Felodipine is a calcium channel blocker that is used in the management of hypertension. Calcium channel blockers, along with phenytoin and cyclosporin, are implicated as a cause of gingival hyperplasia. Calcium channel blockers associated with this undesired side-effect include nifedipine, nicardipine, isradipine, amlodipine, felodipine, verapamil, and diltiazem. Several cases of adverse gingival hyperplasia related to felodipine have been reported since 1991, although no case has been reported in Korea. We report a case of gingival hyperplasia in a 55-year-old man on long-term felodipine.
Amlodipine ; Calcium Channel Blockers ; Calcium Channels ; Cyclosporine ; Diltiazem ; Felodipine ; Gingival Hyperplasia ; Humans ; Hypertension ; Isradipine ; Korea ; Middle Aged ; Nicardipine ; Nifedipine ; Phenytoin ; Verapamil

The present study was attempted to investigate whether polyphenolic compounds isolated from wine, which is brewed from Rubus coreanum Miquel (PCRC), may affect the release of catecholamines (CA) from the isolated perfused adrenal medulla of the spontaneously hypertensive rats (SHRs), and to establish its mechanism of action. PCRC (20~180 microgram/ml) perfused into an adrenal vein for 90 min relatively dose-dependently inhibited the CA secretory responses to ACh (5.32 mM), high K+ (56 mM), DMPP (100 micrometer) and McN-A-343 (100 micrometer). PCRC itself did not affect basal CA secretion (data not shown). Also, in the presence of PCRC (60 microgram/ml), the CA secretory responses to veratridine (a selective Na+ channel activator (10 micrometer), Bay-K-8644 (a L-type dihydropyridine Ca2+ channel activator, 10 micrometer), and cyclopiazonic acid (a cytoplasmic Ca2+ -ATPase inhibitor, 10 micrometer) were significantly reduced, respectively. In the simultaneous presence of PCRC (60 microgram/ml) and L-NAME (an inhibitor of NO synthase, 30 micrometer), the inhibitory responses of PCRC on the CA secretion evoked by ACh, high K+, DMPP, and Bay-K-8644 were considerably recovered to the extent of the corresponding control secretion compared with that of PCRC-treatment alone. The level of NO released from adrenal medulla after the treatment of PCRC (60 microgram/ml) was greatly elevated compared with the corresponding basal level. Taken together, these results demonstrate that PCRC inhibits the CA secretion from the isolated perfused adrenal medulla of the SHRs evoked by stimulation of cholinergic receptors as well as by direct membrane-depolarization. It seems that this inhibitory effect of PCRC is mediated by blocking the influx of calcium and sodium into the adrenal medullary chromaffin cells of the SHRs as well as by inhibition of Ca2+ release from the cytoplasmic calcium store at least partly through the increased NO production due to the activation of NO synthase.
(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride ; 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester ; Adrenal Medulla ; Calcium ; Catecholamines ; Chromaffin Cells ; Cytoplasm ; Dihydropyridines ; Dimethylphenylpiperazinium Iodide ; Indoles ; NG-Nitroarginine Methyl Ester ; Nitric Oxide ; Nitric Oxide Synthase ; Polyphenols ; Rats, Inbred SHR ; Receptors, Cholinergic ; Sodium ; Veins ; Veratridine ; Wine

