Effects of diltiazem on the physicochemical properties of rat erythrocyte and liposome membrane: Comparison with pentoxifylline and propranolol.

Sasaki, Yoshiyuki; Morita, Takashi; Takeyama, Shigeyuki

doi:10.1254/jjp.34.417

Cited by 16 publications

(4 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We, however, speculate that 1) the inhibition of calcium influx with diltiazem may alter the intracellular ratio of sodium to calcium, which in turn may activate the ouabain-sensitive Na + ,K + -ATPase as a compensatory mechanism, and 2) changes in the membrane conformation caused by diltiazem binding could directly stimulate the ouabainsensitive pump activity. Recently, Sasaki et al 27 showed that diltiazem improved the structural deformability of rat erythrocytes. Rachkov and Pashukov 28 have also shown that reduced ATPase activity of rabbit erythrocytes with vasorenal hypertension is normalized with vasodilatory drugs such as papaverine, pentamin, and nicotinic acid, and this may also be true of diltiazem.…”

Section: Discussionmentioning

confidence: 99%

Effects of diltiazem on cation transport across erythrocyte membranes of hypertensive humans.

Khalil-Manesh¹,

Venkataraman²,

Samant³

et al. 1987

Hypertension

View full text Add to dashboard Cite

SUMMARY The effects of the calcium antagonist diltiazem on diastolic blood pressure and various parameters of erythrocyte membrane cation transport were evaluated in hypertensive patients with diastolic blood pressure between 95 and 110 mm Hg in a placebo-controlled, double-blind parallel study. Twenty-one patients completed the study; 13 received placebo, while 8 received diltiazem. Diastolic blood pressure, intracellular sodium and calcium concentrations, ouabain-sensitive Na + ,K + -adenosine triphosphatase (ATPase) activity, and net sodium efflux and potassium influx across red blood cell membranes were examined in both groups at the end of placebo run-in, at the end of the titration phase, and at the completion of study. In the placebo group, none of the parameters changed significantly. In the drug-treated group, diastolic blood pressure declined by approximately 10% (placebo, 95.1 ± 8.9; drug-treated, 86.9 ± 4.9 mm Hg; p<0.03) at the end of the study. There were also reductions in intracellular sodium (placebo, 7.9 ± 1.8; drug-treated, 5.2 ± 0.4 mmol/L cells; p<0.002) and calcium (placebo, 13.5 ± 1.6; drug-treated 10.8 ± 3.3 Mmol/L cells; p<0.03) concentrations, accompanied by a simultaneous rise in the activity of the ouabain-sensitive Na+ ,K + -ATPase of erythrocyte membranes (placebo, 7.1 ± 1.1 x 10-J ; drug-treated, 9.0 ± 0.6 x 10-2 fiM inorganic pbosphate/hr/mg; p < 0.001) at the end of the study. However, no significant change in the ouabaininsensitive moiety of the ATPase pump was found. Diltiazem treatment increased net sodium efflux and potassium influx. It is concluded that diltiazem reduces diastolic blood pressure of hypertensive subjects. Erythrocyte studies indicate that diltiazem not only blocks entrance of calcium into the cells but may also stimulate Na+,K+-ATPase activity, resulting in reduction in intracellular sodium concentration, thus suggesting a possible dual mechanism for its antihypertensive effects. 18In the present investigation, we studied the changes that occur in the erythrocytes of hypertensive persons treated with diltiazem to test the hypothesis that the abnormalities in the red blood cell cation concentrations and various pump activities are reversed in those who respond to the drug treatment. These studies were conducted in a placebo-controlled, double-blind, parallel fashion. Patients and Methods Selection of Study PatientsThe protocol was approved by the institutional review board, and written informed consent was obtained from each subject. Twenty-one patients, 12 men (average age, 51 ± 15 years) and 9 women (average age, 57 ± 13 years), completed the protocol. Inclusion criteria were 1) a stable resting supine diastolic blood pressure (DBP) between 95 and 110 mm Hg at least 2 weeks after cessation of antihypertensive medications and 2) a stable DBP with variation of 7 mm Hg or less 19between two consecutive weekly measurements starting with days 7 through 10 of the placebo run-in.After a 2-week placebo run-in phase, the eligible patients were randomized to placebo...

show abstract

Section: Discussionmentioning

confidence: 99%

Effects of diltiazem on cation transport across erythrocyte membranes of hypertensive humans.

