lacidipine and Inflammation

This study was performed to evaluate the possible protective effect of two calcium channel blocker's "lacidipine (LAC) and amlodipine (AML)" on bone metabolism in an experimental ovariectomized and inflammation-induced osteoporosis rat model (OVXinf). For the purpose of this study, the rats were divided into eight groups, each containing eight rats: sham-operated control (group 1, SH), sham + inflammation (group 2, SHinf), ovariectomy (group 3, OVX), ovariectomy + inflammation (group 4, OVXinf), ovariectomy + LAC 4 mg/kg (group 5, OVX + LAC), ovariectomy + inflammation + LAC 4 mg/kg (group 6, OVXinf + LAC), ovariectomy + AML 5 mg/kg (group 7, OVX + AML), ovariectomy + inflammation + AML 5 mg/kg (group 8, OVXinf + AML). The levels of osteocalcin and osteopontin decreased in OVXinf + LAC and OVXinf + AML groups. The serum levels of TNF-α, IL-1β, and IL-6 were increased significantly in the OVXinf rats compared with the SH group. Gene expression levels of the osteogenic factor runt-related transcription factor 2 (Runx2) and type I collagen 1A1 (Col1A1) significantly decreased in the OVXinf group, when compared with the control group. AML or LAC administrations increased the levels of Runx2 and Col1A1. These results suggest that amlodipine and lacidipine may be a novel therapeutic target for radical osteoporosis treatment in hypertensive patients.

Topics: Amlodipine; Animals; Bone Density; Calcium Channel Blockers; Collagen Type I; Collagen Type I, alpha 1 Chain; Core Binding Factor Alpha 1 Subunit; Dihydropyridines; Female; Humans; Hypertension; Inflammation; Interleukin-1beta; Interleukin-6; Osteocalcin; Osteopontin; Osteoporosis; Ovariectomy; Rats; Rats, Wistar; Tumor Necrosis Factor-alpha

Inflammation and increased capillary permeability is a significant aspect of the pathogenesis of many diseases including atherosclerosis. L-type calcium channel blockers (CCB) are commonly used as cardiovascular drugs. Amlodipine, lacidipine, and nicardipine were evaluated for anti-inflammatory activity on the paw oedema produced by carrageenan. The effect of these drugs was compared with the activity of indomethacin. Their effects on vascular permeability were also tested by hyaluronidase-induced capillary permeability. In our animal experiments, amlodipine decreased the carrageenan-induced paw oedema at doses of 1, 3, and 6 mg kg(-1) by 27.3%, 43.7%, and 67.3% four hour after carrageenan administration; the same doses of lacidipine and nicardipine decreased paw oedema by 37.1%, 55.6%, 76.4%, 11.2%, 31.0%, 91%; and indomethacin decreased oedema by 38.2% at a dose of 6 mg kg(-1). Lacidipine significantly inhibited the hyaluronidase-induced increase in capillary permeability at doses of 1, 3, and 6 mg kg(-1) compared with the control group. However, amlodipine and nicardipine significantly inhibited the hyaluronidase-induced increase in capillary permeability at 3 and 6 mg kg(-1) doses. A 6 mg kg(-1) dose of indomethacin significantly decreased the capillary permeability which was increased by hyaluronidase. These results suggest that CCBs can be efficient anti-inflammatories, and can also significantly decrease capillary permeability.

Topics: Amlodipine; Animals; Calcium Channel Blockers; Capillary Permeability; Carrageenan; Dihydropyridines; Hyaluronoglucosaminidase; Inflammation; Injections, Intravenous; Male; Nicardipine; Rats; Rats, Wistar