Biomedical subjects
Publications and source records attributed to O Andersson.
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The serotonin (S2) antagonist, ketanserin was given to 16 patients with essential hypertension on a single-blind basis. Ten patients were treated for 3 years with ketanserin 40-80 mg daily on a once or twice daily regimen. In this group supine blood pressure fell from 164 +/- 4/101 +/- 2 mmHg on placebo to 152 +/- 5/91 +/- 3 mmHg (NS/P less than 0.01) after 3 years of therapy. During treatment, total serum cholesterol remained essentially unchanged while serum triglycerides were significantly reduced. No side-effects were seen except for dry mouth or slight nasal congestion reported by two patients. In six patients regional haemodynamics were assessed by forearm plethysmography. After 3 months of ketanserin, resting vascular resistance was significantly reduced from 58.3 +/- 12 units on single-blind placebo to 47.0 +/- 12 units (P less than 0.005) on single-blind ketanserin, 40 mg twice daily. We conclude that ketanserin is an effective antihypertensive agent during long-term therapy with some beneficial effects on serum lipids. The antihypertensive effect seems to be mediated chiefly by a decrease in vascular resistance.
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Central and peripheral haemodynamics were studied noninvasively (echocardiography, plethysmography) in normotensive young men (mean age 30 years) with (n = 17) (H), and without (n = 15) (C) a positive history of hypertension during normal salt intake and after four weeks of ordinary diet plus 12 g NaCl daily. No changes in blood pressure were noted during the course of the study in either group. After three days of high salt an increased cardiac output and decreased total peripheral resistance was seen in H but not in C. The former might be due to a salt induced volume load occurring in a less distensible venous system. The difference in response disappeared during the course of the study. Both on normal and high salt intake resting resistance and resting vascular tone were significantly higher in H reflecting an increased contractile state of the smooth muscles of the resistance vessels. The increased smooth muscle tone of the resistance vessels and the less distensible venous system in these young men with family history of hypertension might be a genetically determined basis for a future increase in blood pressure.
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Ten slightly obese middle-aged men were instructed to increase their energy intake 25% during a period of 1 week, which was preceded by a control period of seven days. Body weight increased by 0.67 kg (SD 0.60) indicating good compliance with the regimen. Transmembrane sodium fluxes were determined with the use of 22Na. The pre-diet erythrocyte sodium content was 9.7 mmol/L (SD 0.8) decreasing to 8.9 mmol/L (SD 1.1) (P less than 0.05) during overfeeding. The Na-efflux rate constant increased from 0.40 h-1 to 0.54 h-1 (P less than 0.05). Urinary excretion of catecholamines and concentrations of catecholamines and insulin in plasma and of thyroxine, triiodothyronine, and reverse T3 in serum did not change. Thus, overfeeding seems to enhance the total Na efflux in erythrocytes from slightly obese men. There were no measurable changes in thyroid hormone or catecholamine levels leaving the regulatory mechanisms unexplained.
During 4 weeks 37 normotensive 50-year-old men identified by screening in a random population sample were given 12 g of NaCl daily, in addition to their usual dietary sodium intake. Blood pressure, heart rate, weight, urinary excretion of sodium, potassium and catecholamines, plasma aldosterone and noradrenaline and intra-erythrocyte sodium content were determined on normal and increased salt intake. The subjects were divided into those with a positive family history of hypertension (n = 11) and those without such a history (n = 26). Systolic blood pressure and weight increased significantly irrespective of a positive family history of hypertension. On normal salt intake intra-erythrocyte sodium content was significantly higher in those with a positive family history of hypertension. During high salt intake intra-erythrocyte sodium content decreased significantly in that group and the difference between the hereditary subgroups was no longer significant. In the whole group urinary excretion of noradrenaline, adrenaline and dopamine increased whereas plasma aldosterone decreased during the increased salt intake. Thus, in contrast to some earlier studies performed in young subjects, our results indicate that moderately increased sodium intake acts as a pressor agent in normotensive middle-aged men whether there was a positive family history of hypertension or not. We confirm that men with positive family history of hypertension have an increased intra-erythrocyte sodium content, and that an increase in salt intake seems to increase overall sympathetic activity.
Seventeen young normotensive men with a family history of hypertension in two generations (H) and 15 age-matched control subjects (C) were studied with respect to blood pressure (BP), intraerythrocyte sodium content (IeNa), sodium influx, and rate of sodium efflux. The investigations were done during normal salt intake and after 4 weeks of ordinary intake plus 12 g NaCl daily. BP did not increase significantly in either of the two groups during increased salt intake. During normal salt intake H had a significantly (p less than 0.01) higher IeNa (9.5 +/- 1.5 mmol/L) compared with C (8.2 +/- 1.4 mmol/L). During high salt intake IeNa in H decreased significantly to 8.1 +/- 1.2 mmol/L, the difference from C (7.6 +/- 1.2 mmol/L) not being significant. While the Na influx was similar in the two groups, the rate constant for Na efflux was significantly lower during normal salt intake in H (0.23 +/- 0.08 vs 0.29 +/- 0.1 h-1, p less than 0.05). Salt intake increased the efflux rate constant significantly in H (0.28 +/- 0.08 h-1, p less than 0.05), while it did not change significantly in C (0.32 +/- 0.08 h-1) compared with the value for normal salt intake. Our results suggest that young men with a hereditary predisposition to hypertension have a higher IeNa secondary to a lower rate of Na efflux, while a normal Na influx indicates normal cell permeability to Na. The findings in H during high Na intake--a decreased IeNa and an increased efflux rate of Na--do not favor the existence of a sodium transport inhibitor, in subjects predisposed to hypertension, increasing during high salt intake and volume expansion and acting through inhibition of the Na efflux.
