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Biomedical subjects

G Muiesan

Publications and source records attributed to G Muiesan.

At least 73 records · Page 4Linked to original sources

Efficacy of low-dose captopril given twice daily to patients with essential hypertension uncontrolled by a beta blocker plus thiazide diuretic.

Thirty-two patients with moderate to severe essential hypertension whose supine diastolic blood pressure (SDBP) was greater than or equal to 95 mm Hg following 2 weeks' treatment with the optimal dosage of beta blocker-diuretic combination were randomly assigned to the addition of either captopril 25 mg or 50 mg b.i.d. After 6 weeks' treatment, if patients were not normalized (SDBP less than 95 mm Hg), the dose of captopril was doubled for a further 6 weeks. The addition of captopril led to a significant fall in standing and supine diastolic and systolic blood pressure at the end of the sixth and twelfth week of treatment. There was no difference in the change in blood pressure between the two groups. At the end of the study SDBP was normalized in 66% of patients and a further 12.5% had their SDBP reduced by greater than 10%. Captopril 25 or 50 mg administered twice daily proved to be a very effective antihypertensive agent when added to a beta blocker-diuretic combination in patients resistant to optimal doses of these drugs.

Adult↗

Supine and standing plasma catecholamines in essential hypertensive patients with different renin levels.

In this study we measured plasma renin activity (PRA), plasma norepinephrine (NE) and epinephrine (E), heart rate (HR) and blood pressure (BP) in 89 supine (sup) essential hypertensive patients (pts), WHO I-II, after 3-5 days of fixed normal sodium and potassium intake; the same measurements were repeated after 30' of active standing (stand) in 44/89 pts. In the whole population NE was directly related to PRA, both in sup and in stand position (p less than 0.01). NE was above the upper limits of normotensive controls in 2/34 (6%) pts with low PRA, in 6/40 (17%) pts with normal PRA and in 6/15 (40%) pts with high PRA. In respect to normal PRA pts, HR was significantly lower in low PRA pts and higher in high PRA pts, both in sup and in stand position (p less than 0.05). Sup and stand NE and E were similar in low and normal PRA pts, while they were significantly higher in high PRA pts (p less than 0.05). These results suggest an increased adrenergic tone at least in some high PRA pts, and blunted responsiveness of renal and cardiac beta adrenergic receptors to adrenergic stimuli in low PRA pts.

Adult↗

[Continuous 24-hour registration of intra-arterial pressure in basal states and during therapy with a fixed slow-release oxprenolol-chlorthalidone combination, administered once a day].

Intra-arterial 24 hour blood pressure (BP) recording (OXFORD MEDILOG) was carried out in 10 patients with essential hypertension, 6 males and 4 females, aged between 41 and 58 years, 3 at WHO stage 1 and 7 at stage 2, in basal conditions and after 6 weeks of treatment with a fixed combination of 160 mg of slow-release oxprenolol and 20 mg of chlorthalidone per tablet (tb). The fixed combination was given once daily, in the morning, at the dosage of 1 tb, which was increased to 2 tbs o.d. after the first 2 weeks in 6 patients. Computer calculated mean BP and heart rate (HR) values from each consecutive hour of the day were obtained in all patients. Hourly trend of BP and HR were plotted and circadian variations were thus determined. Treatment with fixed combination o.d. significantly reduced systolic and diastolic BP, compared to pretreatment values, throughout of the 24 hours (p less than 0.01; p less than 0.001), without altering the circadian rhythm. Before and after 6 weeks of treatment, a bicycle exercise test was performed in 8 patients, who reached 85% of the maximal predicted HR. Pretreatment resting mean BP (+/- SD) was 190 +/- 31/108 +/- 10 mmHg (HR: 68 +/- 9 b/min) and those during the last minute of exercise 242 +/- 29/125 +/- 5 mmHg (HR: 147 +/- 13 b/min); posttreatment resting BP was 161 +/- 20/88 +/- 7 mmHg (HR: 58 +/- 7 b/min) and at peak exercise, 212 +/- 16/106 +/- 7 mmHg (p less than 0.025 for the systolic pressure; p less than 0.001 for the diastolic pressure).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Relationships between plasma catecholamines, renin, age and blood pressure in essential hypertension.

