Cardiovascular effects of conventional sulfonylureas and glimepiride

K. Geisen, A. Végh, E. Krause, J. Papp

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

Sulfonylureas have, in the past, been reported to have adverse cardiovascular effects. Glimepiride is a new sulfonylurea. In spite of stimulating less insulin secretion, it has, depending on the species, equal or higher blood glucose decreasing activity and according to preliminary studies less cardiovascular activity than glibenclamide. Further studies were performed to confirm the lower cardiovascular activity of glimepiride. The IC50 for inhibition of rilmakalim-activate K(ATP) channel currents in isolated ventricular myocytes was 31.6 nM for glimepiride and 6.8 nM for glibenclamide. In endotoxin shock-rats at a dose of 1 x 2 mg/kg i.v., glibenclamide induced a significantly higher blood pressure increase than glimepiride. At two i.v. doses of 20 mg/kg 4 min apart, in normal rats, glibenclamide produced signs of ischemia in the ECG in nearly animals, glimepiride almost none, in diabetic rats, glibenclamide produced in all animals a lethal cardiogenic shock preceeded by serious ECG changes, glimepiride only in one fifth of the animals. In open-chest dogs, on intracoronary infusion of equieffective blood glucose-lowering doses, glibenclamide, gliclazide and glimepiride all reduced coronary blood flow, increased coronary resistance, depressed the mechanical activity of the heart, enhanced myocardial O2-extraction, reduced the serum potassium level and induced a moderate endocardial ST-segment elevation, but glimepiride to a significantly less extent than glibenclamide and gliclazide. The presented data confirm that glimepiride at equivalent blood glucose decreasing doses has less cardiovascular activity than conventional sulfonylureas.

Original languageEnglish
Pages (from-to)496-507
Number of pages12
JournalHormone and Metabolic Research
Volume28
Issue number9
Publication statusPublished - 1996

Fingerprint

glimepiride
Glyburide
Gliclazide
Blood Glucose
Rats
Animals
Electrocardiography
Cardiogenic Shock
Blood pressure
Endotoxins

Keywords

  • Cardiovascular activity
  • Glibenclamide
  • Gliclazide
  • Glimepiride
  • K(ATP) channel
  • Sulfonylureas

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology

Cite this

Cardiovascular effects of conventional sulfonylureas and glimepiride. / Geisen, K.; Végh, A.; Krause, E.; Papp, J.

In: Hormone and Metabolic Research, Vol. 28, No. 9, 1996, p. 496-507.

Research output: Contribution to journalArticle

@article{736f584ec7c14e7497178cdafab049e7,
title = "Cardiovascular effects of conventional sulfonylureas and glimepiride",
abstract = "Sulfonylureas have, in the past, been reported to have adverse cardiovascular effects. Glimepiride is a new sulfonylurea. In spite of stimulating less insulin secretion, it has, depending on the species, equal or higher blood glucose decreasing activity and according to preliminary studies less cardiovascular activity than glibenclamide. Further studies were performed to confirm the lower cardiovascular activity of glimepiride. The IC50 for inhibition of rilmakalim-activate K(ATP) channel currents in isolated ventricular myocytes was 31.6 nM for glimepiride and 6.8 nM for glibenclamide. In endotoxin shock-rats at a dose of 1 x 2 mg/kg i.v., glibenclamide induced a significantly higher blood pressure increase than glimepiride. At two i.v. doses of 20 mg/kg 4 min apart, in normal rats, glibenclamide produced signs of ischemia in the ECG in nearly animals, glimepiride almost none, in diabetic rats, glibenclamide produced in all animals a lethal cardiogenic shock preceeded by serious ECG changes, glimepiride only in one fifth of the animals. In open-chest dogs, on intracoronary infusion of equieffective blood glucose-lowering doses, glibenclamide, gliclazide and glimepiride all reduced coronary blood flow, increased coronary resistance, depressed the mechanical activity of the heart, enhanced myocardial O2-extraction, reduced the serum potassium level and induced a moderate endocardial ST-segment elevation, but glimepiride to a significantly less extent than glibenclamide and gliclazide. The presented data confirm that glimepiride at equivalent blood glucose decreasing doses has less cardiovascular activity than conventional sulfonylureas.",
keywords = "Cardiovascular activity, Glibenclamide, Gliclazide, Glimepiride, K(ATP) channel, Sulfonylureas",
author = "K. Geisen and A. V{\'e}gh and E. Krause and J. Papp",
year = "1996",
language = "English",
volume = "28",
pages = "496--507",
journal = "Hormone and Metabolic Research",
issn = "0018-5043",
publisher = "Georg Thieme Verlag",
number = "9",

}

TY - JOUR

T1 - Cardiovascular effects of conventional sulfonylureas and glimepiride

AU - Geisen, K.

