The effect of a new calcium channel blocker (TA-3090) on lipoprotein profile and intestinal lipid handling in rodents

E. Levy, Lesley J Smith, L. Dumont, D. Garceau, C. Garofalo, L. Thibault, E. Seidman

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Recent interest has focused on findings that drugs used to lower blood pressure may adversely modify plasma lipids and lipoprotein metabolism. This observation may explain why pharmacologic control of hypertension has failed to reduce the incidence of morbidity and mortality from coronary artery disease. The present study aims to evaluate the effect of TA-3090, a new calcium channel blocker, on fasting plasma lipids and lipoproteins, as well as on processes of intestinal fat absorption. Rats were treated by gavage with TA-3090 (10 mg/kg twice daily) for 4 days and compared with controls (n = 6 per group). Plasma cholesterol was increased in the treated group to (mean ± SE) 74 ± 2 vs 60 ± 4 mg/dl (P <0.01), due mainly to an increased high density lipoprotein-cholesterol level (50 ± 2 vs 37 ± 3 mg/dl, P <0.005). Notably plasma triglycerides (TG) and low density lipoprotein- cholesterol were not significantly affected. Another group of TA-3090-treated animals was given an intraduodenal fat meal, and the rise in plasma TG and chylomicrons followed over 4 hr. Postprandial hypertriglyceridemia and chylomicronemia were significantly lower at 2 hr (P <0.05) and 3 hr (P <0.01) compared with controls. In a separate group of animals, the addition of TA-3090 to a 2% Intralipid infusion intraduodenally was associated with significantly reduced TG and chylomicron-TG transport into lymph (P <0.05). Furthermore, experiments in rats pretreated with TA-3090 intraperitoneally and then given 2% Intralipid intraduodenally were shown to have a significant decrease in mean flow rate (27%), TG transport (31%) and chylomicron-TG output (37%), when compared with controls. In vitro studies using jejunal organ culture to examine the effect of TA-3090 on intracellular lipid synthesis and secretion revealed that the addition of the drug to the medium resulted in significantly decreased TG synthesis and secretion. These data suggest that TA-3090 could be effective in increasing HDL-cholesterol and reducing postprandial chylomicronemia. Our findings support a role for TA- 3090 directly on enterocyte absorption and/or intracellular lipid transport, and thus indicate the importance of intracellular calcium on these processes.

Original languageEnglish (US)
Pages (from-to)128-135
Number of pages8
JournalProceedings of the Society for Experimental Biology and Medicine
Volume199
Issue number1
StatePublished - 1992
Externally publishedYes

Fingerprint

Calcium Channel Blockers
Lipoproteins
Rodentia
Triglycerides
Lipids
Chylomicrons
Plasmas
HDL Cholesterol
Rats
Animals
Fats
clentiazem
Handling (Psychology)
Enterocytes
Hypertriglyceridemia
Organ Culture Techniques
Intestinal Absorption
Blood pressure
Lymph
Lipid Metabolism

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

The effect of a new calcium channel blocker (TA-3090) on lipoprotein profile and intestinal lipid handling in rodents. / Levy, E.; Smith, Lesley J; Dumont, L.; Garceau, D.; Garofalo, C.; Thibault, L.; Seidman, E.

In: Proceedings of the Society for Experimental Biology and Medicine, Vol. 199, No. 1, 1992, p. 128-135.

