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Biomedical subjects

E Mikkelsen

Publications and source records attributed to E Mikkelsen.

At least 19 recordsLinked to original sources
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

Abrupt withdrawal of beta-blocking agents in patients with arterial hypertension. Effect on blood pressure, heart rate and plasma catecholamines and prolactin.

Chronic treatment with beta-blockers was interrupted abruptly in six patients with arterial hypertension. Three patients, who had experienced symptoms during a previous withdrawal, again complained of transient palpitations, tremor, sweating, headache and general malaise. A significant increase in standing blood pressure (BP) and heart rate (HR) was noted after 24 h. The standing HR reached a maximum after 48 h and had decreased significantly on the 7th day (p less than 0.005). There was a strong tendency to greater increase in standing BP and HR in the patients who experienced symptoms than in those who did not. Plasma concentrations of noradrenaline, adrenaline and prolactin did not change significantly. Thus, beta-blocker withdrawal symptoms are reproducible and are indicative of a transient sympathetic hyperresponse. The increased activity is not likely to be caused by increased production of circulating catecholamines, but rather by increased sensitivity of the beta-receptor.

Adrenergic beta-Antagonists↗
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

Verapamil and nifedipine inhibition of contractions induced by potassium and noradrenaline in human mesenteric arteries and veins.

Ring preparations of human mesenteric arteries and veins were contracted by noradrenaline (1.8 x 10(-5)M) or potassium (127mM). Isometric tension was recorded. In the arterial preparations, the maximum response to noradrenaline was 97 +/- 8% (mean +/- S.E.M.) of that to potassium. In the veins, the corresponding figure was 38 +/- 4%. The calcium antagonists verapamil (2.2 x 10(-7)-2.2 x 10(-5)M) and nifedipine (2.9 x 10(-8)-2.9 x 10(-6)M) relaxed both arteries and veins contracted by noradrenaline or potassium, and reduced the responses to these agents when added 15 min. before stimulation. The time course of relaxation of potassium contracted preparations, induced by verapamil and nifedipine, was more rapid and complete than that produced by a calcium-free, high potassium solution. In contrast to verapamil, nifedipine caused a more pronounced inhibition of the potassium than of the noradrenaline evoked contractions in both arteries and veins. After exposure to a calcium-free medium for 30 min., the arterial response to noradrenaline was significantly (P less than 0.05) greater than that to potassium. However, the reverse was found in the veins. In both types of vessel, verapamil (2.2 x 10(-6)M) and nifedipine (2.9--10(-7)M) were equi-effective in reducing the noradrenaline reactivity, not only between mesenteric arteries and veins, but also between, e.g. peripheral and mesenteric vessels. The calcium antagonists nifedipine and verapamil do not have an identical mode of action. However, both agents seem to inhibit influx of extracellular calcium, and might also have an inhibitory effect on the release of intracellular calcium.

Aged↗
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 in isolated human pulmonary vessels.

In isoalted human pulmonary arteries and veins the contractile response to noradrenaline (1.8 X 10(-5)M) was 33 +/- 7.4% and 20 +/- 4.5% (Mean +/- S.E.M.) of that induced by potassium (127 mM). A variable degree of spontaneous contractile activity was recorded in the vein preparations. This activity was abolished by nifedipine (2.9 X 10(-6)M). Digoxin (10(-6)M) induced contractions in pulmonary vessels. In the arteries, the digoxin contraction developed slowly and reached a maximum amplitude of 90 +/- 4% (Mean +/- S.E.M.) of the potassium evoked contraction. In the veins, the amplitude of the digoxin contraction was 32 +/- 5% of that induced by potassium. Digoxin (10(-6)M) also increased the maximum response to noradrenaline and potassium in both arteries and veins. In the arteries, the noradrenaline and potassium contractions increased to 211 +/- 6.8% and 145 +/- 8.9 of control, and in the veins to 169 +/- 13.5% and 163 +/- 9.9%, respectively. Nifedipine in concentrations which completely relaxes arterial and venous preparations contracted by potassium, had only a slight relaxing effect on digoxin induced contraction. It is concluded that digoxin increases the tension in pulmonary arteries and veins, and increases the maximum response to noradrenaline and potassium in both types of vessels. The digoxin induced contraction is highly resistant to blockade of extracellular calcium influx.

Adult↗
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

Pharmacokinetics of furosemide in anephric patients and in normal subjects.

The pharmacokinetics of furosemide 40 mg i.v. were compared in 7 anephric patients and in 7 normal subjects. The average serum clearance was 66 ml/min in the patients and 219 ml/min in the normal subjects, and the corresponding weight corrected clearances were 1.33 ml/min . kg and 2.96 ml/min . kg. Binding to serum proteins was significantly decreased in the anephric subjects, in whom a significant negative correlation was found between the percentage binding and the volume of distribution VDSS. In the patients, but not in the normal subjects, there was a significant positive correlation between VDSS and serum clearance. Both in normal and anephric individuals 4-chlor-5-sulphamoyl-anthranilic-acid (CSA) was found, but there was no evidence of special accumulation either of CSA or anthranilic acid in the anephric patients. In the patients the initial increase in serum concentration of sodium and protein followed by a more conspicuous decrease were more pronounced, but none of the changes were statistically significant.

Adolescent↗
PubMed1978

Effects of verapamil and nitroglycerin on contractile responses to potassium and noradrenaline in isolated human peripheral veins.

Isolated ring preparations of human vein were contracted by potassium (127 mM) and noradrenaline (1.8 X 10(-5) M). The potassium-induced contracture developed more rapidly and had a higher maximum amplitude than that produced by noradrenaline. Addition of phentolamine (10(-5) M) reduced the amplitude of the potassium contracture by 22% and abolished the noradrenaline response. Verapamil and nitroglycerin relaxed preparations contracted by potassium and noradrenaline, and, when added prior to stimulation, reduced the contractile responses to these agents. Both verapamil and nitroglycerin inhibited the contractile effect of noradrenaline more strongly than that of potassium. After immersion of the preparations for 30 min. in a calcium-free medium, the responses to potassium and noradrenaline were reduced to 21.3 +/- 2.5% and 7.1 +/- 0.8%, respectively, of the control. Addition of verapamil caused a further reduction of the response to potassium, but not of that to noradrenaline. Nitroglycerin caused a further reduction of the contractions induced by both agents. When the calcium concentration in the extracellular medium was increased from 0 to 4 mM, the contractile responses to potassium and noradrenaline returned to the control level. Both verapmil and nitroglycerin inhibited the contractile responses to calcium; the inhibiting effects of verapamil were significantly more marked than those of nitroglycerin. Tachyphylaxis to nitroglycerin was demonstrated on contractions induced by potassium, but not on noradrenaline-produced responses.

Adult↗