Muiesan G

Adrenergic activity and left ventricular function during treatment of essential hypertension with calcium antagonists

The effects of 2 calcium antagonist drugs, verapamil and nifedipine, on blood pressure, heart rate (HR), plasma catecholamines, plasma renin activity and some echocardiographic indexes of left ventricular anatomy and function were studied in 67 patients with essential hypertension. The short- and long-term antihypertensive effect of verapamil was not associated with significant changes in HR, plasma catecholamines or plasma renin activity; the decrease in blood pressure after nifedipine was associated with a significant increase in HR and plasma catecholamines (mainly noradrenaline) (p less than or equal to 0.05). These findings were confirmed in a crossover comparison in 12 hospitalized patients treated with verapamil and nifedipine for 8 days each. The dose of isoproterenol that increased HR by 25 beats/min was significantly increased during verapamil treatment (p less than 0.05) and decreased during nifedipine treatment (p less than 0.01). Stroke volume and shortening fraction increased slightly but significantly (p less than 0.05) with 3 months of nifedipine treatment, while no change was detected with verapamil treatment. Left ventricular mass was significantly decreased after effective antihypertensive treatment for 3 months with verapamil or nifedipine (p less than or equal to 0.05).

Similarities and differences in the antihypertensive effect of two calcium antagonist drugs, verapamil and nifedipine

The short- and long-term effects of two calcium channel blocking drugs, verapamil and nifedipine, on blood pressure, heart rate, plasma catecholamines, plasma renin activity, plasma volume and cardiac performance (echocardiography) were studied in essential hypertensive patients and in normal subjects. Verapamil, 160 mg orally, reduced blood pressure within 60 minutes in 22 hypertensive patients, but not in 12 normotensive subjects. Nifedipine, 10 mg sublingually, reduced blood pressure within 15 minutes in 19 hypertensive patients, but not in 7 normotensive subjects. Plasma noradrenaline was significantly increased both in normal subjects and in hypertensive patients only after nifedipine was administered. Verapamil (80 mg three times a day) first, and nifedipine (10 mg three times a day) thereafter, or vice versa, were given to 12 hospitalized hypertensive patients on a fixed sodium and potassium intake; the drugs produced similar blood pressure reductions, but heart rate and plasma catecholamines were increased only after nifedipine (p less than 0.05). Neither drug affected plasma volume, aldosterone or plasma renin activity. Long-term ambulatory treatment with verapamil (80 or 160 mg three times a day for 2 to 4 months) or nifedipine (10 mg three times a day for 2 months) produced changes in all variables that were similar to those observed in the hospital (controlled) study. Shortening fraction was significantly increased after nifedipine (p less than 0.05) but no change was observed after verapamil. In conclusion, blood pressure is effectively reduced by both verapamil and nifedipine; an appreciable adrenergic stimulation may be caused by nifedipine, but usually not by verapamil, and fluid retention, renin release or myocardial depression is not observed during verapamil or nifedipine treatment.

Relation between cardiac hypertrophy and forearm vascular structural changes before and during long-term antihypertensive treatment

In patients with hypertension, structural changes develop in the heart and in the systemic arteries that have a significant role in the maintenance and gradual worsening of the hypertensive disease. Blood pressure, basal and post-ischemic maximal forearm blood flow (strain-gauge venous occlusive plethysmography), and echocardiographic left ventricular mass index were measured in 28 hypertensive patients (WHO class I or II, 23 men and five women, aged 26 to 59 years). Minimal vascular resistance (mean arterial pressure/peak blood flow) was taken as an index of vascular structural changes. The same measurements were made in a group of 14 patients before and after long-term antihypertensive treatment: in eight patients after six and 12 months of treatment with captopril (50 mg twice a day, plus 25 mg of hydrochlorothiazide per day if necessary) and in six patients after six months of treatment with nitrendipine (20 mg per day, plus 50 mg of atenolol per day if necessary). A significant but weak direct correlation was found between the degree of left ventricular hypertrophy and mean arterial pressure (r = 0.41) or minimal vascular resistance (r = 0.31). Thus, patients were categorized according to whether they had left ventricular hypertrophy or impaired blood flow; the results suggested that left ventricular hypertrophy may be detected earlier than increased minimal vascular resistance. After six months of treatment, both captopril and nitrendipine significantly reduced left ventricular mass index and minimal vascular resistance. Left ventricular mass index was normalized in 50 percent of the patients, whereas minimal vascular resistance was normalized in one patient only. After 12 months of treatment, left ventricular mass index was normalized in all patients; minimal vascular resistance was on the average further reduced but normalized in only one additional patient. Thus, regression of cardiovascular structure also seems to occur earlier in the heart.