Felodipine, a dihydropyridine, is a new vasodilating calcium antagonist which lowers blood pressure (BP) by selective action on vascular smooth muscle, especially in the resistance vessels. The effects on BP, heart rate (HR) and tolerance of different single oral doses of felodipine were studied in two series of hypertensive patients. When felodipine was given as single drug to 14 previously untreated hypertensives in a single-blind manner, BP was rapidly reduced by about 15% while HR increased by 25%. Felodipine given in a double-blind manner to eight patients on chronic beta-adrenoceptor blockade reduced BP by some 15-20% compared to placebo, while HR did not change. There was a significant correlation between the pre-treatment mean arterial BP (MAP) and the maximal relative change in MAP, i.e. the higher the initial BP the greater the reduction after felodipine. A significant correlation was also found between the plasma concentration of felodipine and the relative change in MAP. Felodipine was generally well tolerated. When given alone felodipine caused the side effects expected from a pure vasodilator, i.e. headache, flushing and palpitations. When given together with a beta-adrenoceptor blocker, the side effects were much less apparent.
The objective of this placebo controlled double-blind multicentre (six centres) trial was to investigate the safety and efficacy of ICI 141,292 (Visacor), a new selective beta 1-adrenoceptor antagonist with modest intrinsic sympathomimetic activity (ISA), in hypertensive patients. Fifty-nine patients with mild essential hypertension were randomized to two of five treatment alternatives (placebo, 50 mg, 100 mg 200 mg or 300 mg of ICI 141,292) each given once daily for 2 weeks with a 4 week placebo period before (run in) and in between (wash out) active periods. Thus, each of the five treatments was evaluated in 20-24 patients. After 2 weeks (24 h after last dose) the reduction in recumbent blood pressure for all doses except 50 mg of ICI 141,292 was statistically significant and in the order of 6/4 mm Hg. Standing systolic blood pressure was reduced in a dose-dependent way but only significant for 200 mg of ICI 141,292 (8 mm Hg). Heart rate changes (delta) less than 4 beats/min) were not statistically significant for any dose. It is concluded that ICI 141,292 was well tolerated and had a significant but weak antihypertensive effect which might be explained by too much beta 1-adrenoceptor ISA.
A review is made to sum up the indications when diuretics may be the drug of choice in the treatment of hypertension. Advantages from the combined treatment of thiazide diuretics and other antihypertensive agents are also emphasized. Adverse effects from diuretic treatment, i.e. hypokalemia, hyperuricemia, impaired glucose tolerance and risks associated with unfavourable serum lipoprotein patterns are discussed. It is concluded that from a hemodynamic point of view thiazide diuretics can be a good therapeutic alternative for most patients, excepting those with hyperkinetic circulation. It is recommended to use lower doses of thiazide diuretics than previously and the monitoring of S-potassium is necessary in all patients.
Two groups of obese, normotensive men were put on weight-reducing diets in an outpatient study. The groups were comparable with regard to age, weight, heart rate, blood pressure, energy and salt intake during a four-week control period. In a four-week dieting period, Gp I (n = 12) received an energy-reduced diet (1370 kcal, 5.7 MJ) with 24 energy per cent carbohydrates. Group II (n = 11) had an isocaloric diet (1400 kcal, 5.8 MJ) with 59 energy per cent carbohydrates consisting of mainly mono- and disaccharides. Significant decreases in systolic blood pressure, heart rate, plasma noradrenaline and urinary excretion of noradrenaline were observed in Gp I but not in Gp II. Weight reduction and decrease of urinary sodium output was equal in both groups. No difference in alcohol consumption was recorded. We conclude that in obese normotensive patients a high proportion of mono- and disaccharides counteracts the expected hypotensive response of weight reduction. On the other hand, and judged from the present data, the blood pressure decrease observed in the group on a low carbohydrate diet seems to be secondary to an effect on the sympathetic nervous system.
