[Vasodilating agents in the treatment of hypertension - a review].
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Biomedical subjects
Publications and source records attributed to O Andersson.
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28 patients, aged 35-62 years, with uncomplicated hypertension, entered a double-blind, crossover study, in which the effects of single daily doses of sotalol and metoprolol were compared. Both drugs exerted a clinically useful anti-hypertensive effect as monotherapy, or in combination with a thiazide diuretic. No significant difference in hypotensive effects was noted between the two beta-blocking agents, when the dose was titrated to an optimal clinical effect. Treatment with sotalol and metoprolol was associated with a clinically insignificant increase in serum uric acid concentration. The side-effects observed were few, and in only two cases was therapy discontinued. We regard both sotalol and metoprolol as useful anti-hypertensive drugs.
Acute spinal and curarized cats can generate "fictive locomotor activity" after an i.v. injection of Nialamid followed by 4-AP and L-DOPA. The efferent burst activity to flexors and extensors can be recorded in peripheral nerve filaments. Ramp-formed movements were applied in the hip at constant angular velocity in different phases of the spontaneous efferent burst activity. The cycle duration was markedly influenced. A flexion or an extension ramp applied in the early part of the "step-cycle" (during flexor activity) will prolong the cycle duration, but in the later part of the cycle instead a marked shortening effect will occur. The transition from a prolongation to a shortening is very steep for the extensive-ramps, with a subsequent gradual increase from a shortening to a lengthening of the cycle. This type of phase response curve expresses a potent peripheral modulatory effect on the central pattern generator. A ramp movement (flexion or extension) applied in the beginning of the flexor burst will reinforce the flexor activity. In the end of the flexor burst instead there is a directional sensitivity with positive feedback, resulting in an excitation of the flexor activity for flexion ramps, but a depression of the flexor activity for extension-ramps. Extension-ramps also show a position dependent effect which enhances the response in the flexors for more extended hip positions.
The feedback mechanisms taking part in the control of locomotion in cat and fish are reviewed, particularly with regard to position- and movement-related feedback. It is shown that in both fish and cat there is a powerful position-dependent negative feedback which will act only in the position range where the muscle activity normally changes, e.g., from extensor to flexor activity. In addition, there is positive feedback in the middle of the movement range which will act in certain conditions, e.g., to promote and maintain flexor activity during the flexion of the hind limb.
Body composition, glucose metabolism and indices of sympathetic nervous activity were studied in two different samples of unselected normotensive and hypertensive middle-aged men. The hypertensive subjects were more often obese and had more often an impaired glucose tolerance and a higher fasting insulin compared with the normotensives. The metabolic differences were not explained simply by the higher degree of obesity in the hypertensives, but seemed also to be related to an increased excretion of noradrenaline, ie to an increased overall sympathetic activity. The impaired glucose metabolism might be one of the factors explaining the variable prognosis in essential hypertension.
In 41 apparently healthy men, aged 22-25 years, with mild blood pressure elevation (MBPE) and 19 age- and sex-matched normotensive controls (MC), blood pressure (BP) and heart rate (HR) readings at the clinic were compared to self-determined morning and afternoon values at home. The criteria for inclusion in the MBPE group were auscultatory BP less than 150 mmHg systolic and/or less than 90 mmHg diastolic at the military enlistment center from which the subjects were recruited, and systolic BP less than 140 mmHg on two subsequent occasions at the clinic. The BPs of the controls, who were mainly recruited from the same center, did not exceed 130/80 mmHg either at the enlistment center or at the clinic. The magnitude of the difference in systolic BP between home and clinic readings in the MBPE group (+15.3 mmHg) differed significantly from that in the NC group (+1.8 mmHg) (p less than 0.001). In both groups the systolic BP increased slightly but significantly during the day and was higher at home in the afternoon than in the morning. HR showed the same type of variation as BP in both groups with higher values at the clinic. The rise tended to be more pronounced (p less than 0.1) in patients with MBPE. Surprisingly, resting HR at home in the morning was significantly lower in the MBPE than in the NC group. Normokinetic and hyperkinetic subgroups of patients with MBPE did not differ from each other with respect to the variations in HR and BP studied.