Resveratrol has been known to possess various potent cardiovascular effects in animal, but there is little information on its functional effect on the secretion of catecholamines (CA) from the perfused model of the adrenal medulla. Therefore, the aim of the present study was to determine the effect of resveratrol on the CA secretion from the isolated perfused model of the normotensive rat adrenal gland, and to elucidate its mechanism of action. Resveratrol (10~100micrometer) during perfusion into an adrenal vein for 90 min inhibited the CA secretory responses evoked by ACh (5.32 mM), high K+ (a direct membrane-depolarizer, 56 mM), DMPP (a selective neuronal nicotinic Nn receptor agonist, 100micrometer) and McN-A-343 (a selective muscarinic M1 receptor agonist, 100micrometer) in both a time- and dose- dependent fashion. Also, in the presence of resveratrol (30micrometer), the secretory responses of CA evoked by veratridine 8644 (an activator of voltage-dependent Na+ channels, 100micrometer), Bay-K-8644 (a L-type dihydropyridine Ca2+ channel activator, 10micrometer), and cyclopiazonic acid (a cytoplasmic Ca2+ -ATPase inhibitor, 10micrometer) were significantly reduced. In the simultaneous presence of resveratrol (30micrometer) and L-NAME (an inhibitor of NO synthase, 30micrometer), the CA secretory evoked by ACh, high K+, DMPP, McN-A-343, Bay-K-8644 and cyclopiazonic acid were recovered to a considerable extent of the corresponding control secretion compared with the inhibitory effect of resveratrol alone. Interestingly, the amount of nitric oxide (NO) released from the adrenal medulla was greatly increased in comparison to its basal release. Taken together, these experimental results demonstrate that resveratrol can inhibit the CA secretory responses evoked by stimulation of cholinergic nicotinic receptors, as well as by direct membrane-depolarization in the isolated perfused model of the rat adrenal gland. It seems that this inhibitory effect of resveratrol is exerted by inhibiting an influx of both ions through Na+ and Ca2+ channels into the adrenomedullary cells as well as by blocking the release of Ca2+ from the cytoplasmic calcium store, which are mediated at least partly by the increased NO production due to the activation of NO synthase.
(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride ; 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester ; Adrenal Glands ; Adrenal Medulla ; Animals ; Calcium ; Catecholamines ; Cytoplasm ; Dihydropyridines ; Dimethylphenylpiperazinium Iodide ; Indoles ; Ions ; Neurons ; NG-Nitroarginine Methyl Ester ; Nitric Oxide ; Nitric Oxide Synthase ; Perfusion ; Rats ; Receptor, Muscarinic M1 ; Receptors, Cholinergic ; Receptors, Nicotinic ; Stilbenes ; Veins ; Veratridine

The aim of the present study was to examine the effect of provinol, which is a mixture of polyphenolic compounds from red wine, on the secretion of catecholamines (CA) from isolated perfused rat adrenal medulla, and to elucidate its mechanism of action. Provinol (0.3~3 microgram/ml) perfused into an adrenal vein for 90 min dose- and time-dependently inhibited the CA secretory responses evoked by ACh (5.32 mM), high K+ (a direct membrane-depolarizer, 56 mM), DMPP (a selective neuronal nicotinic NN receptor agonist, 100 micrometer) and McN-A-343 (a selective muscarinic M1 receptor agonist, 100 micrometer). Provinol itself did not affect basal CA secretion. Also, in the presence of provinol (1 microgram/ml), the secretory responses of CA evoked by Bay-K-8644 (a voltage-dependent L-type dihydropyridine Ca2+ channel activator, 10 microgram), cyclopiazonic acid (a cytoplasmic Ca2+-ATPase inhibitor, 10 microgram) and veratridine (an activator of voltage-dependent Na+ channels, 10 microgram) were significantly reduced. Interestingly, in the simultaneous presence of provinol (1 microgram/ml) plus L-NAME (a selective inhibitor of NO synthase, 30 micrometer), the CA secretory responses evoked by ACh, high K+, DMPP, McN-A-343, Bay-K-8644 and cyclpiazonic acid recovered to the considerable extent of the corresponding control secretion in comparison with the inhibition of provinol-treatment alone. Under the same condition, the level of NO released from adrenal medulla after the treatment of provinol (3 microgram/ml) was greatly elevated in comparison to its basal release. Taken together, these data demonstrate that provinol inhibits the CA secretory responses evoked by stimulation of cholinergic (both muscarinic and nicotinic) receptors as well as by direct membrane-depolarization from the perfused rat adrenal medulla. This inhibitory effect of provinol seems to be exerted by inhibiting the influx of both calcium and sodium into the rat adrenal medullary cells along with the blockade of Ca2+ release from the cytoplasmic calcium store at least partly through the increased NO production due to the activation of nitric oxide synthase.
(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride ; 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester ; Adrenal Medulla ; Animals ; Calcium ; Catecholamines ; Cytoplasm ; Dihydropyridines ; Dimethylphenylpiperazinium Iodide ; Indoles ; Neurons ; NG-Nitroarginine Methyl Ester ; Nitric Oxide ; Nitric Oxide Synthase ; Rats ; Receptor, Muscarinic M1 ; Receptors, Cholinergic ; Sodium ; Veins ; Veratridine ; Wine

