Cilnidipine Lowers Plasma Leptin of Patients with Obese Hypertension Associated with Cerebrovascular Disorder

Abstract

Background: Since cilnidipine suppresses not only the L-type but also N-type calcium channels found on peripheral sympathetic nerve endings which control noradrenaline release, it is thought to be a Ca antagonist with low sympathetic nerve activation when lowering blood pressure (dual blocking action). As activation of sympathetic nervous system is suggested to contribute to hypertension in obesity, dual blocking action of cilnidipine may contribute to patients with obesity-hypertension. Methods: The effects of cilnidipine on plasma leptin levels and blood pressure were studied. Twenty three patients with obesity-hypertension associated with a past history of stroke or ischemic changes confirmed by brain magnetic resonance imaging were enrolled. Cilnidipine (10 mg/day) was administered orally once a day after breakfast. The duration of the study treatment was 12 weeks. Retroperitoneal adipose tissues around the kidney of both fat and lean cadaver and neuronal and non-neuronal tissues of rat were used for immunohistochemical examination. Result: The mean circulating leptin level decreased from 11.8 ng/ml to 10.8 ng/ml that reached statistical significance. Multiple regression analysis revealed no significant effects of covariates except for baseline leptin level. An immunohistochemical study revealed that N-type calcium channel protein was expressed on the cell membrane of adipocytes. We speculate that a blockade of calcium current through the N-type channel, instead of the L-type channel may suppress leptin secretion. Conclusion: The dual blocking action of cilnidipine may help control both arterial hypertension and leptininduced atherosclerosis in patients with obese hypertension associated with cerebrovascular disorder.