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1 A treatment group comprising 635 hypertensive men (casual SBP greater than 175 or DBP greater than 115 twice) was compared with a reference group (n = 391 men; casual SBP greater than 175 or DBP greater than 115 only at screening). All men belonged to the same population sample of 7,455 men aged 47-54 yr. 2 The two groups did not differ with respect to age, smoking habits or cholesterol values, but screening BPs were higher in the treatment group. 3 During 4.3 years' follow-up there was a significantly lower total death rate in the treatment group compared with reference group. 4 There was also a strong tendency towards lower incidence of non-fatal myocardial infarction (P = 0.06). The pooled incidence of non-fatal myocardial infarction and fatal CHD was lower in the treatment group than in the reference group (P less than 0.03).
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Tienilic acid has blood pressure lowering properties alone and in combined treatment with beta-adrenergic blocking agents; 250 mg of tienilic acid seems to correspond to 50 mg of hydrochlorothiazide. Tienilic acid effectively reduces serum urate and has no marked or rapid effect on potassium balance. During short-term treatment, no impairment of glucose tolerance was found.
Systemic BP reduction, calf blood flow and vascular resistance in the calf were determined in forty-two previously untreated patients with mild to moderate essential hypertension (WHO I-WHO II) before and after 6 weeks, 6 months and 18 months of BP-lowering treatment with mefruside (25 mg daily) or atenolol (100--400 mg daily). Blood flow was determined with venous occlusion plethysmography using a mercury-in-rubber strain gauge technique in the supine patient. Auscultatory BP was measured on the right arm simultaneously with the flow determinations and resistance was calculated from the flow and pressure. BP was reduced significantly and to the same extent by the two drugs. In the atenolol group a rise in resting resistance and a corresponding fall in resting blood flow was seen initially. These changes were entirely normalized during continued treatment for 18 months. In the mefruside group no significant haemodynamic changes during treatment were observed at rest apart from the BP fall. None of the drugs reduced resistance at "maximal" vasodilatation, indicating that no regress of the hypertensive structural changes of the calf blood vessels had taken place.
Severity of hypertension, frequency of secondary hypertension and prognosis have been compared in two groups of hypertensive men. The first group (n=686) was taken from a blood pressure screening of a total population sample. The other group (n=154) consisted of hypertensive men, referred to a hypertension clinic by physicians. The mean age of the groups was the same, (X=52 years, range 46--59 years). All went through the same investigations and were followed up and treated in a similar way at the hypertension clinic. The referred men had more severe hypertension, as shown by significantly more heart and kidney involvements. They also had a higher incidence of myocardial infarction, implying a poorer prognosis with regard to cardiovascular disease. The analysis shows the importance of a detailed description of studied groups, not only in terms of blood pressure, age and sex, but also with respect to the frequency and degree of present and previous signs of heart and kidney involvement. With such a description it is possible to compare results from different studies regarding pathophysiological mechanisms and the effect of treatment in hypertension.
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Within a group of 1026 men aged 47-54, cause-specific death-rates and the incidence of non-fatal myocardial infarction and stroke in treatment group of 635 hypertensive men (casual systolic B.P. greater than 175 or diastolic B.P. greater than 115 mm Hg on two occasions) treated at a hypertension clinic were compared with those in a control group of 391 men (causal systolic B.P. greater than 175 or diastolic greater than 115 mm Hg on only one occasion) who remained mainly untreated during their 4.3 years of follow-up. The predicted risk of coronary heart-disease (C.H.D.) at entry, calculated by a multiple logistic function, was slightly higher in the treatment group. Total death-rate during follow-up was significantly lower in the treatment group (3.3%) than in the control group (6.1%). The difference in death-rate for C.H.D. was of the same relative order (0.8% versus 1.5%), as was the incidence of non-fatal myocardial infarction (2.8% versus 5.4%), although none of the differences reached statistical significance. However, the pooled incidence of fatal and non-fatal C.H.D. was significantly lower in the treatment group (3.6%) than in the control group (6.9%). The results suggest that antihypertensive treatment might be effective in preventing or postponing C.H.D. in middle-aged men.