The aim of the present study was to examine the effects of ketamine, a dissociative anesthetics, on secretion of catecholamines (CA) secretion evoked by cholinergic stimulation from the perfused model of the isolated rat adrenal gland, and to establish its mechanism of action, and to compare ketamine effect with that of thiopental sodium, which is one of intravenous barbiturate anesthetics. Ketamine (30~300 micrometer), perfused into an adrenal vein for 60 min, dose- and time-dependently inhibited the CA secretory responses evoked by ACh (5.32 mM), high K+ (a direct membrane- depolarizer, 56 mM), DMPP (a selective neuronal nicotinic NN receptor agonist, 100 micrometer) and McN-A-343 (a selective muscarinic M1 receptor agonist, 100 micrometer). Also, in the presence of ketamine (100 micrometer), the CA secretory responses evoked by veratridine (a voltage-dependent Na+ channel activator, 100 micrometer), Bay-K-8644 (an L-type dihydropyridine Ca2+ channel activator, 10 micrometer), and cyclopiazonic acid (a cytoplasmic Ca2+-ATPase inhibitor, 10 micrometer) were significantly reduced, respectively. Interestingly, thiopental sodium (100 micrometer) also caused the inhibitory effects on the CA secretory responses evoked by ACh, high K+, DMPP, McN-A-343, veratridine, Bay-K-8644, and cyclopiazonic acid. Collectively, these experimental results demonstrate that ketamine inhibits the CA secretion evoked by stimulation of cholinergic (both nicotinic and muscarinic) receptors and the membrane depolarization from the isolated perfused rat adrenal gland. It seems likely that the inhibitory effect of ketamine is mediated by blocking the influx of both Ca2+ and Na+ through voltage-dependent Ca2+ and Na+ channels into the rat adrenal medullary chromaffin cells as well as by inhibiting Ca2+ release from the cytoplasmic calcium store, which are relevant to the blockade of cholinergic receptors. It is also thought that, on the basis of concentrations, ketamine causes similar inhibitory effect with thiopental in the CA secretion from the perfused rat adrenal medulla.
(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride ; 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester ; Adrenal Glands ; Adrenal Medulla ; Anesthetics ; Anesthetics, Dissociative ; Animals ; Barbiturates ; Calcium ; Catecholamines ; Chromaffin Cells ; Cytoplasm ; Dihydropyridines ; Dimethylphenylpiperazinium Iodide ; Indoles ; Ketamine ; Membranes ; Neurons ; Rats ; Receptor, Muscarinic M1 ; Receptors, Cholinergic ; Thiopental ; Veins ; Veratridine

Amlodipine, a calcium channel blocker (CCB) belonging to the group of dihydropyridines, is characterized by a slower onset of action (6-8h), a longer duration of action (24-72h), a greater vascular, cardiac effect, and hyperglycemia. Case of intoxication with 300 mg of amlodipine in a 69-year-old female patient and with 450 mg of amlodipine and 120 mg of glimepride in a 64-year-old female patient caused severe hypotension and hyperglycemia. They were initially treated with fluids, dopamine and norepinephrine, but these therapy were ineffective. Then, the patients were given a bolus injection of insulin and continuous infusion of insulin. The former patient's hyperglycemia was not controlled. She expired in 47 hours. The latter one's hyperglycemia was controlled and then her hypotension improved. In conclusion, it is suggested that hyperinsulinemia-euglycemia therapy be considered as a first-line therapy in calcium channel blocker intoxication.
Aged ; Amlodipine* ; Calcium Channels ; Dihydropyridines ; Dopamine ; Female ; Humans ; Hyperglycemia* ; Hypotension ; Insulin ; Middle Aged ; Norepinephrine

OBJECTIVETo compare the effects of amlodipine, benidipine and nifedipine on myocardial hypertrophy and evaluate the underlying mechanism.

METHODSMyocardial hypertrophy model was created by transverse aortic constriction (TAC) in C57 BL/6 mice, and plasma catecholamine concentrations were measured 7 days after surgery to confirm the sympathetic activation. The 3 drugs were administered in TAC mice for 7 days and cardiac hypertrophy was evaluated according to the heart-to-body weight ratio (HW/BW). Effects of those drugs on the protein synthesis stimulated by phenylephrine in cultured neonatal cardiac myocytes were also examined.

RESULTSHW/BW and plasma concentrations of catecholamine were significantly increased in TAC mice one week after surgery in comparison with to sham-operated mice. One week after TAC, the HW/BW ratio was significantly lower in the amolodipine but not nifedipine-treated group than in the TAC group. Administration of nifedipine via minipump infusion for one week did not decrease HW/BW ratio. Treatment with amlodpine or benidipine, but not nifedipine, decreased the neonatal rat myocyte protein synthesis induced by phenylephrine stimulation.

CONCLUSIONAntihypertrophic effect of DHEs on myocardium is dependent on their potential of blocking N-type calcium channel, and the underlying mechanism involves the sympathetic inhibition.

