Diminished vasodilation; imbalance of synthesized cyclooxygenase products by adrenergic mediation in diabetic coronaries of the dog.
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Animals↗
Biomedical subjects
M Z Koltai
Publications and source records attributed to M Z Koltai.
Effects of first and second generation sulphonylureas on cardiotoxicity of strophanthidin in rabbits.
The effects of the first generation sulphonylurea compound gliclazide and the second generation sulphonylurea compound glipizide on strophanthidin toxicity was investigated in rabbits. The sulphonylurea pretreated animals were intravenously infused with 23 mumol/kg strophanthidin until the appearance of the first ventricular ectopic beat and continued thereafter until the appearance of ventricular fibrillation. The first generation sulphonylurea gliclazide increased, while the second generation sulphonylurea glipizide decreased the strophanthidin toxicity in a dose dependent manner. It was concluded that instead of first generation sulphonylureas, second generation sulphonylureas must be preferred in cardiac glycoside treated diabetics, when sulphonylurea treatment is necessary.
Animals↗
Relationship between vascular adrenergic receptors and prostaglandin biosyntheses in canine diabetic coronary arteries.
Before the onset of histologically detectable alterations of diabetic arteries, a considerable decrease of vasodilation ability develops. The role of an altered prostaglandin biosynthesis in this phenomenon was investigated in connection to the altered vascular adrenergic mechanisms. The effect of phenylephrine on prostacyclin production of isolated coronary arterial rings (100 mumol/l) as well as on conductivity of the coronary arterial bed (7.5-15-30-60 pmol. kg-1.min-1) were compared in 12 metabolically healthy and 12 alloxan-diabetic (560 mumol/kg) dogs. Furthermore, the effect of phentolamine (5 mumol/l) on the prostacyclin and thromboxane productions of the isolated vessels (coronary, femoral and basilar arteries) was investigated by radioimmunoassay. Although the basal prostacyclin amounts synthesized by healthy and diabetic coronary vessels were not different (5.1 +/- 1.6 and 4.9 +/- 1.4 pg/mg vessel/30 min), similarly to femoral and basilar arteries, the diabetic arterial rings produced significantly (p less than 0.05) more thromboxane than the control rings. The alpha-adrenergic blockade by phentolamine did not influence the prostacyclin production in the healthy arteries, but considerably (p less than 0.05) increased it in the diabetic coronary arteries. Phentolamine normalised the thromboxane synthesis in the diabetic group (p less than 0.01) and enhanced (p less than 0.05) it in the metabolically healthy group. Phenylephrine was ineffective (98 +/- 6%) on the prostacyclin production in vitro versus the stimulated (150 +/- 22%) prostacyclin synthesis detected in the metabolically healthy group; and in vivo induced a more significant (p less than 0.05) decrease in the coronary conductivity in diabetic than in control groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Influence of experimental diabetes on the mechanical responses of canine coronary arteries: role of endothelium.
The influence of experimental diabetes on the endothelium mediated relaxation and contractile responses of canine isolated coronary arteries was studied in arteries removed from alloxan treated diabetic (280 mmol.kg-1) and control mongrel dogs. Strips with and without endothelium were suspended in Krebs bicarbonate solution for isometric recording. Relaxation responses to acetylcholine (1.8 X 10(-8) to 9.4 X 10(-6) mol.litre-1, A23187 (10(-8) to 1.28 X 10(-6) mol.litre-1), and sodium nitroprusside (10(-9) to 10(-7) mol.litre-1) as well as contractile responses to prostaglandin F2 alpha, (1.7 X 10(-7) to 5.6 X 10(-4) mol.litre-1) were determined. In all intact strips acetylcholine, and A23187 induced similar concentration dependent reduction of the prostaglandin F2 alpha (2 X 10(-6) mol.litre-1) evoked tone. No significant difference was observed between sodium nitroprusside evoked relaxations of normal and diabetic arteries. Cyclooxygenase blockade reduced the maximal relaxations induced by acetylcholine and A23187 in diabetic vessels, whereas it did not change the endothelium dependent relaxation of normal arteries. Diabetes increased significantly the sensitivity to acetylcholine (EC50 4.1(0.4) X 10(-7) mol.litre-1 in control and 6(0.7) X 10(-8) mol.litre-1 in diabetic arteries; p less than 0.01, n = 7) and to A23187 (EC50: 7(1) X 10(-8) mol.litre-1 in control and 3.8(0.3) X 10(-8) mol.litre-1 in diabetic vessels; p less than 0.01, n = 7); in contrast, prostaglandin F2 alpha remained an equiactive constrictor in normal and diabetic vessels with intact endothelium.(ABSTRACT TRUNCATED AT 250 WORDS)
Acetylcholine↗
Insulin induced reversibility of altered responsiveness in femoral arterial bed of diabetic dogs.
