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Biomedical subjects

O L Pedersen

Publications and source records attributed to O L Pedersen.

At least 73 records · Page 4Linked to original sources
PubMed1981

Comparative studies on the effects of tolmesoxide (Rx71107), a tolmesoxide metabolite (Rx71112) and nifedipine in isolated blood vessels.

1 The effect was studied of tolmesoxide (Rx71107), a tolmesoxide metabolite (Rx71112) and nifedipine on active tension in human isolated crural veins and in rat thoracic aorta. The effects of tolmesoxide and nifedipine on (22)Na and (45)Ca net influx in noradrenaline-induced contractions were investigated in rat thoracic aorta.2 Tolmesoxide, Rx71112 and nifedipine caused a concentration-related inhibition of noradrenaline (NA)- and potassium (K(+))-induced contractions in human veins. Nifedipine was by far the most potent drug in these respects. Tolmesoxide (4.7 muM-4700 muM) and Rx71112 (22 muM-220 muM) inhibited the NA-induced contraction more effectively than the K(+)-induced concentration. The reverse was true for nifedipine (0.0023-3 muM).3 Nifedipine had a similar potency in inhibiting the NA-induced contraction in rat aorta and human veins, whereas the inhibitory effect of tolmesoxide was more pronounced in rat aorta than in human veins.4 Tolmesoxide was a weak antagonist of the contractile effects of the cumulative addition of calcium on human veins. In concentrations up to 470 muM, tolmesoxide was completely devoid of inhibitory effects on (22)Na and (45)Ca net influx in rat aorta. Rx71112 (220 muM) had an inhibitory effect on (22)Na net influx but no significant effect on (45)Ca net influx.5 Nifedipine was an effective antagonist of the contractile effects of cumulative addition of calcium in human veins and had a concentration-related inhibitory effect on both (22)Na and (45)Ca uptake in rat aorta.6 The results indicate that tolmesoxide and Rx71112 cause dilatation of human crural veins in vitro at concentrations that do not interfere with the net transmembranal movements of Ca and are thus clearly different from the effects of nifedipine.

Adult↗
PubMed1981

Effects of ergotamine on isolated human vessels.

In isolated human mesenteric and crural veins, ergotamine induced long-lasting contractions. These contractions were resistant to repeated wash-out and were not affected by alpha-adrenoceptor blockade, but could be abolished by removal of extracellular calcium or by the presence of the calcium-blocker nifedipine. In contrast to its effect on human mesenteric and crural veins, ergotamine had no contractile effect, but a marked relaxant effect on mesenteric arteries mediated via blockade of alpha-receptors. The ergotamine-induced contraction was not affected by indomethacin (0.28--2.8 microM) nor was it influenced by serotonin (5-HT). In both mesenteric and crural veins, the ergotamine-induced contraction was diminished by the 5-HT blocking agent, methysergide. In veins, development of tachyphylaxis to 5-HT was demonstrated. It is concluded that ergotamine has a direct contractile effect on isolated human mesenteric and crural veins. These effects are dependent on unhindered influx of extracellular calcium and are at least partly mediated via 5-HT receptors. In mesenteric arteries, ergotamine acted as an alpha-adrenoceptor blocker, and had no contractant effect.

Adult↗
PubMed1979

Effect of nifedipine on plasma renin, aldosterone and catecholamines in arterial hypertension.