Amlodipine ; pharmacology ; therapeutic use ; Animals ; Calcium Channel Blockers ; pharmacology ; therapeutic use ; Calcium Channels, N-Type ; drug effects ; Cardiomegaly ; drug therapy ; etiology ; Dihydropyridines ; pharmacology ; therapeutic use ; Disease Models, Animal ; Male ; Mice ; Mice, Inbred C57BL ; Nifedipine ; pharmacology ; therapeutic use

No abstract available.
Beauty ; Dihydropyridines ; Nitrophenols ; Organophosphorus Compounds

OBJECTIVE: Tyrosine kinase inhibitors may be useful in the management of cerebral vasospasm. It has not yet been reported whether L-type Ca2+ channels play a role in tyrosine kinase inhibitors-induced vascular relaxation of cerebral artery. This study was undertaken to clarify the role of L-type Ca2+ channels in tyrosine kinase inhibitors-induced vascular relaxation, and to investigate the effect of tyrosine kinase inhibitors on L-type Ca2+ channels currents in freshly isolated smooth muscle cells from rat basilar artery. METHODS: The isolation of rat basilar smooth muscle cells was performed by special techniques. The whole cell currents were recorded by whole cell patch clamp technique in freshly isolated smooth muscle cells from rat basilar artery. RESULTS: Patch clamp studies revealed a whole-cell current which resembles the L-type Ca2+ current reported by others. The amplitude of this current was decreased by nimodipine and increased by Bay K 8644. Genistein(n=5), tyrphostin A-23(n=3), A-25(n=6) 30micrometer reduced the amplitude of the L-type Ca2+ channel current in whole cell mode. In contrast, diadzein 30 micrometer (n=3), inactive analogue of genistein, did not decrease the amplitude of the L-type Ca2+ channels current. CONCLUSION: These results suggest that tyrosine kinase inhibitors such as genistein, tyrphostin A-23, A-25 may relax cerebral vessel through decreasing level of intracellular calcium, [Ca2+]i, by inhibition of L-type Ca2+ channel.
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester ; Animals ; Basilar Artery ; Calcium* ; Cerebral Arteries ; Genistein ; Muscle, Smooth* ; Myocytes, Smooth Muscle* ; Nimodipine ; Patch-Clamp Techniques ; Protein-Tyrosine Kinases* ; Rats* ; Relaxation ; Tyrosine* ; Vasospasm, Intracranial

Endothelin (ET) is a potent vasoconstrictive 21-amino acid peptide hormone released from vascular endothelium The effects of ET-1 on coronary and systemic hemodynamics in comparison with Bay K 8644, a Ca2+ agonist, were studied in halothane-anesthetized dogs. The modification of ET-1 effects by nicardipine, a voltage-dependent Ca2+ antagonist, was also investigated. Single bolus ET-1 (100 ng/ kg) and Bay K 8644 (30 ug) were administered consecutively into left circumflex coronary artery during intracoronary infusion of either 0.9% saline (0.5 ml/kg/h, n=11) or nicardipine (1 ug/kg/min, n=10). Coronary and systemic hemodynamic parameters were measured just prior to (baseline), during saline or nicardipine infusion and 1, 5, 10, 20, 30, 45, and 60 min after ET-1 injection. Also electrocardiographic changes were observed continuously. The results are as follows: 1) Both ET-1 and Ray K 8644 produced a marked and immediate reduction in coronary blood flow and an increase in coronary vascular resistance. 2) ET-1 evoked coronary vasoconstrictions were long-lasting as compared with transient actions of Bay K 8644. 3) ET-1 reduced peak systolic intramyocardial pressure (IMP), mean aortic pressure (MAP), and cardiac index (CI), in contrast Bay K 8644 increased IMP without any changes in MAP and CL 4) Nicardipine (1 ug/kg/min, i.c) produced a significant increase (2-fold) in coronary blood flow and a reduction (46%) in coronary vascular resistance, whereas other hemodynamic parameters remained unchanged. 5) Nicardipine partially attenuated coronary vascular and systemic effects of ET-1, but it completely prevented those of Bay K 8644. 6) ET-1 (100 ng/kg, i.c.) produced a significant ST segment elevation in electrocardiogram in all cases of the saline group, but in none of the nicardipine group. These findings suggest that ET-1 is a potent and long-lasting coronary vasoconstrictor and that its vasoconstrictive effect is mediated in part by promoting Ca2+ influx through a voltage-dependant Ca2+ channel since nicardipine only partially attenuated ET-1 induced cardiovascular effects.
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester ; Animals ; Arterial Pressure ; Coronary Vessels ; Dogs* ; Electrocardiography ; Endothelin-1* ; Endothelins ; Endothelium, Vascular ; Hemodynamics* ; Nicardipine* ; Vascular Resistance ; Vasoconstriction