The aim of this study was to examine the interrelationships between age, plasma catecholamines, plasma renin activity (PRA) and blood pressure in essential hypertensive (EH) patients. PRA, plasma noradrenaline (NA) and adrenaline (A) were measured in 76 consecutive EH patients (WHO stages 1-2, aged 24-66 years) and in 28 normotensive subjects (aged 25-64 years) studied at rest in supine position after 5 days of normal fixed sodium and potassium intake. Both plasma NA and A were slightly but significantly higher in EH patients (p less than 0.05). While no relationship was found between the various parameters in normotensive subjects, in EH patients, particularly those at WHO stage 2, plasma NA was directly related to mean blood pressure (MBP) (p less than 0.001) and PRA (p less than 0.01). Plasma A was weakly related to MBP (p less than 0.05); PRA was inversely related to age (p less than 0.01) but no relationship was found between NA or A and age. Partial correlation analysis confirmed all these relationships. In fact, NA was related to MBP also considering constant PRA (p less than 0.001) or age (p less than 0.001), and NA was related to PRA also considering constant MBP (p less than 0.01) or age (p less than 0.001). Acute pharmacological alpha- and beta-blockade, with labetalol 100 mg i.v., induced a reduction of MBP which was directly related to basal plasma NA (p less than 0.001). These results support the view that in EH the sympathetic nervous system might be in part responsible for PRA levels and for the severity of hypertension.

Adult↗

Dissociation of effects of hypertrophy from hypertension on cardiac beta-receptors in renovascular hypertensive rats.

Reduction in density of beta-adrenoceptors has been demonstrated in the hypertrophied left ventricle (LV) of renovascular hypertensive rats (RHR). In order to investigate the relative role of cardiac hypertrophy as distinct from hypertension, LV beta-receptors were determined in RHR four days after nephrectomy of the clipped kidney (RHR-Nx) when blood pressure was reduced but hypertrophy still evident; the results were compared with those obtained in age-matched untreated RHR and sham operated rats (SHAM). As expected, blood pressure (BP) was reduced four days after nephrectomy (150 +/- 3 versus 212 +/- 11 mmHg untreated RHR, P less than 0.001) but LV hypertrophy had not regressed (3.07 +/- 0.16 versus 3.58 +/- 0.24 mg/g, NS). Ventricular beta-receptor density was reduced in both RHR (1.601 +/- 0.078 pmol/g) and RHR-Nx (1.667 +/- 0.124 pmol/g) compared with SHAM (2.033 +/- 0.06 pmol/g, P less than 0.05 for both). The dissociation constant (Kd) was not different among the three groups. Thus, the reduction of beta-adrenergic receptors in the hypertrophied LV of RHR persisted even when BP was lowered by nephrectomy, suggesting that hypertrophy per se rather than hypertension accounted for that reduction in cardiac beta-receptors.

Animals↗

Angiotensin-converting enzyme inhibition, catecholamines and hemodynamics in essential hypertension.

Captopril was given to 15 unselected patients with essential hypertension (WHO II) at a dose range of 300 to 600 mg/day. Hemodynamic indexes (thermodilution) as well as levels of plasma norepinephrine, epinephrine, renin activity and aldosterone were determined simultaneously at the end of 2 weeks of placebo and after 8 weeks of captopril treatment. Systolic and diastolic arterial pressures were reduced significantly by treatment both supine (p less than 0.0025) and standing (p less than 0.0025). The diastolic arterial pressure was normalized (less than 95 mm Hg) in five patients and significantly reduced in four, whereas six patients were considered poor responders (mean arterial pressure decrease 10 mm Hg or less). The decrease in arterial pressure correlated significantly with the reduction in total peripheral resistance (r = 0.71), whereas cardiac index did not change and stroke index increased because of a slight decrease of heart rate. Plasma and urinary norepinephrine and epinephrine did not change during treatment. Moreover, the response of both heart rate and plasma catecholamines to upright posture was not altered by captopril treatment. Plasma renin activity increased and plasma aldosterone concentration decreased during treatment. These results suggest that inhibition of converting enzyme activity by captopril induces a reduction in arterial pressure through a reduction in total peripheral resistance. There was no evidence of an appreciable reduction in sympathetic nervous system activity during therapy.

Adult↗

Antihypertensive activity of once daily metoprolol alone and with chlorthalidone and comparison with a twice daily regimen.