Khalil-Manesh¹,

Venkataraman²,

Samant³

et al. 1987

Hypertension

View full text Add to dashboard Cite

show abstract

“…(+)-cis-Diltiazem has an inhibitory action on Na+-K+ ATPase in erythrocyte ghosts (Sasaki et al, 1984), this action being the action of (+)-cis-diltiazem unrelated to calcium channel blockade. Because the positive inotropic action of cardiac glycosides has been considered to be due to inhibition of the sarcolemmal Na+-K+ ATPase, we attempted to compare the positive inotropic effect of (-)-cis-diltiazem with that of ouabain.…”

Section: Discussionmentioning

confidence: 98%

“…Nevertheless, there are some effects of (-)-cis-diltiazem which are similar or superior to those of (+)-cis-diltiazem in potency. For example, (-)-cis-diltiazem inhibits platelet aggregation and microviscosity of both erythrocyte ghosts and liposomes to a similar degree to (+ )-cis-diltiazem (Kiyomoto et al, 1983;Sasaki et al, 1984). This suggests that either (+)-cisor (-)-cis-diltiazem has an action, which may not be related to its calcium channel blocking action.…”

Section: Introductionmentioning

confidence: 99%

Positive inotropic and negative chronotropic effects of (−)‐cis‐diltiazem in rat isolated atria

Nasa

Ichihara

Yoshida

et al. 1992

British J Pharmacology

View full text Add to dashboard Cite

1 The cardiovascular effects of (-)-cis-diltiazem, an optical isomer of diltiazem, were studied in the isolated atrium and aortic strip. (-)-cis-Diltiazem (30,pM or more) increased the developed tension of the rat left atrium, while (+ )-cis-diltiazem (1 ,UM or more) decreased it.2 (-)-cis-Diltiazem (1 to 100pM) decreased the rate of spontaneous beating in the right atrium as did (+ -cis-diltiazem. 3 The potency of the positive inotropic action of (-)-cis-diltiazem was almost the same as that of ouabain in the rat left atrium, but in the guinea-pig left atrium it was considerably weaker than that of ouabain.4 In both endothelium-intact and endothelium-denuded aortic strips, (-)-cis-diltiazem relaxed the Ca2 -induced contraction. In the endothelium-intact rat aortic strip depolarized by 15mM KC1, Bay K 8644, a calcium channel agonist, increased the contractile force, whereas (-)cis-diltiazem did not. 5 These results indicate that (-)-cis-diltiazem has a positive inotropic action in isolated atria in rats and guinea-pigs, but the mode of positive inotropic action of (-)-cis-diltiazem is different from that of ouabain or Bay K 8644.

show abstract

“…The membranestabilizing action of drugs has been evaluated extensively in the erythrocyte. For example, propranolol, nicardipine, diltiazem and lidocaine protect the erythrocyte membrane against hypotonic haemolysis (Sasaki et al 1984; Rogers et a1 1986;Abe et a1 1991). Furthermore, anti-ischaemic drugs are shown to reduce haemolysis induced by amphiphilic metabolites.…”

mentioning

confidence: 99%

Protective Effects of Dilazep and its Derivative K-7259 on the Haemolysis Induced by Amphiphiles in Rat Erythrocytes

Hara

Hayase

Hashizume

et al. 1997

Journal of Pharmacy and Pharmacology

View full text Add to dashboard Cite

The effects of dilazep and K-7259, a dilazep derivative, on the haemolysis (as evidenced by release of haemoglobin) induced by palmitoyl-L-carnitine (PAL-CAR) or palmitoyl 1-alpha-lysophosphatidylcholine (PAL-LPC) have been determined in rat erythrocytes. At concentrations above the critical micelle concentration both PAL-CAR and PAL-LPC induced haemolysis; the concentrations of PAL-CAR and PAL-LPC producing 50% haemolysis were approximately 13 and 14 microM, respectively. The 50% haemolysis induced by PAL-CAR or PAL-LPC was attenuated by dilazep (1, 10 or 100 microM) but not at the highest concentration used (1 mM). K-7259 attenuated the 50% haemolysis induced by PAL-CAR or PAL-LPC at concentrations ranging from 1 microM to 1 mM. Similarly, dilazep (1 to 100 microM) and K-7259 (1 microM to 1 mM) significantly or insignificantly attenuated the 25% and 75% haemolysis induced by PAL-CAR or PAL-LPC. Neither dilazep nor K-7259 affected micelle formation by PAL-CAR or PAL-LPC, nor, at concentrations of 1 and 10 microM, did they attenuate the haemolysis induced by osmotic imbalance (hypotonic haemolysis). These results suggest that both dilazep and K-7259 protect the erythrocyte membrane from the damage induced by PAL-CAR or PAL-LPC. The protective effects of dilazep and K-7259 are mediated by some mechanism other than prevention of micelle formation or protection of the erythrocyte membrane against osmotic imbalance.

show abstract

Effects of diltiazem on the physicochemical properties of rat erythrocyte and liposome membrane: Comparison with pentoxifylline and propranolol.

Abstract: Abstract-In vitro effects of the coronary vasodilator diltiazem on rat erythrocytes and liposomes were studied in comparison with propranolol and pentoxifylline.

Cited by 16 publications

References 28 publications

Effects of diltiazem on cation transport across erythrocyte membranes of hypertensive humans.

Effects of diltiazem on cation transport across erythrocyte membranes of hypertensive humans.

Positive inotropic and negative chronotropic effects of (−)‐cis‐diltiazem in rat isolated atria

Protective Effects of Dilazep and its Derivative K-7259 on the Haemolysis Induced by Amphiphiles in Rat Erythrocytes

Contact Info

Product

Resources

About