Research output: Contribution to journalArticle

Levy, E, Smith, LJ, Dumont, L, Garceau, D, Garofalo, C, Thibault, L & Seidman, E 1992, 'The effect of a new calcium channel blocker (TA-3090) on lipoprotein profile and intestinal lipid handling in rodents', Proceedings of the Society for Experimental Biology and Medicine, vol. 199, no. 1, pp. 128-135.
Levy, E. ; Smith, Lesley J ; Dumont, L. ; Garceau, D. ; Garofalo, C. ; Thibault, L. ; Seidman, E. / The effect of a new calcium channel blocker (TA-3090) on lipoprotein profile and intestinal lipid handling in rodents. In: Proceedings of the Society for Experimental Biology and Medicine. 1992 ; Vol. 199, No. 1. pp. 128-135.
@article{75aebf415501452bbcb15d448686d24a,
title = "The effect of a new calcium channel blocker (TA-3090) on lipoprotein profile and intestinal lipid handling in rodents",
abstract = "Recent interest has focused on findings that drugs used to lower blood pressure may adversely modify plasma lipids and lipoprotein metabolism. This observation may explain why pharmacologic control of hypertension has failed to reduce the incidence of morbidity and mortality from coronary artery disease. The present study aims to evaluate the effect of TA-3090, a new calcium channel blocker, on fasting plasma lipids and lipoproteins, as well as on processes of intestinal fat absorption. Rats were treated by gavage with TA-3090 (10 mg/kg twice daily) for 4 days and compared with controls (n = 6 per group). Plasma cholesterol was increased in the treated group to (mean ± SE) 74 ± 2 vs 60 ± 4 mg/dl (P <0.01), due mainly to an increased high density lipoprotein-cholesterol level (50 ± 2 vs 37 ± 3 mg/dl, P <0.005). Notably plasma triglycerides (TG) and low density lipoprotein- cholesterol were not significantly affected. Another group of TA-3090-treated animals was given an intraduodenal fat meal, and the rise in plasma TG and chylomicrons followed over 4 hr. Postprandial hypertriglyceridemia and chylomicronemia were significantly lower at 2 hr (P <0.05) and 3 hr (P <0.01) compared with controls. In a separate group of animals, the addition of TA-3090 to a 2{\%} Intralipid infusion intraduodenally was associated with significantly reduced TG and chylomicron-TG transport into lymph (P <0.05). Furthermore, experiments in rats pretreated with TA-3090 intraperitoneally and then given 2{\%} Intralipid intraduodenally were shown to have a significant decrease in mean flow rate (27{\%}), TG transport (31{\%}) and chylomicron-TG output (37{\%}), when compared with controls. In vitro studies using jejunal organ culture to examine the effect of TA-3090 on intracellular lipid synthesis and secretion revealed that the addition of the drug to the medium resulted in significantly decreased TG synthesis and secretion. These data suggest that TA-3090 could be effective in increasing HDL-cholesterol and reducing postprandial chylomicronemia. Our findings support a role for TA- 3090 directly on enterocyte absorption and/or intracellular lipid transport, and thus indicate the importance of intracellular calcium on these processes.",
author = "E. Levy and Smith, {Lesley J} and L. Dumont and D. Garceau and C. Garofalo and L. Thibault and E. Seidman",
year = "1992",
language = "English (US)",
volume = "199",
pages = "128--135",
journal = "Experimental Biology and Medicine",
issn = "0037-9727",
publisher = "Society for Experimental Biology and Medicine",
number = "1",

}

TY - JOUR

T1 - The effect of a new calcium channel blocker (TA-3090) on lipoprotein profile and intestinal lipid handling in rodents

AU - Levy, E.

AU - Smith, Lesley J

AU - Dumont, L.

AU - Garceau, D.

AU - Garofalo, C.

AU - Thibault, L.

AU - Seidman, E.

