ABSTRACT
The effect of methoxyverapamil and diltiazem [calcium antagonists] and morphine [calcium antagonist activity] on the formation of irreversibly sickled cells [ISCs] was investigated. Methoxyverapamil at therapeutic concentration and 10 times that level resulted in a 12% and 21% reduction in the formation of ISCs respectively, which was statistically significant. Diltiazem also produced a significant reduction in ISCs but morphine produced no significant reduction. Combination of these drugs produced a net effect similar to their individual effects. These drugs might be useful in decreasing the intensity of sickling crises and vaso-occlusive events. Thus in vivo trials in patients with sickle-cell disease are suggested
Subject(s)
Humans , Anemia, Sickle Cell/therapy , Gallopamil , Diltiazem , Morphine , Calcium/analysis , Calcium/antagonists & inhibitorsABSTRACT
The Na+ -K+ -activated ATPase is required to maintain osmotic balance and stabilize cell volume. The Na+ -K+ -ATPase has a more direct role in regulating cell volume; it controls the solute concentrations inside the cell, thereby regulating the osmotic forces that can make a cell swell or shrink. The impotance of the Na+ -K+ -ATPase in controlling cell volume is indicated by the observation that animal cells swell, and may burst, if they are treated with ouabain, which, inhibits the Na+ -K+ -ATPase. The present experiment was designed and carried out to determine the effect of verapamil, a calcium blocker, on the activity of Na+ -K+ -ATPase prepared from renal medulla in the normal rabbit. It was reported that verapamil, a well known coronary vasodilator, possessed negative inotropic effects. The mechanism of action of verapamil was initially thought to be due to coronary vasodilation and blockade of myocardial B-adrenergic receptors. 1t was termed such agent calcium antagonist. A derivative of verapamil, D-600, was subsequently shown to block the movement of calcium through the slow channel and thereby after the plateau phase of the cardiac action potential. Verapamil do not directly antagonize the effects of calcium. Rather, it inhibit the entry of ealcium into cells or its mobilization form intracellular stores and, as such, have been termed a calcium channel blocker.
Subject(s)
Animals , Action Potentials , Adenosine Triphosphatases , Adenosine , Calcium , Calcium Channels , Cell Size , Gallopamil , Ouabain , Vasodilation , VerapamilSubject(s)
Animals , Gallopamil/pharmacology , Ion Channels/drug effects , Lanthanum/pharmacology , Synaptic Transmission/drug effects , Calcium Channels/drug effects , Membrane Potentials/drug effects , Muscle Contraction/drug effects , Neuromuscular Junction/drug effects , Rana pipiens , Sarcoplasmic Reticulum/drug effectsABSTRACT
A finalidade deste estudo foi avaliar os efeitos de metoxi-verapamil (D-600) na mortalidade e no tamanho final do infarto, em ratos com oclusao coronariana. Inicialmente, o tronco comum da coronaria esquerda foi ocluido em 212 ratos. Os animais foram randomizados em um grupo controle e um grupo tratado com D-600. A mortalidade apos os primeiros 15 minutos da oclusao do tronco comum da arteria coronaria esquerda era 40% menor no grupo tratado que no grupo controle (p < 0,01). A diferenca de mortalidade entre os dois grupos manteve-se 48 horas apos a oclusao. Os ratos que sobreviveram 48 horas apos-oclusao coronaria tiveram seus infartos medidos por planimetria e os resultados foram: 38,2% no grupo controle e 37,6% no grupo tratado. Estes resultados permitem-nos concluir que D-600 diminui a mortalidade apos oclusao coronariana em ratos, provavelmente por acao antiarritmica