The altered reactivities of femoral arterial bed to noradrenaline, phenylephrine, adenosine and prostacyclin were compared in 18, clinically manifest but aketotic, alloxan diabetic mongrel dogs. Alloxan treatment markedly increased the vasoconstrictor responses to noradrenaline and phenylephrine, as well as the adenosine-induced vasodilation in the femoral vasculature. These changes were prevented or normalized, respectively, in the early or late insulin-treated alloxan diabetic animals. In the case of noradrenaline not only a normalization but also an explicit overcompensation could be observed by insulin treatment. The altered reactivity to prostacyclin could not be influenced by insulin therapy. These results indicate a significant difference in the effect of insulin treatment on the altered diabetic vascular responsiveness to catecholamines and adenosine or to prostacyclin.
Animals↗
Influence of diabetic state on coronary vasoregulation in myocardial hypoxia.
It is a matter of common knowledge that under ischaemic or hypoxic conditions the oxygen demand of the myocardium could only be satisfied by enhancement of collateral blood flow. It is demonstrated that in a diabetic state an elevation of the myocardial blood flow could not develop due to lack of proper vasodilation in the coronary arterial bed.
Animals↗
Prostaglandins and altered diabetic vasoregulation.
In previous studies an enhanced tendency to vasconstriction could be demonstrated in special regions, first of all in the coronary arterial bed of the diabetic vasculature. Analysing the role of prostaglandins in this phenomenon, the present work demonstrates that in vivo the dose-dependent decrease in the conductivity of the coronary arterial bed induced by PGF2 alpha (3, 6, 12, 24, 48 nmol/kg) administration in alloxan- (560 mumol/kg) diabetic dogs (n = 6) proved to be more expressed after indomethacin (10 mumol/kg) treatment compared with metabolically healthy (n = 6) animals. In the presence of indomethacin (3 mumol/l) PGF2 alpha (1, 3, 10, 30 mumol/l) evoked also considerably higher vasoconstriction in the isolated coronary rings of the diabetic dogs in comparison to the metabolically healthy state. The data are referring to the contribution of an altered prostaglandin biosynthesis in the diabetic coronaries to their increased tendency to vasoconstriction induced by PGF2 alpha.
Animals↗
Contractile and relaxant responses of diabetic dog femoral arteries.
Strips of femoral arteries of normal and alloxan-treated dogs were set up for isometric recording. The contractile response to phenylephrine and the relaxant response to acetylcholine were determined. Neither alloxan treatment nor mechanical removal of endothelium altered the EC50 value for phenylephrine. The slope of phenylephrine dose-response curves of diabetic and healthy vessels with intact endothelium was similar, whereas the slope of phenylephrine dose-response curves of endothelium-denuded diabetic arteries was significantly greater than that of the denuded healthy arteries. Removal of the endothelium completely abolished the relaxant effect of acetylcholine. The relaxant potency (IC50) of acetylcholine was not affected by alloxan treatment. The results suggest that in canine femoral arteries the relaxant activity of acetylcholine is unaffected in experimental diabetes and the damage of the arterial endothelium may play a role in the increased responsiveness of diabetic vessels to adrenergic agonists.
Acetylcholine↗
Ultrastructural alterations in cardiac and skeletal muscles in experimental diabetes mellitus.