In a multicentre, double-blind (DB), within-patient study, the antihypertensive effectiveness and tolerability of two oral administration schedules of metoprolol (M) 100 mg b.i.d. versus 200 mg once daily (o.d.), were investigated in 103 outpatients with mild to moderate essential hypertension. The study lasted 14 weeks and was divided into 3 periods: a) a weeks of single-blind (SB) placebo wash-out; b) 4 weeks of SB administration of M 100 mg b.i.d.; at the end of the second week of this period, chlorthalidone (C) 25 mg was added in patients with a recumbent diastolic blood pressure (BP) still greater than 95 mmHg and was continued throughout the following period; and c) DB cross-over administration of M 200 mg/d for 4 weeks on a b.i.d. schedule and 4 weeks on a once daily schedule. In comparison with pretreatment values, heart rate and systolic and diastolic BP were reduced (p less than 0.001) by both M administration schedules; there was no differences between the once and twice daily treatment regimens. During M once daily, betablockade was still maintained over 24 hours or longer, as the heart rate remained significantly lower than the basal value. In 57 patients, C was added at the end of the second week of SB M administration, and a further decrease in BP was observed; again, there was no significant change during once and twice daily M administration. Unwanted effects during M treatment were of minor severity, and the majority occurred when C, too, was added.

Administration, Oral↗

The acute and chronic hypotensive effect of labetalol and the relationship with pretreatment plasma noradrenaline levels.

1 Labetalol 100 mg was given intravenously to 27 patients with essential hypertension (12 males, 15 females; WHO I-II; age range 30-66 yr; on average, a significant reduction of blood pressure was observed within 5 min (P less than 0.001). Average heart rate was also reduced significantly (P less than 0.01). 2 In 18 patients haemodynamic measurements were performed (dye-dilution or thermodilution technique): blood pressure reduction was related to peripheral vasodilatation, as cardiac index remained unmodified. 3 The absolute and percentage decrease of blood pressure, heart rate and total peripheral resistance after labetalol 100 mg intravenously, was significantly greater in the patients with higher baseline plasma noradrenaline concentration values. 4 In 12 out of 27 patients labetalol was given orally for 2 months (dose range 300-1200 mg); the pattern of blood pressure and heart rate changes after oral therapy were comparable to those observed after acute administration of the drug. 5 The degree of blood pressure and heart rate reductions after oral labetalol was also significantly related to pretreatment basal noradrenaline concentration.

Administration, Oral↗

Aortic rigidity and plasma catecholamines in essential hypertensive patients.

Aortic rigidity, plasma noradrenaline and adrenaline, and hemodynamic parameters were measured in 48 essential hypertensive patients, 25 younger than 45 (Group I) and 23 of 45 years and over (Group II). Aortic rigidity was determined by the ratio of pulse pressure over stroke volume. Aortic rigidity and hemodynamic parameters were also determined after combined alpha-beta receptor blockade induced by Labetalol (mg 100 IV) or by Propranolol (mg 10 IV) plus Phentolamine (mg 10 IV). The aortic rigidity index was significantly higher in Group II, systolic arterial pressure being significantly higher. All other data, including plasma noradrenaline and adrenaline, were not significantly different in the two groups. In Group II a significant correlation (r = 0.62) was noted between aortic rigidity indexes and plasma noradrenaline values. The alpha-beta receptor blockade induced a decrease of aortic rigidity particularly in Group II, owing to a more marked decrease of systolic arterial pressure. A highly significant correlation was noted in Group II between the changes in aortic rigidity index and the basal plasma noradrenaline levels (r = 0.81). Therefore, the aortic rigidity in essential hypertensive patients older than 45 is influenced by the sympathetic nervous system activity, as judged by plasma noradrenaline levels. This influence seems related to an increase with age of aortic responsiveness to sympathetic stimulation.

Adult↗

Adrenergic activity in systolic hypertension.