PY - 1992

Y1 - 1992

N2 - Recent interest has focused on findings that drugs used to lower blood pressure may adversely modify plasma lipids and lipoprotein metabolism. This observation may explain why pharmacologic control of hypertension has failed to reduce the incidence of morbidity and mortality from coronary artery disease. The present study aims to evaluate the effect of TA-3090, a new calcium channel blocker, on fasting plasma lipids and lipoproteins, as well as on processes of intestinal fat absorption. Rats were treated by gavage with TA-3090 (10 mg/kg twice daily) for 4 days and compared with controls (n = 6 per group). Plasma cholesterol was increased in the treated group to (mean ± SE) 74 ± 2 vs 60 ± 4 mg/dl (P <0.01), due mainly to an increased high density lipoprotein-cholesterol level (50 ± 2 vs 37 ± 3 mg/dl, P <0.005). Notably plasma triglycerides (TG) and low density lipoprotein- cholesterol were not significantly affected. Another group of TA-3090-treated animals was given an intraduodenal fat meal, and the rise in plasma TG and chylomicrons followed over 4 hr. Postprandial hypertriglyceridemia and chylomicronemia were significantly lower at 2 hr (P <0.05) and 3 hr (P <0.01) compared with controls. In a separate group of animals, the addition of TA-3090 to a 2% Intralipid infusion intraduodenally was associated with significantly reduced TG and chylomicron-TG transport into lymph (P <0.05). Furthermore, experiments in rats pretreated with TA-3090 intraperitoneally and then given 2% Intralipid intraduodenally were shown to have a significant decrease in mean flow rate (27%), TG transport (31%) and chylomicron-TG output (37%), when compared with controls. In vitro studies using jejunal organ culture to examine the effect of TA-3090 on intracellular lipid synthesis and secretion revealed that the addition of the drug to the medium resulted in significantly decreased TG synthesis and secretion. These data suggest that TA-3090 could be effective in increasing HDL-cholesterol and reducing postprandial chylomicronemia. Our findings support a role for TA- 3090 directly on enterocyte absorption and/or intracellular lipid transport, and thus indicate the importance of intracellular calcium on these processes.

AB - Recent interest has focused on findings that drugs used to lower blood pressure may adversely modify plasma lipids and lipoprotein metabolism. This observation may explain why pharmacologic control of hypertension has failed to reduce the incidence of morbidity and mortality from coronary artery disease. The present study aims to evaluate the effect of TA-3090, a new calcium channel blocker, on fasting plasma lipids and lipoproteins, as well as on processes of intestinal fat absorption. Rats were treated by gavage with TA-3090 (10 mg/kg twice daily) for 4 days and compared with controls (n = 6 per group). Plasma cholesterol was increased in the treated group to (mean ± SE) 74 ± 2 vs 60 ± 4 mg/dl (P <0.01), due mainly to an increased high density lipoprotein-cholesterol level (50 ± 2 vs 37 ± 3 mg/dl, P <0.005). Notably plasma triglycerides (TG) and low density lipoprotein- cholesterol were not significantly affected. Another group of TA-3090-treated animals was given an intraduodenal fat meal, and the rise in plasma TG and chylomicrons followed over 4 hr. Postprandial hypertriglyceridemia and chylomicronemia were significantly lower at 2 hr (P <0.05) and 3 hr (P <0.01) compared with controls. In a separate group of animals, the addition of TA-3090 to a 2% Intralipid infusion intraduodenally was associated with significantly reduced TG and chylomicron-TG transport into lymph (P <0.05). Furthermore, experiments in rats pretreated with TA-3090 intraperitoneally and then given 2% Intralipid intraduodenally were shown to have a significant decrease in mean flow rate (27%), TG transport (31%) and chylomicron-TG output (37%), when compared with controls. In vitro studies using jejunal organ culture to examine the effect of TA-3090 on intracellular lipid synthesis and secretion revealed that the addition of the drug to the medium resulted in significantly decreased TG synthesis and secretion. These data suggest that TA-3090 could be effective in increasing HDL-cholesterol and reducing postprandial chylomicronemia. Our findings support a role for TA- 3090 directly on enterocyte absorption and/or intracellular lipid transport, and thus indicate the importance of intracellular calcium on these processes.

UR - http://www.scopus.com/inward/record.url?scp=0026514197&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026514197&partnerID=8YFLogxK

M3 - Article

C2 - 1728031

AN - SCOPUS:0026514197

VL - 199

SP - 128

EP - 135

JO - Experimental Biology and Medicine

JF - Experimental Biology and Medicine

SN - 0037-9727

IS - 1

ER -