Acute sublingual administration of nifedipine 10--20 mg to 13 hypertensive patients caused a rapid decrease in blood pressure (BP) and a concomitant increase in heart rate (HR), plasma noradrenaline (NA) and plasma renin activity (PRA); there was no significant change in plasma adrenaline (A) or aldosterone (ALDO). Basal PRA was the major determinant of the rise in PRA, as a close correlation was present between the basal value and the increase caused by nifedipine (r = 0.92), p less than 0.001). The rise in PRA was also correlated with the plasma concentration of nifedipine after 60 min (r = 0.80, p less than 0.01), but it was not correlated with the decrease in BP, the rise in HR or the increase in NA. Nifedipine 30--60 mg daily for 6 weeks caused a reduction in mean BP from 133 to 113 mmHg (p less than 0.001). Body weight and serum potassium decreased but no consistent change was noted in NA, PRA, ALDO or 24 h-excretion of catecholamines. A significant correlation was present between the change in NA and that in PRA (r = 0.74, p less than 0.01). The alterations in the various parameters in the acute and chronic studies were not correlated. The findings indicate that different regulatory mechanisms are activated during acute and chronic administration of nifedipine. It is suggested that an initial rise in sympathetic activity gradually decreases during prolonged therapy, but it still remains a determinant of PRA.

Adult↗
PubMed1979

Serum potassium and uric acid changes during treatment with timolol alone and in combination with a diuretic.

Timolol, 10 to 40 mg daily, given to 103 patients with uncomplicated arterial hypertension induced significant increments of serum potassium at all dose levels (p less than 0.05). The magnitude of the increments was dependent on daily timolol dosage. When hydrochlorothiazide and amiloride were added, serum potassium decreased (p less than 0.001), but a major determinant of the magnitude of the decrease was the dosage change of the timolol. Serum uric acid was influenced in a paradoxical way during timolol monotherapy; there was a rise in all 3 dosage groups (p less than 0.02) but the lowest group showed the largest increase and vice versa. On addition of hydrochlorothiazide and amiloride, there was a further increase in serum uric acid, the magnitude of which depended on the concomitant reduction in the dose of timolol, with reductions in dose causing a larger rise in serum uric acid and increments, a smaller rise. The increments of serum uric acid were greater in females than in males during both treatment periods. The results indicate that beta blockers induce dose-dependent rises in serum potassium and may counteract undesirable effects of diuretics on serum potassium. Beta blockers seem to have a paradoxical effect on serum uric acid and may aggravate the hyperuricemia induced by diuretics.

Amiloride↗
PubMed1979

Individual factors influencing the response to a beta-adrenergic blocking agent given alone and in combination with a diuretic on arterial hypertension.

103 patients with arterial hypertension were treated with timolol + placebo for 7 weeks in a multicentre trial, and with timolol + hydrochlorothiazide and amiloride for a further 7-week period. The decrease in blood pressure (BP) produced by timolol alone was influenced neither by the dose of timolol, initial heart rate, magnitude of pretreatment BP nor by age. 64% of the patients less than 40 years of ages, and 48% of the older patients, were well regulated on beta-blocker monotherapy. When the diuretic was given in addition, the BP response in the older age group improved, whereas younger patients showed no change. A significant correlation was found between age or magnitude of untreated BP and the decrease in BP caused by the diuretic. The cardiothoracic ratio increased significantly on timolol alone, whereas no change was found on the combined therapy. Weight changes in the two different treatment periods showed a significant correlation, but they were not related to the observed reduction in BP. The results suggest that in younger patients, beta-blocker therapy is just as effective as a combined treatment with a diuretic, whereas in older patients considerably better regulation is achieved by combined therapy.

Adult↗
PubMed1979

Effects of digoxin on islated human mesenteric vessels.

Digoxin had contractant effects on isolated, human mesenteric arteries and veins. Veins were more sensitive to this action of the glycoside than arteries. The contractions were not affected by phentolamine or by washing with a digoxin-free solution. However, they were abolished by the calcium antagonist nifedipine, and by washing with a calcium-free medium. In the presence of digoxin, the maximum response to noradrenaline (1.8 x 10(-5) M) increased markedly in both arteries and veins, and the concentration-response curve for the amine was displaced to the left. Immersion of vein preparations in calcium-free solution for 30 min. abolished the digoxin contracture; an increase in extracellular calcium restored the response. Changes in extracellular potassium concentration caused changes in tension in tension of the mesenteric veins similar to those previously demonstrated in peripheral veins--both in the presence and in the absence of digoxin. It is concluded that digoxin contracts mesenteric vessels by a direct action on the muscle cells, and potentiates the contractant effects of noradrenaline. These effects are dependent on the availability of extracellular calcium. Mesenteric vascular reactions caused by changes in extracellular potassium are influenced by digoxin.

