Effects of various calcium antagonists in isolated perfused hearts from diabetic and age-matched control rats

J. B. Heijnis; M. J. Mathy; P. A. van Zwieten

doi:10.1097/00005344-199106000-00019

Effects of various calcium antagonists in isolated perfused hearts from diabetic and age-matched control rats

J. B. Heijnis^*
, M. J. Mathy
, P. A. van Zwieten

^*Corresponding author for this work

University of Amsterdam

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

The purpose of this study was to examine the effects of several calcium antagonistic drugs on lest ventricular contraction (isovolumetric) and coronary flow in isolated perfused hearts from streptozotocin diabetic rats compared to age-matched controls, thereby hoping to throw further light on the changes in Ca2+ handling that occur in the diabetic heart. In the presence of Ca2+ (0.99.9 mM) left ventricular pressure (LVP) was not significantly different in either type of heart. From cumulative dose-response curves, pD2 values of various calcium antagonists for the negative inotropic activity were determined in diabetic and control hearts. The pD2 values for several calcium antagonists were significantly greater in diabetic hearts than in controls: 5.72 vs. 4.99 for diltiazem, 6.88 vs. 6.60 for verapamil, and 8.42 vs. 8.04 for (-)-devapamil. In hearts from diabetic rats. LVP was also more sensitive to TMB-8 compared with controls: a higher pEC20 value (instead of the pD2 value) was found (5.47 vs. 5.16). The pD2 values for (+)-devapamil, nifedipine, and ryanodine-were not significantly different in either type of heart. Calcium-entry blockers increased the coronary flow in control hearts (range 60-80% of the initial flow). However, the increase in flow was significantly greater in diabetic hearts than in the controls (95-128%). TMB-8 and ryanodine had no effect on coronary flow in both types of hearts. In conclusion. the changes in sensitivity of LVP to several calcium antagonists may support a different Ca2+ handling in diabetic hearts compared with controls. The greater increase in coronay flow in hearts from diabetic rats in the presence of all calcium-entry blockers studied suggests a greater maximal flow capacity of the coronary bed at a perfusion pressure of 60 mm Hg in the diabetic preparations, which might be an indication of an altered vascular architecutre in the diabetic heart. © 1991 Raven Press, Ltd., New York.

Original language	English
Pages (from-to)	983-989
Journal	Journal of cardiovascular pharmacology
Volume	17
Issue number	6
DOIs	https://doi.org/10.1097/00005344-199106000-00019
Publication status	Published - 1991
Externally published	Yes

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10.1097/00005344-199106000-00019

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title = "Effects of various calcium antagonists in isolated perfused hearts from diabetic and age-matched control rats",

abstract = "The purpose of this study was to examine the effects of several calcium antagonistic drugs on lest ventricular contraction (isovolumetric) and coronary flow in isolated perfused hearts from streptozotocin diabetic rats compared to age-matched controls, thereby hoping to throw further light on the changes in Ca2+ handling that occur in the diabetic heart. In the presence of Ca2+ (0.99.9 mM) left ventricular pressure (LVP) was not significantly different in either type of heart. From cumulative dose-response curves, pD2 values of various calcium antagonists for the negative inotropic activity were determined in diabetic and control hearts. The pD2 values for several calcium antagonists were significantly greater in diabetic hearts than in controls: 5.72 vs. 4.99 for diltiazem, 6.88 vs. 6.60 for verapamil, and 8.42 vs. 8.04 for (-)-devapamil. In hearts from diabetic rats. LVP was also more sensitive to TMB-8 compared with controls: a higher pEC20 value (instead of the pD2 value) was found (5.47 vs. 5.16). The pD2 values for (+)-devapamil, nifedipine, and ryanodine-were not significantly different in either type of heart. Calcium-entry blockers increased the coronary flow in control hearts (range 60-80\% of the initial flow). However, the increase in flow was significantly greater in diabetic hearts than in the controls (95-128\%). TMB-8 and ryanodine had no effect on coronary flow in both types of hearts. In conclusion. the changes in sensitivity of LVP to several calcium antagonists may support a different Ca2+ handling in diabetic hearts compared with controls. The greater increase in coronay flow in hearts from diabetic rats in the presence of all calcium-entry blockers studied suggests a greater maximal flow capacity of the coronary bed at a perfusion pressure of 60 mm Hg in the diabetic preparations, which might be an indication of an altered vascular architecutre in the diabetic heart. {\textcopyright} 1991 Raven Press, Ltd., New York.",

author = "Heijnis, \{J. B.\} and Mathy, \{M. J.\} and \{van Zwieten\}, \{P. A.\}",

year = "1991",

doi = "10.1097/00005344-199106000-00019",

language = "English",

volume = "17",

pages = "983--989",

journal = "Journal of cardiovascular pharmacology",

issn = "0160-2446",

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T1 - Effects of various calcium antagonists in isolated perfused hearts from diabetic and age-matched control rats

AU - Heijnis, J. B.

