Unchanged central hemodynamics after six months of moderate sodium restriction with or without potassium supplement in essential hypertension.

Sodium (Na) restriction and potassium (K) supplementation has been recommended as treatment of essential hypertension but the mechanism by which these may reduce blood pressure (BP) is unknown. We examined if moderately reduced Na intake, combined with a low-Na/high-K salt alternative (Pansalt: NaCl 57%, KCl 28%, MgSO4 12%) as substitute for standard table salt, induced clinically significant BP reduction in hypertensive patients and, if this therapy reduced total peripheral resistance. After a 2-month control period 40 patients aged 21-67 years with mean casual BP 156/103 mmHg were given a salt restricted diet (120 mmol Na/24 h) for 6 months. In addition, they were randomised in a double-blind manner to receive either Pansalt (P-group) or standard NaCl (S-group) as table salt in small amounts. Cardiac output was measured by dye dilution. Daily Na excretion was similarly reduced (20%) in both groups while K excretion was slightly increased in the P-group and reduced in the S-group (difference p < 0.05). No large changes occurred in 24-h ambulatory BP (by Accutracker II) or intraarterial pressure (through a brachial artery catheter) at rest or during exercise while casual BP was reduced (p < 0.05) 13/8 mmHg in the P-group and 8/5 mmHg in the S-group. While cardiac output was slightly reduced at rest and during 50W exercise in the P-group, no significant changes were seen in total peripheral resistance in either group. Thus, moderate reduction in Na intake, with or without addition of K, is not sufficient to induce significant long-term intraarterial or 24-h ambulatory BP changes in essential hypertension. Without BP changes invasively determined central hemodynamics remains remarkably stable over a 6-month period.

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).

Nisoldipine. Central haemodynamics at rest and during exercise in essential hypertension: acute and chronic studies.

Calcium blockers may reduce contractility of vascular smooth muscle as well as that of myocardial cells. Therefore, falls in both total peripheral vascular resistance (TPR) and cardiac output (CO) might be responsible for a fall in blood pressure (BP) caused by calcium blockers in essential hypertension. We have studied the acute and chronic haemodynamic effects of nisoldipine (a new calcium blocker) in 19 patients with essential hypertension at rest in the supine and sitting positions and during 100-W dynamic exercise to investigate whether CO might be compromised by acute and chronic calcium blockade. Intra-arterial pressure, CO (by Cardiogreen), stroke volume, heart rate and TPR were measured hourly after the first dose of 10 mg nisoldipine (acute study) and then after 1 year of nisoldipine treatment (mean dose 25 mg; chronic study). The maximal first dose response was seen after 1 h, i.e. a fall in intra-arterial pressure (9%) and TPR (19%) and a reflex rise in heart rate (9%) and CO (12%). The effects levelled off during the next 2 h. After 1 year of treatment there was a more marked reduction in BP: at rest intra-arterial pressure fell (14% supine, 16% sitting) due to fall in TPR (19%) but without significant changes in heart rate or CO; during 100-W exercise, intra-arterial pressure fell (14%) due to reduction in both TPR (7%) and CO (6%). In conclusion, nisoldipine lowers BP by reducing TPR, both acutely and chronically. The initial reflex tachycardia and rise in CO disappear during long-term treatment, probably due to resetting of the baroreceptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Central hemodynamic changes of calcium antagonists at rest and during exercise in essential hypertension.

Since the cardinal hemodynamic disorder in essential hypertension is an increased total peripheral resistance, drugs that can lower resistance without reducing blood flow would be particularly useful. The calcium antagonists seem to fulfill this criterion. The purpose of this work was to study the hemodynamic effects at rest and during exercise of three calcium channel blockers, verapamil, nifedipine, and nisoldipine, in patients with mild to moderate essential hypertension. Fifty-four patients aged 20-64 years with pretreatment diastolic blood pressures of between 95 and 120 mm Hg were studied at rest and during exercise on an ergometer bicycle. Blood pressure was recorded intraarterially and cardiac output was measured by Cardiogreen. After the initial study, 10 patients were treated with verapamil (40-80 mg three times daily), 15 with nifedipine (long-acting form, 20-80 mg daily), and 19 with nisoldipine (10-40 mg daily). After 1 year the hemodynamic study was repeated. The immediate response to the first dose was studied in the patients taking nisoldipine and in 10 patients after taking placebo tablets. Placebo induced no significant changes in central hemodynamics during the first 3 h after tablet intake. The calcium antagonists induced a reduction in blood pressure and in total peripheral resistance (in the order of 10-18%) without any reduction in cardiac index. Reflex tachycardia and an increase in cardiac output were seen in the first 2 h after the first dose of nisoldipine, but after 1 year the heart rate was unchanged compared with the pretreatment rate at rest and during exercise. In contrast, heart rate was reduced on verapamil treatment, particularly during exercise (about 10% of patients), but this was compensated for by an increase in the stroke volume. The hemodynamic profiles of the three calcium channel blockers were slightly different, especially with respect to the heart rate response. Total peripheral resistance was reduced, acutely as well as chronically, and no depression in cardiac pump function was seen, either at rest or during exercise.

Central hemodynamic effects at rest and during exercise of acute and chronic treatment with nisoldipine in essential hypertension.

The acute and chronic hemodynamic effects of nisoldipine were studied in 19 patients (17 men, 2 women; mean age 43 years) with essential hypertension at rest supine and sitting and during steady state 100 W bicycle exercise. At rest supine, the first dose response (1 h) was reduction of intraarterial (IA) pressure (9%) and total peripheral vascular resistance (TPR; 19%) and rise in heart rate (HR; 9%) and cardiac output (CO; 12%). Thereafter, the effect leveled off: at 3 h, IA pressure, CO, and TPR were reduced 6%, 1%, and 4%, respectively. Similar results were seen at rest and during exercise. After 1 year treatment, the changes were more marked: at rest, IA pressure and TPR fell (16% and 20%, respectively) while stroke volume and CO rose slightly (4% and 6%, respectively). There was no reflex tachycardia. During 100 W exercise, IA pressure fell (14%) due to reduction both in TPR (7%) and CO (6%). Thus, at rest, nisoldipine lowers blood pressure by reduction of TPR both acutely and chronically. The initial rise in CO is lost after long-term therapy. During exercise, falls in both TPR and CO contribute to the hypotensive effect.