Aged↗
PubMed1979

Effects of digoxin on isolated human peripheral arteries and veins.

In isolated human crural arteries and veins, digoxin induced slowly developing, long-lasting contractions. These contractions were not diminished by alpha-adrenoceptor blockade or by washing, but were abolished by the calcium antagonist nifedipine. In the presence of digoxin, the maximum contractile responses to noradrenaline (18 microM) and potassium (127 mM) markedly increased, and the glycoside shifted the noradrenaline concentration-response curve to the left. Immersion of vein preparations in calcium-free medium for 30 min. abolished the digoxin contraction, whereas responses could still be elicited by potassium and noradrenaline. A change of the extracellular potassium concentration from 4.6 to 6.9 and 9.2 mM caused relaxation, and a further increase to 13.8 mM contracted the preparations. After pretreatment with digoxin (1 micronM), a potassium change from 4.6 to 1.15 mM caused relaxation and all concentrations exceeding 4.6 mM produced contraction. It is concluded that digoxin has a direct contractile effect on isolated human crural vessels, and that this effect is dependent on the extracellular calcium concentration. In the presence of the glycoside, the responses to noradrenaline and potassium are potentiated. Vascular responses to changes in extracellular potassium concentration are influenced by digoxin.

Adolescent↗
PubMed1979

Comparison of the in vitro effects of prazosin, nifedipine, and dihydralazine in isolated human mesenteric and crural vessels.

The inhibitory and relaxing effects of prazosin, nifedipine, and dihydralazine on contractions induced by noradrenaline (NA), or potassium (K+), were investigated in isolated human crural and mesenteric arteries and veins. Vascular ring preparations were suspended in organ baths and isometric tension was recorded. Prazosin was the most potent of the drugs in counteracting NA-induced contractions in all types of vessels except crural veins, in which the effect of nifedipine was the more pronounced. On K+-induced contractions prazosin was completely devoid of relaxing or inhibitory effects, whereas nifedipine was by far the most effective of the investigated drugs. Nifedipine had a more marked effect in venous than in arterial preparations from the peripheral circulation, but no such difference was seen in mesenteric vessels. Dihydralazine was found to have a very low potency in all types of vessels, and no difference between the effects on arterial and venous preparations was found. The results suggest that the in vitro effects of prazosin, nifedpine, and dihydralazine are different from those observed in vivo. Thus, the balance between the effects on arteries and veins in vitro was quite different from those reported in clinical studies on the three vasodilatators. The results give no support to the hypothesis of an unspecific vasodilatating effect of prazosin. The clinical usefulness of dihydralazine cannot be explained from the poor in vitro effects of the unmetabolized drug.

Adolescent↗
PubMed1978

Does verapamil have a clinically significant antihypertensive effect?

Verapamil was evaluated as an antihypertensive agent in a pilot study. Intravenous administration of 0.1 mg/kg, followed by constant infusion of 0.0035 mg/kg min, reduced both systolic and diastolic blood pressure significantly; the maximal average decrease of 23/16 mm Hg occurred after 5 min. The resting pulse rate rose during infusion and prolongation of the atrio-ventricular conduction time was a constant finding. After the initial drop in blood pressure, a rise toward control levels was observed, despite an increase in the infusion rate. Five patients received oral treatment with verapamil 320-640 mg daily for 7 weeks. In four of the five patients a blood pressure reduction was obtained (mean: 14/12 mm Hg), but normotension was not achieved in any of them. In contrast to the acute studies, the atrio-ventricular conduction time showed no change and a decrease in resting pulse rate was noted. Two patients experienced sensations of heat and reddening of face during treatment. It is concluded that verapamil has a rather modest antihypertensive effect and it is not suitable for the treatment of arterial hypertension.

Administration, Oral↗