AU - Mathy, M. J.

AU - van Zwieten, P. A.

PY - 1991

Y1 - 1991

N2 - The purpose of this study was to examine the effects of several calcium antagonistic drugs on lest ventricular contraction (isovolumetric) and coronary flow in isolated perfused hearts from streptozotocin diabetic rats compared to age-matched controls, thereby hoping to throw further light on the changes in Ca2+ handling that occur in the diabetic heart. In the presence of Ca2+ (0.99.9 mM) left ventricular pressure (LVP) was not significantly different in either type of heart. From cumulative dose-response curves, pD2 values of various calcium antagonists for the negative inotropic activity were determined in diabetic and control hearts. The pD2 values for several calcium antagonists were significantly greater in diabetic hearts than in controls: 5.72 vs. 4.99 for diltiazem, 6.88 vs. 6.60 for verapamil, and 8.42 vs. 8.04 for (-)-devapamil. In hearts from diabetic rats. LVP was also more sensitive to TMB-8 compared with controls: a higher pEC20 value (instead of the pD2 value) was found (5.47 vs. 5.16). The pD2 values for (+)-devapamil, nifedipine, and ryanodine-were not significantly different in either type of heart. Calcium-entry blockers increased the coronary flow in control hearts (range 60-80% of the initial flow). However, the increase in flow was significantly greater in diabetic hearts than in the controls (95-128%). TMB-8 and ryanodine had no effect on coronary flow in both types of hearts. In conclusion. the changes in sensitivity of LVP to several calcium antagonists may support a different Ca2+ handling in diabetic hearts compared with controls. The greater increase in coronay flow in hearts from diabetic rats in the presence of all calcium-entry blockers studied suggests a greater maximal flow capacity of the coronary bed at a perfusion pressure of 60 mm Hg in the diabetic preparations, which might be an indication of an altered vascular architecutre in the diabetic heart. © 1991 Raven Press, Ltd., New York.

AB - The purpose of this study was to examine the effects of several calcium antagonistic drugs on lest ventricular contraction (isovolumetric) and coronary flow in isolated perfused hearts from streptozotocin diabetic rats compared to age-matched controls, thereby hoping to throw further light on the changes in Ca2+ handling that occur in the diabetic heart. In the presence of Ca2+ (0.99.9 mM) left ventricular pressure (LVP) was not significantly different in either type of heart. From cumulative dose-response curves, pD2 values of various calcium antagonists for the negative inotropic activity were determined in diabetic and control hearts. The pD2 values for several calcium antagonists were significantly greater in diabetic hearts than in controls: 5.72 vs. 4.99 for diltiazem, 6.88 vs. 6.60 for verapamil, and 8.42 vs. 8.04 for (-)-devapamil. In hearts from diabetic rats. LVP was also more sensitive to TMB-8 compared with controls: a higher pEC20 value (instead of the pD2 value) was found (5.47 vs. 5.16). The pD2 values for (+)-devapamil, nifedipine, and ryanodine-were not significantly different in either type of heart. Calcium-entry blockers increased the coronary flow in control hearts (range 60-80% of the initial flow). However, the increase in flow was significantly greater in diabetic hearts than in the controls (95-128%). TMB-8 and ryanodine had no effect on coronary flow in both types of hearts. In conclusion. the changes in sensitivity of LVP to several calcium antagonists may support a different Ca2+ handling in diabetic hearts compared with controls. The greater increase in coronay flow in hearts from diabetic rats in the presence of all calcium-entry blockers studied suggests a greater maximal flow capacity of the coronary bed at a perfusion pressure of 60 mm Hg in the diabetic preparations, which might be an indication of an altered vascular architecutre in the diabetic heart. © 1991 Raven Press, Ltd., New York.

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UR - https://www.ncbi.nlm.nih.gov/pubmed/1714025

U2 - 10.1097/00005344-199106000-00019

DO - 10.1097/00005344-199106000-00019

M3 - Article

C2 - 1714025

SN - 0160-2446

VL - 17

SP - 983

EP - 989

JO - Journal of cardiovascular pharmacology

JF - Journal of cardiovascular pharmacology

IS - 6

ER -

Effects of various calcium antagonists in isolated perfused hearts from diabetic and age-matched control rats

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