Fourteen men with moderately severe essential hypertension were treated with prizidilol hydrochloride 400-700 mg once daily (mean +/- S.D. 612 +/- 56 mg/day). The study was open and ambulatory, with an initial placebo period followed by dose titration of prizidilol. Prior to treatment and during optimal control of blood pressure cardiovascular adaptation was examined in a submaximal exercise test. Plethysomographic assessment of vascular flow, resistance and tone in the calf musculature during supine rest and during maximal vasodilatation was also performed. A highly significant reduction in systolic (from 164 +/- 4.5 to 141 +/- 2.7 mmHg; p less than 0.001) and diastolic blood pressure (from 105 +/- 1.6 to 87 +/- 1.3 mmHg; p less than 0.001) at supine rest was noted during therapy with prizidilol. There was no significant change in heart rate. Systolic pressure in the standing position was reduced (from 159 +/- 4.2 to 139 +/- 2.9 mmHg; p less than 0.001) and so was the diastolic pressure (from 111 +/- 2.5 to 95 +/- 1.9 mmHg; p less than 0.001). The heart rate in the standing position was significantly increased compared to supine rest in the placebo period and during optimal treatment with prizidilol. The beta-adrenoceptor blocking properties of prizidilol were apparent as a reduction in the exercise-induced heart rate response at even the lowest work load. During prizidilol therapy an increase in resting calf muscle blood flow was found from 3.1 +/- 1.5 ml/min X 100 ml to 4.3 +/- 2.1 ml/min X 100 ml (p less than 0.025). Vascular resistance and vascular tone were significantly reduced.(ABSTRACT TRUNCATED AT 250 WORDS)
Series of female virgin and pregnant albino mice were i.v. injected with 14C-labelled- or unlabelled toxaphene (16 mg/kg b.w.). After survival times ranging from 1 min to 32 days the toxaphene distribution in the body was studied using whole-body autoradiography and capillary gas-chromatography. Autoradiographic studies have shown that after an initial accumulation in the liver, brown fat, lung, brain, kidney, and ovaria (corpora lutea) there was a gradual redistribution of radioactivity to the white fat within 4 h postinjection. The labelling was then decreasing rapidly and only negligible amounts of the radioactivity were present in the adipose tissue after 32 days. In the fetus only the liver and adrenals showed a distinct labelling. A specific and persistent accumulation of the label was detected in some zones of the adrenal cortex suggesting a possible direct interference of toxaphene with adrenal steroid hormone synthesis. The gas chromatographic pattern of toxaphene-derived residues in the tissue samples resembled that of the technical toxaphene, but was changing in different tissues with the time. The liver chromatograms indicated more extensive formation of metabolites.
Acute low spinal and curarized cats injected with noradrenergic agonists i.v. can elicit an efferent burst pattern which can be recorded in muscle nerve filaments and can be referred to as "fictive locomotion". This study investigates the effect that feedback, arising from movements in the hip joint, can exert on the central network generating fictive locomotion. The central network is uncoupled from generating any active movements by curarization. The motor pattern could be entrained by applying sinusoidal hip movements, even when a very extensive denervation of the leg had been performed leaving only some of the muscles around the hip and the hip joint innervated. During flexion movements, efferents to different flexor muscles became active and during movements in the reverse direction (extension), efferents to extensors were active. With an increasing movement frequency the onsets of both flexor and extensor bursts were delayed in the movement cycle. The duration of the extensor bursts varied markedly with the movement cycle, whereas pure flexors changed less in burst duration. The frequency within which the efferent burst activity was entrained in a strict 1:1 relation to the movement varied between 5 to 70% above and below the resting burst period. In preparations with a narrow 1:1 range, a "relative coordination" was encountered outside this range. The flexor burst duration was in these cases dependent on where in the hip movement cycle the bursts appeared.
Blood pressure (BP), sodium in erythrocytes (IeNa) and transmembrane sodium fluxes were determined in normotensive 30 and 50-year-old men with a family history of hypertension (group H; n = 17 and 11 respectively) and without such history (group C; n = 15 and 26 respectively) during normal salt intake and after four weeks on ordinary diet plus 12 g NaCl daily. The 50-year-old men showed a significant increase in BP and weight during high salt intake while the younger men did not. On normal salt, group H had a significantly higher IeNa than group C in both age groups. In the younger group this was accompanied by a decreased Na efflux rate constant. IeNa decreased significantly in group H in both age groups. The decrease in IeNa and increase in pump activity in group H during high salt intake does not support the existence of a sodium transport inhibitor. The increase in BP in the older group during high salt indicates that age is an important factor in BP response.
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The antihypertensive effect and metabolic side effects of bendroflumethiazide have been compared with those of propranolol in two randomly selected groups, of 53 previously untreated middle-aged men during 6 years' treatment for mild to moderately severe essential hypertension. The blood pressure-reduction was the same in the two groups. During the follow-up 1 man in the bendroflumethiazide group and 3 in the propranolol group died while 2, 1 on each treatment, became diabetic. None had gout but serum urate increased in both groups. Glucose tolerance improved significantly in both groups during the first year and this improvement was sustained for the follow-up period. Serum potassium did not differ in the two groups during the first 5 years but during the sixth year it decreased in the diuretic group. Total potassium was, however, unchanged in both groups. These results indicate that the frequency of metabolic side effects during diuretic treatment of mild to moderately severe essential hypertension is low and has been grossly exaggerated. Since the antihypertensive effect and side effects were equal with both drugs, and since the diuretics are cheaper, they should be the drug of first choice in this type of hypertension.