On the relation of nitric oxide to nifedipine-induced gingival hyperplasia and impaired submandibular glands function in rats in vivo.
Calcium-channel blockers such as nifedipine could be associated with gingival overgrowth. The aim of this study was to examine the role of nitric oxide (NO) on nifedipine-induced gingival hyperplasia along with submandibular secretory function in rats. Animals in divided groups received nifedipine (250 mg/kg diet) alone and in combination with L-arginine (2.25% w/v) or N(omega)-nitro-L-arginine methyl ester (L-NAME) (0.7% w/v) in drinking water for 20 days. Controls received only tap water. Pure submandibular saliva was collected intraorally by micropolyethylene cannula and the mandibular gingiva was examined by means of dissecting microscope for signs of redness, thickness, inflammation and exuda. Twenty-day nifedipine treatment induced gingival hyperplasia accompanied with reduced salivary flow rate and concentrations of total protein, epidermal growth factor (EGF) and calcium in comparison with controls. Co-treatment of animals with nifedipine and L-arginine protected from gingival hyperplasia and retained flow rate, and concentrations of total protein, EGF and calcium in normal levels. Co-treatment of animals with nifedipine and L-NAME potentiated nifedipine-induced gingival hyperplasia and reductions in flow rate and concentrations of total protein, EGF, and calcium. It is concluded that nifedipine-induced gingival hyperplasia is associated with salivary dysfunction. Activation of cGMP-dependent positive signal-transduction mechanisms in salivary glands might be the mechanism for protective effects of NO against nifedipine-induced gingival hyperplasia.
Rezaie
Shourangiz
S
Laboratory of Toxicology, Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Rezaie
Ali
A
Minaiee
Bagher
B
Khorasani
Reza
R
Abdollahi
Mohammad
M
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000009:adverse effects*; D004815:Epidermal Growth Factor / Q000378:metabolism; D005885:Gingival Hyperplasia / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009543:Nifedipine / Q000009:adverse effects*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012463:Saliva / Q000378:metabolism / Q000502:physiology; D012471:Salivary Proteins and Peptides / Q000378:metabolism; D013363:Submandibular Gland / Q000378:metabolism*
D002121:Calcium Channel Blockers; D012471:Salivary Proteins and Peptides; D009569:Nitric Oxide; D004815:Epidermal Growth Factor; D001120:Arginine; D019001:Nitric Oxide Synthase; D009543:Nifedipine; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester