HYPOTENSIVE AND VASODILATOR ACTIONS OF SK&amp;F 24260, A NEW DIHYDROPYRIDINE DERIVATIVE

Fielden, R.; Owen, David A.; Taylor, E. M.

doi:10.1111/j.1476-5381.1974.tb08599.x

Cited by 23 publications

(9 citation statements)

References 11 publications

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“…Like hydralazine, SK&F 24260 has been described as a pre-capillary vasodilator (Fielden, Owen & Taylor, 1974). The present observations show that it causes a large fall in blood pressure, due to a decrease in total peripheral resistance with no change in cardiac output.…”

Section: Discussionsupporting

confidence: 51%

“…vasodilatation (Stunkard, Wertheimer & Redisch, 1954;Ablad, 1963) with those of SK&F 24260 (1,4 dihydro-2, 6-dimethyl-4-(2-trifluormethylphenyl)-3,5,-pyridinedicarboxylic acid diethyl ester) (Loev, Ehhreich & Tedeschi, 1972) with similar properties (Fielden, Owen & Taylor, 1974). Their circulatory effects are contrasted with those of the adrenergic neurone blocking drug, guanethidine.…”

Section: Introductionmentioning

confidence: 90%

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THE USE OF RADIOACTIVE MICROSPHERES TO COMPARE THE EFFECTS OF HYDRALAZINE, GUANETHIDINE AND SK&F 24260 ON THE REDISTRIBUTION OF CARDIAC OUTPUT IN ANAESTHETIZED RABBITS

Johnston

1975

British J Pharmacology

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IThe use of radioactive microspheres is described for the measurement of cardiac output in anaesthetized rabbits and its redistribution after the administration of drugs which lower blood pressure.2 Hydralazine increased peripheral vascular conductance by 123%. The vascular beds in which it had most effect were those of the carcass (mainly muscle) and the kidneys. 3 SK&F 24260,(1,4 dihydro-2, 6-dimethyl-4-(2-trifluormethylphenyl)-3,5,-pyridinedicarboxylic acid diethyl ester), had similar vasodilator actions. Its effect in the carcass contributed relatively more to the increase of total peripheral conductance. It also caused a remarkable degree of cerebral vasodilatation. 4 Guanethidine had a relatively small effect on total peripheral conductance and lowered blood pressure mainly by reducing stroke volume and cardiac output.

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Section: Discussionsupporting

confidence: 51%

Section: Introductionmentioning

confidence: 90%

THE USE OF RADIOACTIVE MICROSPHERES TO COMPARE THE EFFECTS OF HYDRALAZINE, GUANETHIDINE AND SK&F 24260 ON THE REDISTRIBUTION OF CARDIAC OUTPUT IN ANAESTHETIZED RABBITS

Johnston

1975

British J Pharmacology

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“…Alternatively, the increase in venous return due to the decreased venous resistance would be masked by the increased venous capacitance. The increase in venous return alone by SK&F 24260 can be well understood if one takes into account of the finding by Fielden et al (14) and by Johnston (24) that SK&F 24260 dilates preferentially precapillary sphincter vessels to reduce resistance but does little to capacitance vessels. Although the decreased venous return was a main feature of the effect of nitroglycerin, a transient but overt increase preceded the decrease.…”

Section: Discussionmentioning

confidence: 99%

“…In the present study in addition to nitroglycerin, 3 vasodilators, i.e., verapamil, trimetazidine, and 3,5-dicarbethoxy-2,6-dimethyl-4-(2-trifluoromethyl-phenyl)-1,4-dihydro pyridine (SK&F 24260) (13,14) were used, since in the previous studies (7,8) …”

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confidence: 99%

Differential effects of nitroglycerin, trimetazidine, verapamil and SK&F 24260 on venous return as revealed by the open-loop method in the dog.

1980

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Abstract-To obtain detailed information concerning the effects of different vaso dilators on venous return, experiments were carried out on 28 dogs by the use of the open-loop method. Blood from the superior and inferior venae cavae was drained at the level of the tricuspid valve into a reservoir, from which blood was pumped into the right atrium at a constant flow rate. Changes in reservoir volume reflected a total blood shift from the experimental dog and indicated changes in venous return. Drugs were administered into the ascending aorta. Nitroglycerin (1-10 pg/kg) decreased systemic blood pressure, total peripheral resistance and venous return but scarcely altered heart rate. Trimetazidine (0.3-3 mg/kg) decreased systemic blood pressure, total peripheral resistance, venous return and heart rate. Verapamil (10-100 ug/kg) decreased systemic blood pressure, total peripheral resistance and heart rate, and increased venous return. SK&F 24260 (1-10 fig/kg) decreased systemic blood pres sure, total peripheral resistance and increased venous return. Only high doses (10 30 pg/kg) of SK&F 24260 reduced heart rate. Rigorous measurements of systemic output showed that nitroglycerin (10 pg/kg), trimetazidine (3 mg/kg), verapamil (100 pg/kg), SK&F 24260 (10 pg/kg) produced no change in this parameter. SK&F 24260 increased venous return even when sino-aortic baroreceptor reflex was eliminated, ruling out reflex venoconstriction as a possible cause of the increased venous return. The results suggest the following: [1] Vasodilators like SK&F 24260 and verapamil increase venous return by decreasing arterial and/or venous resistance. [2] If the effect which increases venous capacitance prevails over the effect which decreases ar terial and/or venous resistance, venous return is reduced as is the case of nitroglycerin and trimetazidine.Nitroglycerin reduces the left ventricular end-diastolic pressure and volume (1-4), and such is considered to be one of mechanisms responsible for the antianginal action of nitro glycerin (1, 2, 4-6). The reduction in these 2 parameters is thought to be due mainly to a decrease in venous return (3, 4). Thus, it was of interest to investigate the effect on venous return of other vasodilators used for prevention of attacks of angina pectoris. In previous studies (7,8) we demonstrated that some of vasodilators increased venous return whereas others decreased it. However, in those studies we measured venous return by noncannulating type flow probes of electromagnetic flow meters placed at the superior and the inferior vena cava in anesthetized open-chest dogs and did not control cardiac input (the closed-loop method). Thus, it was hardly discernible whether the observed change in venous return by a certain vasodilator would be due to its effect on vasculature or on the heart. Most

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“…If this vasodilator action was selective for precapillary resistance vessels and the vasconstrictor action was not, then the resultant response would be selective constriction of post-capillary vessels. This seems unlikely, since in experiments using isovolaemic perfusion of the vascular bed of the cat intestine (Fielden, Owen & Taylor, 1974) McN-A-343 was equally effective in dilating both resistance and capacitance vessels (unpublished results).…”

Section: Effects Of Tilting Cats On Other Hypertensive Compoundsmentioning

confidence: 99%

EFFECT OF TILTING ON THE PRESSOR RESPONSES TO McN‐A‐343, A MUSCARINIC SYMPATHETIC GANGLION STIMULANT

Fielden¹,

Sutton²,

Taylor³

1980

British J Pharmacology

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1 In anaesthetized cats and dogs treated with mecamylamine, the pressor response to was increased when the animals were changed from a supine to a head-up, tilted position. This potentiation was not seen in rats. 2 The potentiation of the McN-A-343 pressor response was not affected by propranolol, destruction of the brain, or removal of the intestines, spleen or adrenal glands. It was promptly abolished by applying pressure to the lower half of the tilted animal. No increase in the pressor response to McN-A-343 occurred when cats were tilted head down. The potentiated response in tilted cats was abolished by atropine. 3 The pressor effects of adrenaline, noradrenaline, tryamine and angiotensin in cats treated with mecamylamine were either reduced or unchanged when the animal was changed from the supine to the tilted position. In one cat not treated with mecamylamine in which orthostatic hypotension occurred, tilting potentiated the pressor responses to dimethyl phenylpiperazinium iodide. 4 In cats anaesthetized with chloralose, the reflex pressor response to bilateral carotid occlusion was reduced by tilting. After mecamylamine treatment the residual atropine-sensitive response to carotid occlusion was potentiated when the animal was placed in the tilted position. 5 These results suggest that muscarinic stimulation of sympathetic ganglia by McN-A-343 raises blood pressure by predominantly reducing venous capacity, in contrast to noradrenaline and angiotension which increase blood pressure mainly by arterial vasoconstriction. 6 It is not clear whether this is a general property of sympathetic ganglionic stimulation or is restricted to stimulation of muscarinic sites.

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HYPOTENSIVE AND VASODILATOR ACTIONS OF SK&F 24260, A NEW DIHYDROPYRIDINE DERIVATIVE

Cited by 23 publications

References 11 publications

THE USE OF RADIOACTIVE MICROSPHERES TO COMPARE THE EFFECTS OF HYDRALAZINE, GUANETHIDINE AND SK&F 24260 ON THE REDISTRIBUTION OF CARDIAC OUTPUT IN ANAESTHETIZED RABBITS

THE USE OF RADIOACTIVE MICROSPHERES TO COMPARE THE EFFECTS OF HYDRALAZINE, GUANETHIDINE AND SK&F 24260 ON THE REDISTRIBUTION OF CARDIAC OUTPUT IN ANAESTHETIZED RABBITS

Differential effects of nitroglycerin, trimetazidine, verapamil and SK&F 24260 on venous return as revealed by the open-loop method in the dog.

EFFECT OF TILTING ON THE PRESSOR RESPONSES TO McN‐A‐343, A MUSCARINIC SYMPATHETIC GANGLION STIMULANT

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