Long-term haemodynamic effects of amlodipine at rest and during exercise in essential hypertension.

Haemodynamic responses at rest and during exercise were studied in 18 patients with essential hypertension following long-term treatment with amlodipine. Patients underwent a 2-week placebo run-in period followed by a mean duration of 11 months' treatment with amlodipine 5-10 mg (mean dose 9 mg) once daily. Blood pressure was measured intra-arterially, cardiac output by dye dilution and heart rate by electrocardiogram. Amlodipine produced a mean reduction in systolic and diastolic arterial pressure of 27 and 16 mm Hg, respectively, at rest and after exercise. At rest sitting, mean systolic and diastolic arterial pressures were reduced by 16 and 14% (p less than 0.01), respectively, from initial mean values of 182.4/111.2 mm Hg. This reduction in blood pressure was associated with a marked reduction in the total peripheral resistance index of 19% (p less than 0.001). Similar responses were observed at rest supine and during exercise. No significant changes were seen in heart rate. Stroke index showed a small increase at rest and during exercise together with a trend towards an increase in cardiac index after treatment with amlodipine. Ambulatory blood pressure monitoring was carried out in 10 patients after the placebo run-in and at the end of the study. Amlodipine showed effective blood pressure control throughout the 24 h after one daily dose. The incidence of side effects was low (ankle oedema in 2 patients).

Long-term haemodynamic effects of amlodipine at rest and during exercise in essential hypertension.

Amlodipine administered once daily (5-10 mg) lowered blood pressure and reduced total peripheral resistance in patients with mild-to-severe essential hypertension without any reflex tachycardia. Heart pump function was maintained at rest and during exercise with a trend towards an increase in cardiac and stroke index. Amlodipine was effective and well tolerated in both young and elderly hypertensive patients with no reports of unpleasant vasodilator-related side effects.

Long-term haemodynamic effects of amlodipine at rest and during exercise in essential hypertension.

The long-term haemodynamic responses to amlodipine, a new long-acting calcium antagonist, were studied both at rest and during exercise in 18 patients (mean age 43 years) with essential hypertension. Blood pressure was measured intra-arterially, cardiac output by dye dilution and heart rate by electrocardiogram. After 11 months of treatment with 5-10 mg amlodipine once daily (mean dose 9 mg/day), mean arterial pressure was reduced by 14% sitting at rest. The reduction in blood pressure was associated with a marked reduction in the total peripheral resistance index (TPRI) of 19% (P less than 0.001). Similar responses were seen supine at rest and during 50W, 100W and 150W bicycle exercise. No significant changes were seen in heart rate. There was a slight increase in stroke index, and cardiac index was preserved at rest and during exercise with a slight trend towards an increase. In 10 of the patients, blood pressure was monitored by a portable blood pressure recorder (Accutracker II, Suntech Medical instruments, Raleigh, North Carolina, USA). Blood pressure was well controlled throughout the full 24 h period after one daily dose. In conclusion, amlodipine exerts a clear antihypertensive effect, both at rest and during exercise, through reduction in the TPRI and without a fall in cardiac pump function. No changes in heart rate were seen and there was no tendency for a reduction in the stroke index during 8 min of exercise at 150 W; on the contrary there was a trend towards an increase. The incidence of side-effects was low (ankle oedema in two patients).

Comparison of the side-effects of pindolol and atenolol in the treatment of hypertension.

A double-blind multicentre study of 349 hypertensive patients was performed to compare the side-effects of the two beta-blockers atenolol (selective beta 1-blocker) and pindolol (beta 1- and beta 2-blocker with Intrinsic sympathomimetic activity (ISA] in equipotential doses (100 mg atenolol vs. 15 mg pindolol). Male and female patients aged 20-65 years with essential hypertension WHO stages I and II were included. Patients were examined 1 and 6 months after the start of treatment, and side-effects were recorded. The antihypertensive effect was similar for the two drugs. After 1 month there was significantly less bradycardia (P less than 0.01), cold hands and feet (P less than 0.05) and tiredness (P less than 0.02) in the pindolol group, and less sleep disturbance (P less than 0.02) in the atenolol group. After 6 months there was no significant difference in sleep disturbance, but the differences in the other side-effects remained significant.

Androgen-oestrogen imbalance in men with chronic alcoholism and fatty liver.

The plasma concentrations of oestrone (E1), oestradiol (E2), oestrone sulphate (E1S), testosterone (T), sex hormone binding globulin (SHBG) and apparent free testosterone (AFTC) were measured in 20 normal-weight men with chronic alcoholism and fatty liver. Twenty normal-weight male blood donors matched for age acted as controls. In the alcoholic subjects (patients) the plasma levels of E1, E2 and SHBG were significantly elevated, whereas the concentrations of E1S and AFTC were significantly decreased. No difference in plasma T was seen between the two groups. Both patients and controls showed a significant correlation between SHBG and E2, whereas a significant correlation between SHBG and T, and between E2 and T, was only found in the controls. Eight of the patients showed signs and/or symptoms of hypogonadism or feminization. Only patients with hypogonadism and/or feminization showed significantly higher plasma levels for E2 and decreased T/E2 ratio than matched controls. The ratio E1S/E1 was in every case lower than in the control and tended to be even lower in the patients with hypogonadism and/or feminization.

Conjugated and unconjugated plasma oestrogens in men with chronic alcoholism and in normal men.

The plasma concentrations for unconjugated and conjugated oestrone, oestradiol-17 beta and oestriol, were measured in 25 male patients with chronic alcoholism and 25 healthy male blood donors of the same age. All persons had normal weight and were free of medication. The patients with chronic alcoholism consisted of 15 persons with and 10 without hepatomegaly. Liver biopsy was performed in the persons with hepatomegaly. Unconjugated oestrogens were separated on LH-20 micro columns after extraction with diethyl ether. Oestrogen sulphates were extracted and separated after hydrolysis with sulphatase, and glucuronides were extracted and separated after hydrolysis with glucuronidase. In the patients with hepatomegaly the plasma concentrations of unconjugated oestrone, oestradiol-17 beta and oestriol were significantly increased, and the plasma levels for the same oestrogen sulphates were significantly decreased, whereas a moderate increase was observed for oestriol glucuronide. The patients without hepatomegaly revealed a significantly lower plasma concentration for oestrone sulphate, whereas no difference was seen for the remaining oestrogen components. The ratio oestrone sulphate to oestrone was significantly reduced in both groups of patients. A significant decrease for the ratio oestradiol sulphate to oestradiol and oestriol sulphate to oestriol was seen only in the patients with hepatomegaly.