AU - Végh, A.

AU - Krause, E.

AU - Papp, J.

PY - 1996

Y1 - 1996

N2 - Sulfonylureas have, in the past, been reported to have adverse cardiovascular effects. Glimepiride is a new sulfonylurea. In spite of stimulating less insulin secretion, it has, depending on the species, equal or higher blood glucose decreasing activity and according to preliminary studies less cardiovascular activity than glibenclamide. Further studies were performed to confirm the lower cardiovascular activity of glimepiride. The IC50 for inhibition of rilmakalim-activate K(ATP) channel currents in isolated ventricular myocytes was 31.6 nM for glimepiride and 6.8 nM for glibenclamide. In endotoxin shock-rats at a dose of 1 x 2 mg/kg i.v., glibenclamide induced a significantly higher blood pressure increase than glimepiride. At two i.v. doses of 20 mg/kg 4 min apart, in normal rats, glibenclamide produced signs of ischemia in the ECG in nearly animals, glimepiride almost none, in diabetic rats, glibenclamide produced in all animals a lethal cardiogenic shock preceeded by serious ECG changes, glimepiride only in one fifth of the animals. In open-chest dogs, on intracoronary infusion of equieffective blood glucose-lowering doses, glibenclamide, gliclazide and glimepiride all reduced coronary blood flow, increased coronary resistance, depressed the mechanical activity of the heart, enhanced myocardial O2-extraction, reduced the serum potassium level and induced a moderate endocardial ST-segment elevation, but glimepiride to a significantly less extent than glibenclamide and gliclazide. The presented data confirm that glimepiride at equivalent blood glucose decreasing doses has less cardiovascular activity than conventional sulfonylureas.

AB - Sulfonylureas have, in the past, been reported to have adverse cardiovascular effects. Glimepiride is a new sulfonylurea. In spite of stimulating less insulin secretion, it has, depending on the species, equal or higher blood glucose decreasing activity and according to preliminary studies less cardiovascular activity than glibenclamide. Further studies were performed to confirm the lower cardiovascular activity of glimepiride. The IC50 for inhibition of rilmakalim-activate K(ATP) channel currents in isolated ventricular myocytes was 31.6 nM for glimepiride and 6.8 nM for glibenclamide. In endotoxin shock-rats at a dose of 1 x 2 mg/kg i.v., glibenclamide induced a significantly higher blood pressure increase than glimepiride. At two i.v. doses of 20 mg/kg 4 min apart, in normal rats, glibenclamide produced signs of ischemia in the ECG in nearly animals, glimepiride almost none, in diabetic rats, glibenclamide produced in all animals a lethal cardiogenic shock preceeded by serious ECG changes, glimepiride only in one fifth of the animals. In open-chest dogs, on intracoronary infusion of equieffective blood glucose-lowering doses, glibenclamide, gliclazide and glimepiride all reduced coronary blood flow, increased coronary resistance, depressed the mechanical activity of the heart, enhanced myocardial O2-extraction, reduced the serum potassium level and induced a moderate endocardial ST-segment elevation, but glimepiride to a significantly less extent than glibenclamide and gliclazide. The presented data confirm that glimepiride at equivalent blood glucose decreasing doses has less cardiovascular activity than conventional sulfonylureas.

KW - Cardiovascular activity

KW - Glibenclamide

KW - Gliclazide

KW - Glimepiride

KW - K(ATP) channel

KW - Sulfonylureas

UR - http://www.scopus.com/inward/record.url?scp=0029808746&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029808746&partnerID=8YFLogxK

M3 - Article

VL - 28

SP - 496

EP - 507

JO - Hormone and Metabolic Research

JF - Hormone and Metabolic Research

SN - 0018-5043

IS - 9

ER -