Basal hemodynamics and plasma catecholamines were measured in 10 patients with systolic hypertension, 7 males and 3 females, aged 38-69 years (Group 1), and in 10 patients with systolic and diastolic hypertension, 7 males and 3 females, aged 40-65 years (Group 2); the same measurements were repeated after acute pharmacological alpha and beta-blockade with Labetalol, 100 mg iv, or Propranolol, 10 mg iv, plus Phentolamine, 10 mg iv. In patients of Group 1 plasma noradrenaline was inversely related to systolic arterial pressure and to stroke index and was directly related to heart rate. In patients of Group 2 plasma noradrenaline was directly related to systolic arterial pressure. After acute alpha and beta-blockade the degree of reduction of systolic arterial pressure was directly related to basal plasma noradrenaline in both groups; systolic arterial pressure was reduced to normotensive levels in 5 patients of Group 1 who had high basal plasma noradrenaline values. These results confirm some of our previous findings and suggest that in some patients with systolic hypertension adrenergic activity is increased and may have a significant role in maintaining high blood pressure values.

Aged↗

Antihypertensive and humoral effects of verapamil and nifedipine in essential hypertension.

The aim of this study was to investigate and compare the effects of two calcium antagonist drugs, verapamil (VER) and nifedipine (NIF), on blood pressure (BP), heart rate (HR), plasma catecholamines (pCA), renin (PRA), plasma aldosterone (pALD), and plasma volume (PV) in a group of patients with mild to moderate essential hypertension. In 12 hypertensive patients on a fixed normal sodium and potassium intake, VER (80 mg t.i.d., per os) first and then NIF (10 mg, t.i.d. per os), or vice versa according to a random sequence, were each given for 8 days, with an interval of 5 days between the two treatments. Both NIF and VER significantly reduced BP (p less than 0.001); this reduction was quantitatively similar in both treatment schedules. Supine and standing PRA, pALD, and PV were not significantly affected by VER or NIF. HR and pCA were unchanged after VER, whereas they were significantly increased (p less than 0.05, at least) mainly in standing position after NIF treatment. The antihypertensive and metabolic effects of VER (80 mg t.i.d.) and NIF (10 mg t.i.d.) were maintained after chronic treatment (4 months with VER in 10 patients and 2 months with NIF in 12 patients). After 2 months of treatment with VER (160 mg t.i.d.) in 18 patients, BP was further reduced, while pCA were slightly increased. In conclusion, VER and NIF are effective and equipotent antihypertensive agents that do not induce significant renin stimulation or fluid retention; adrenergic stimulation seems to be greater with NIF, which should be taken into account in the clinical use of these drugs.

Adult↗

Effects of prizidilol (SKF 92657) on blood pressure, haemodynamics, sympathetic nervous system activity and plasma volume in essential hypertension.

1. The antihypertensive effect of 4 weeks' treatment with prizidilol (SKF 92657) (mean dosage 520 mg once or twice daily) was studied in ten essential hypertensive patients. 2. Both systolic and diastolic blood pressure were significantly reduced in all cases. Supine heart rate did not change, and in the erect position heart rate was significantly lowered. 3. Blood pressure reduction was due to peripheral vasodilatation, as the cardiac index increased after 4 weeks of prizidilol treatment. 4. After prizidilol plasma noradrenaline and adrenaline increased significantly, and PRA and plasma aldosterone were reduced. Although plasma volume increased, body weight did not change. 5. Cardiac performance, as evaluated by the PEP/LVET ratio, improved after treatment with prizidilol.

Adult↗

A fixed combination of oxprenolol slow-release and chlorthalidone once daily in treatment of mild to moderate hypertension.

In a multicenter, single-blind, interpatient study, 103 outpatients with mild to moderate hypertension were given, after 2 weeks of placebo wash-out, 160 mg oxprenolol slow-release in fixed combination with chlorthalidone (20 mg per tablet) (SROC 160) once daily or conventional oxprenolol (80 mg) in fixed combination with chlorthalidone (10 mg per tablet) (COC 80) twice daily for 8 weeks. Throughout the study 22 of 51 patients on SROC 160 and 24 of 51 on COC 80 received 1 tablet once daily and, respectively, 1 tablet twice daily. The remaining patients of both groups double the corresponding dosage after the first 4 weeks. Systolic and diastolic blood pressure decreased on both treatments without and difference observed between the groups. Diastolic blood pressure normalization was achieved in both groups in the same number of patients (35). Minor side effects occurred on both treatments: only one patient on SROC 160 interrupted the study due to severe dizziness and fatigue. The advantages are discussed as regards patient's compliance with administration of fixed combination SROC 160 once daily in treatment of mild to moderate hypertension.

Adult↗