In 18 alloxan-diabetic and 12 metabolically healthy dogs cardiac and skeletal muscles have been studied electronmicroscopically. Myopathy-like alterations, as widening of Z band material, alterations of mitochondria as well as of collagen fibers were observed in the diabetic myocardium. In skeletal muscle nemalin bodies were found. These latter alterations don't develop in insulin-treated diabetic state.
Animals↗
Left ventricular diastolic function in diabetics.
Left ventricular diastolic function was studied in 29 young diabetic patients (aged from 14 to 44 years) without any clinical sign of heart disease. The metabolic state, the presence and the degree of microvascular and neuropathic complications have been established. Age and sex matched 32 healthy subjects served as controls. The parameters of left ventricular diastolic function were determined by means of phonomechanocardiography. By this method in diabetic patients impaired diastolic function of the left ventricle was found. This alteration could be best characterized by the values of normalized relaxation index referring to the isovolumetric relaxation of the left ventricle. A close correlation was found between the microvascular and neuropathic complications and the left ventricular diastolic dysfunction, while no correlation could be demonstrated between the metabolic state and the diastolic cardiac disorder.
Adult↗
The effect of various hypoglycaemic sulphonylureas on the cardiotoxicity of glycosides and arrhythmogenic activity due to myocardial ischaemia.
The effects of different sulphonylureas on the electrical cardiac activity were studied in 145 rabbits and in 103 rats as well as in 278 digitalis-treated, non-smoker non-insulin-dependent diabetics on the same therapy at least during the previous three months. In rabbits and rats glibenclamide (0.0032-100 mumol. kg-1) decreased, while tolbutamide and carbutamide (0.008-1000 mumol. kg-1) increased strophantidin toxicity and myocardial ischaemia induced transitory ventricular fibrillation dose-dependently. The differences between the dose-response curve of glibenclamide and those of tolbutamide or carbutamide were significant. In digitalized non-insulin-dependent diabetics, multifocal ectopic ventricular beats could be observed in none among the 80 glibenclamide-treated diabetics, while in 12 cases of the 71 tolbutamide and in 10 cases of the 61 carbutamide treated diabetics. Two of the 66 non-insulin-dependent diabetics receiving only diet and 7 of the 278 age and sex matched, non-smoker, metabolically healthy patients had multifocal ectopic ventricular beats. No significant difference could be found between the therapeutical groups. It was concluded that instead of tolbutamide, glibenclamide must be preferred in digitalis-treated diabetics, when metabolic control is not satisfactorily achieved by diet and regime alone.
Animals↗
Differential contractile responsiveness of femoral arteries from healthy and diabetic dogs: role of endothelium.
Phenylephrine-induced contraction and acetylcholine-induced relaxation of isolated femoral arterial strips (with and without endothelium) of diabetic (alloxan-treated) and metabolically healthy dogs were determined. Alloxan treatment did not change the contractile responsiveness to phenylephrine (PE) of the arteries with intact endothelium. After mechanical removal of the endothelial layer, however, the maximum force generated by the diabetic vessels (22.0 +/- 2.0 mN.m-2) significantly exceeded the maximum contraction produced by the nondiabetic arteries (14.6 +/- 1.8 mN.m-2). The dose-response curve of diabetic arteries to PE was steeper than it was in non-diabetic strips. The EC50 values for PE were similar in these two groups (0.45 +/- 0.12 and 0.58 +/- 0.20 mumol/l in diabetic and nondiabetic vessels, respectively). In the arteries with intact endothelium, acetylcholine produced concentration-related reduction of PE-induced tone. This endothelium-dependent relaxant activity of acetylcholine was similar in the healthy and diabetic arterial strips, IC50 for acetylcholine being 0.17 +/- 0.02 and 0.20 +/- 0.03 mumol/l, respectively. These results suggest that functional alteration of endothelium (probably an increased release of EDRF) prevails in diabetes. This may be important in reducing the hyper-responsiveness of diabetic arterial smooth muscle to PE.
