The direct effect of hypoglycaemic sulphonylureas on myocardial contractile force and arterial blood pressure

Pogátsa, G; E, Dubecz

doi:10.1007/bf01234506

Cited by 22 publications

(6 citation statements)

References 16 publications

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“…Intravenous administration of tolbutamide (Karnafel & Figueroa 1978), carbutamide or gliclazide (Pogatsa & Dubecz 1977) to dogs caused positive inotropic and blood-pressure-enhancing effects. Intravenous administration of tolbutamide (Karnafel & Figueroa 1978), carbutamide or gliclazide (Pogatsa & Dubecz 1977) to dogs caused positive inotropic and blood-pressure-enhancing effects.…”

Section: Animal Studiesmentioning

confidence: 99%

“…Intravenous administration of tolbutamide (Karnafel & Figueroa 1978), carbutamide or gliclazide (Pogatsa & Dubecz 1977) to dogs caused positive inotropic and blood-pressure-enhancing effects. In one study gliclazide and carbutamide also had an inotropic effect on pancreatectomised and adrenalectomised dogs, which would support the view of a direct cardiac effect of the sulphonylureas (Pogatsa & Dubecz 1977). Furthermore, there was an accumulation of triglycerides in the myocardium in both tolbutamide-and diet-treated non-diabetic dogs; the effect was greatest in tolbutamide-treated diabetic dogs.…”

Section: Animal Studiesmentioning

confidence: 99%

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Adverse Cardiovascular Effects of Sulphonylurea Drugs

Huupponen

1987

Medical Toxicology

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Sulphonylureas are widely used in the treatment of diabetes mellitus. Since the publication of the University Groups Diabetes Program (UGDP) results the discussion on their possible cardiovascular side effects has been lively and sometimes even passionate. The initial UGDP findings about the adverse effects of tolbutamide on the cardiovascular system have been criticised, particularly for shortcomings in the study design. The results of other epidemiological studies of the sulphonylurea effects on cardiovascular morbidity and mortality published this far have been contradictory. This is understandable because the factors involved are very complex. Most of these studies have used tolbutamide only, and the findings cannot necessarily be directly extrapolated to other sulphonylureas. Only properly performed prospective studies may provide further information on this issue. High concentrations of several sulphonylureas may have inotropic effects on heart muscle in in vitro animal models, but human studies performed in vivo do not support the view of clinically significant inotropy for sulphonylureas. High concentrations of tolbutamide or glibenclamide (glyburide) may affect the myocardial metabolism in isolated organs, but the possible clinical significance of these findings remains unknown. Some epidemiological and experimental studies have associated oral antidiabetic treatment with the occurrence of cardiac arrhythmias or increased digitalis toxicity. Only a few results are available, and there may be differences between the sulphonylureas in this respect. Antiaggregatory properties have been postulated for some sulphonylureas. Gliclazide, in particular, has been studied, but some other compounds of this class have also been effective in short term studies. If confirmed, these effects on haemostasis would be noteworthy. The sulphonylurea effects on serum lipids, especially on HDL-cholesterol, have been discussed widely during the last few years. Decreases in HDL-cholesterol concentrations were suggested to be associated with sulphonylurea therapy. However, these findings were not confirmed in recent cross-sectional and longitudinal studies performed with different sulphonylureas. Chlorpropamide, and to a lesser extent tolbutamide, may cause dilutional hyponatraemia and aggravate existing heart failure. Glibenclamide may increase the clearance of water in the kidney.

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“…Intravenous administration of tolbutamide (Karnafel & Figueroa 1978), carbutamide or gliclazide (Pogatsa & Dubecz 1977) to dogs caused positive inotropic and blood-pressure-enhancing effects. Intravenous administration of tolbutamide (Karnafel & Figueroa 1978), carbutamide or gliclazide (Pogatsa & Dubecz 1977) to dogs caused positive inotropic and blood-pressure-enhancing effects.…”

Section: Animal Studiesmentioning

confidence: 99%

“…Intravenous administration of tolbutamide (Karnafel & Figueroa 1978), carbutamide or gliclazide (Pogatsa & Dubecz 1977) to dogs caused positive inotropic and blood-pressure-enhancing effects. In one study gliclazide and carbutamide also had an inotropic effect on pancreatectomised and adrenalectomised dogs, which would support the view of a direct cardiac effect of the sulphonylureas (Pogatsa & Dubecz 1977). Furthermore, there was an accumulation of triglycerides in the myocardium in both tolbutamide-and diet-treated non-diabetic dogs; the effect was greatest in tolbutamide-treated diabetic dogs.…”

Section: Animal Studiesmentioning

confidence: 99%

Adverse Cardiovascular Effects of Sulphonylurea Drugs

Huupponen

1987

Medical Toxicology

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“…116±14 (8) 299±31 (8) 260±43 (8) Male Control 61±15(7)t 133±10(8)t 280±39 (8) 235±4O (7) rats Glyburide 55 + 12 (8) 130±ll (8) 306±39 (8) 220 ±49 (8) Values are mean±SEM. Number of rats per group shown in parentheses.…”

Section: Resultsmentioning

confidence: 99%

“…57 Glyburide (a secondgeneration sulfonylurea antidiabetic agent) has been reported to decrease blood pressure when administered acutely to normal male and female dogs. 8 - 9 Sulfonylurea agents are insulin secretagogues 10 but have also been reported to sensitize peripheral tissues to insulin actions. 11 ' 12 We sought to determine if long-term administration of glyburide would lower blood pressure in the combined form of salt-sensitive and spontaneous hypertension bred into the stroke-prone spontaneously hyper-tensive rat (SHRSP).…”

