Dahl Salt-Sensitive Rats

• Published in: Biological & pharmaceutical bulletin Vol. 47; no. 7; pp. 1360 - 1367
• Main Authors: Harada, Eri, Sugino, Kazumi, Takahara, Akira
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 30-07-2024; Japan Science and Technology Agency
• Subjects: Amlodipine - pharmacology; Animals; atrial fibrillation; Atrial Fibrillation - drug therapy; Blood pressure; Blood Pressure - drug effects; Calcium (urinary); Calcium Channel Blockers - pharmacology; cardiac remodeling; Cilnidipine; combination therapy; Dihydropyridines - pharmacology; Drug Therapy, Combination; Echocardiography; Heart; Heart Atria - drug effects; Kidney - drug effects; Male; N-type Ca2+ channel; Oral administration; Rats; Rats, Inbred Dahl; Renal function; valsartan; Valsartan - pharmacology; Ventricle; Ventricular Function, Left - drug effects; cilnidipine; combination therapy; valsartan; atrial fibrillation; N-type Ca2+ channel; cardiac remodeling
• ISSN: 0918-6158; 1347-5215; 1347-5215
• DOI: 10.1248/bpb.b24-00265

The current study aimed to investigate the anti-atrial fibrillatory (AF) effects of a combination of valsartan and a calcium channel blocker (cilnidipine or amlodipine) in Dahl salt-sensitive (Dahl S) rats. Seven-week-old male Dahl S rats were fed an 8% salt diet. Six weeks later, valsartan (60 mg/kg, Val group), cilnidipine + valsartan (10 + 60 mg/kg, CV group), amlodipine + valsartan (3 + 60 mg/kg, AV group), or vehicle was orally administered daily for 5 weeks. Echocardiography and atrial electrophysiological evaluations were performed on the last day of treatment. Blood pressure in each drug treatment group was lower than in the Vehicle group. The duration of AF induced by atrial burst stimulation was shorter in the Val group (3.2 ± 1.6 s) than in the Vehicle group (11.2 ± 6.0 s), which was further shortened in the CV and AV groups (1.1 ± 0.3 and 1.3 ± 0.3 s, respectively). Left ventricular ejection fraction and left ventricular fractional shortening were greater in the CV and AV groups than those in the Vehicle group. Urinary albumin excretion in the CV group was the lowest among the drug-treated groups. The results collectively suggest that the combination of a calcium channel blocker with valsartan could be useful in terms of its anti-AF action as well as for improving cardiac and renal functions.