Animals↗
Functional and morphological investigations of the heart in acute experimental hypoxia.
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Acute Disease↗
Direct cardiac effects of an ionic and a non-ionic contrast medium in dogs.
Direct cardiac effects of ionic diatrizoate (Uromiro) and non-ionic iopamidol (Iopamiro) were investigated in "in situ" heart-lung preparation of 19 vagotomized dogs. Diatrizoate was found to induce considerably greater alteration in plasma osmolality and subsequent dehydration of the myocardium compared with iopamidol. Myocardial dehydration resulted in a decrease of left ventricular compliance and in that of cardiac performance. Diatrizoate was shown to influence the myocardium not only by its hyperosmolarity but also by a direct action. Heart rate was reduced by both contrast media.
Animals↗
Effects of various hypoglycaemic sulphonylureas on the cardiotoxicity of glycosides.
In diabetic patients it has been shown that tolbutamide and carbutamide enhanced and glibenclamide did not influence the incidence of digitalis intoxication, or that of multifocal ectopic beats or coupling due to premature ectopic ventricular beats during digitalis therapy. In rabbits glibenclamide decreased and tolbutamide and carbutamide increased strophanthidin toxicity in a dose dependent manner. It was concluded that glibenclamide should be preferred to tolbutamide or carbutamide in digitalis-treated diabetics, when satisfactorily metabolic control is not achieved with a dietary regime alone.
Aged↗
Comments on "Myocardial micronecrosis produced by microsphere embolization: role of an alpha-adrenergic tonic influence on the coronary microcirculation".
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Adrenergic alpha-Agonists↗
Diabetic myocardial alterations in ultrastructure and function.
Myocardial samples taken from six healthy and six alloxan-diabetic dogs by means of percutaneous needle-biopsy were investigated electronmicroscopically. Specific increase in the number of collagen fibers and that of mitochondria were demonstrated beside the widening of Z bands. In the same experimental animals, a close, inverse correlation was detected (y = 0.0068x + 0.1680; r = 0.8648; F = 29.6705; n = 12) between the values of the left ventricular passive elastic modulus and those of the plasma glucose disappearance rate determined immediately before the haemodynamic investigation. On the basis of the ultrastructural findings, the proliferation of collagen fibers can be made also responsible for functional disorder of the diabetic myocardium.
Animals↗
Effects of cyclooxygenase inhibitors, prostaglandins F2 alpha and I2, on isolated coeliac and basilar arteries of alloxan-diabetic dogs.
The effects of prostaglandin synthetase inhibitors PGF2 alpha and PGI2 on the tone of isolated basilar and coeliac arteries were studied in healthy and alloxan-diabetic dogs. PGF2 alpha (1 mumol 1-1) produced a significantly higher tone in diabetic basilar arteries (1.15 +/- 0.16 mN) than in normal cerebral vessels (0.7 +/- 0.10 mN). By contrast, the contractile responses of normal and diabetic coeliac arteries to PGF2 alpha did not differ. The cyclooxygenase inhibitors indomethacin (3 mumol 1-1) and suprofen (0.58 mumol 1-1) potentiated the PGF2 alpha-evoked contractions in all of the vessels studied. The percent potentiation was greater (50-60%) in the basilar arteries from alloxan-treated dogs than in normal basilar vessels (22-30%). There was not such a difference between diabetic and normal coeliac arteries. Prostacyclin produced a concentration-related relaxation in the presence of indomethacin or indomethacin + PGF2 alpha. The relaxant potencies of PGI2 were similar in the vessels from metabolically healthy and diabetic dogs. The IC50 values for PGI2 were 11.6 +/- 1.3 and 11.8 +/- 1.8 nmol 1-1 in normal and diabetic basilar arteries, respectively; they were 25.4 +/- 3.2 and 26.2 +/- 3.9 nmol 1-1 in control and alloxan-treated coeliac vessels. These results indicate that normal and diabetic vessels may have differential reactivity to cyclooxygenase inhibitors, this difference being dependent on the vascular region.
Animals↗