Section: Sex-specific Effects Of An Insulin Secretagogue In Stroke-prmentioning

confidence: 99%

Sex-specific effects of an insulin secretagogue in stroke-prone hypertensive rats.

et al. 1993

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Glyburide, an insulin secretagogue and an insulin-sensitizing agent, lowers blood pressure in normal male and female dogs when administered acutely. Because insulin resistance may contribute to spontaneous hypertension in rats, we sought to determine if long-term administration of glyburide (5 mg/kg per day by diet, age 5 weeks to 5 months) would lower blood pressure in male and female stroke-prone spontaneously hypertensive rats. Arterial (aortic) rings from these rats were incubated with insulin in vitro (100 mU/mL) 1 hour before and during phenylephrine-induced contraction to determine if long-term glyburide administration improves vascular sensitivity to the intrinsic vasodilator action of insulin. Glyburide, however, significantly increased blood pressures and ratios of heart weight to body weight in 5 -month-old female rats (+20 mm Hg diastolic, P<.05), with no significant change noted in male rats (+4 mm Hg diastolic). Glyburide increased plasma insulin levels (twofold, P<.04) in female but not in male rats. Glyburide did not affect plasma glucose or catecholamine levels. After incubation with insulin, aortic rings from glyburide-treated female rats demonstrated more than 40% greater contractile responsiveness to phenylephrine compared with aortic rings from control female rats (/*<.O4). This insulin-dependent increase in phenylephrine-induced contraction consisted of a reversal in the in vitro action of insulin, from attenuation to accentuation of such contraction (P<.05). This change was not seen in male rats. Neither gender, glyburide, nor insulin influenced acetylcholine-induced relaxation of phenylephrineinduced contraction. Insulin in vitro slightly increased nitroprusside-induced relaxation (P<.05) of aortic rings from female but not from male rats, and glyburide administration abolished this increase. Thus, long-term glyburide administration aggravates hypertension selectively in female stroke-prone spontaneously hypertensive rats. This aggravation may be due to a sustained increase in circulating insulin accompanied by emergence of a paradoxical vasoconstrictor sensitivity to insulin in vascular smooth muscle. (Hypertension 1993^2:214-220) KEY WORDS • vascular resistance • insulin • sulfonylurea compounds • catecholamines • glucose • gender T here is considerable evidence that the insulin resistance and hyperinsulinemia of diabetes also exists in essential hypertension 1 and in various genetic models of hypertension such as Zucker obese, Dahl salt-sensitive, and spontaneously hypertensive rats (SHR).2 -4 Recently, two separate classes of antidiabetic, insulin-sensitizing agents (biguanides and thiazolidinediones) were reported to attenuate hypertension in these animal models.57 Glyburide (a secondgeneration sulfonylurea antidiabetic agent) has been reported to decrease blood pressure when administered acutely to normal male and female dogs. 8 -9 Sulfonylurea agents are insulin secretagogues 10 but have also been reported to sensitize peripheral tissues to insulin actions.11 ' 12 We sought to de...

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“…As distinct from two previous studies (29,30), all of our patients were on diet therapy only. Thus the possible effects of insulin on cardiovascular reflexes (35) and of sulphonylureas on left ventricular function (36,37) were ruled out. In addition, we did not exclude patients with evident heart disease at the initial examination.…”

Section: Systolic Time Intervals Blood Pressure and Heart Ratementioning

confidence: 99%

Effect of Correction of Hyperglycemia on Left Ventricular Function in Non‐Insulin‐Dependent (Type 2) Diabetics

Uusitupa

Siitonen

Aro

et al. 1983

Journal of Internal Medicine

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Systolic time intervals (STI) were recorded in 33 newly diagnosed non‐insulin‐dependent diabetics (19 men, 14 women, aged 44–64 years) before and after 3–8 months' dietary therapy. The mean (±SD) fasting blood glucose was 11.1±2.6 mmol/l before treatment and 7.8±1.8 at the second examination (p<0.001). Concomitantly with the decline in blood glucose concentration, the heart rate corrected pre‐ejection period (PEP) decreased from 139±11.9 to 135±14.4 msec (mean±SD) (p<0.05), the heart rate corrected left ventricular ejection time (LVET) increased from 400 ± 15.1 to 410±20.7 msec (p<0.0025) and the PEP/LVET ratio decreased from 0.39±0.06 to 0.36±0.06 (p<0.005). When the diabetics were divided into two groups according to the degree of the decline in blood glucose concentration, only those whose fasting blood glucose decreased by ≥3 mmol/l showed significant changes in STI. No significant changes were observed in the mean heart rate or systolic blood pressure during the treatment. Cardiac dysfunction occurring in untreated non‐insulin‐dependent diabetics may be caused by metabolic factors and it may be reversed at least partially by correction of hyperglycemia.

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The direct effect of hypoglycaemic sulphonylureas on myocardial contractile force and arterial blood pressure

Cited by 22 publications

References 16 publications

Adverse Cardiovascular Effects of Sulphonylurea Drugs

Adverse Cardiovascular Effects of Sulphonylurea Drugs

Sex-specific effects of an insulin secretagogue in stroke-prone hypertensive rats.

Effect of Correction of Hyperglycemia on Left Ventricular Function in Non‐Insulin‐Dependent (Type 2) Diabetics

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