Beneficial effects of one year's treatment with captopril on left ventricular anatomy and function in hypertensive patients with left ventricular hypertrophy

This study evaluated by echocardiography (M-mode tracings, two-dimensional-guided) the effects of captopril administration for one year (25 to 50 mg twice a day, alone or in combination with hydrochlorothiazide when necessary) on left ventricular mass index, on systolic function at rest and during stress (hand grip for three minutes and cold pressor test for three minutes), and on diastolic function in 15 patients with essential hypertension (13 men and two women, aged 30 to 67 years) with left ventricular hypertrophy. In addition, supine and standing plasma catecholamine concentrations, plasma renin activity, and plasma aldosterone levels were measured. Examinations were performed during a placebo period and after three, six, and 12 months of captopril treatment. Blood pressure was significantly reduced (p less than 0.001), but heart rate did not change. Left ventricular hypertrophy was progressively reduced during treatment, mainly through reduction of left ventricular wall thickness. After one year, all patients had a normal left ventricular mass index (less than 120 g/m2). Before and during treatment, left ventricular systolic function, at rest and on maximal hand grip and cold pressor testing, evaluated on the basis of fractional shortening as related to end-systolic stress, was within the 95 percent confidence limits (calculated in a group of 25 normal subjects) in all 15 patients with essential hypertension. The percent increase in left ventricular dimensions during the diastolic rapid filling phase was significantly increased by treatment (p less than 0.05), indicating improvement of left ventricular relaxation. As expected, plasma renin activity was increased, plasma aldosterone levels were decreased, and plasma catecholamine concentrations did not change. These results indicate that long-term treatment with captopril has beneficial effects on left ventricular anatomy and function in patients with essential hypertension.

Left ventricular systolic function in relation to withdrawal of different pharmacological treatments in hypertensives with left ventricular hypertrophy

We evaluated the left ventricular mass index (LVMI) and the functional response to cold pressor and handgrip tests in 74 untreated essential hypertensive patients and 26 age and sex-matched normals. The same measurements were repeated in 22 essential hypertensives after 6 and 12 months of treatment (captopril or nitrendipine, plus diuretic or β-blocker in a few cases) and in 21 essential hypertensives after withdrawal of treatment, a reduction in the LVMI and a further increase in blood pressure. Left ventricular systolic function was evaluated by the relationship between left ventricular end-systolic stress and fractional shortening. Highly significant negative correlations, with similar slopes and intercepts, were found between end-systolic stress and fractional shortening under basal conditions, after regression of left ventricular hypertrophy and after withdrawal of treatment, both al rest and at the peak of stress tests. An examination of each point of the relation between end-systolic stress and fractional shortening showed that very few points were beyond the 95% prediction limits of the correlation obtained in normal volunteers. These results indicate that left ventricular systolic function is normal in most untreated essential hypertensives, and is usually well maintained after regression of left ventricular hypertrophy during long-term treatment as well as after withdrawal of treatment, both at rest and during an acutely induced afterload increase.

Effect of enalapril on parasympathetic activity.

SummaryTo evaluate the effect of converting enzyme inhibition induced by enalapril on parasympathetic activity, we studied ten essential hypertensive patients, age range 38–58 years, WHO I–II. Parasympathetic evaluation was obtained by measuring the variation of heart period (VHP) during at least 1 minute of steady-state, regular respiration. VHP was derived from the difference between the mean of all maximum and the mean of all minimum heart periods. The higher the VHP, the higher the parasympathetic control of heart rate and vice versa. VHP was measured supine and with tilting (30°, 60°, 85°). Blood pressure was reduced after 1 month of enalapril treatment, while the heart rate did not change. VHP increased at the end of enalapril treatment compared with placebo: in the supine position it increased from 36±3.2 ms to 44±3.5 ms, p<0.01. VHP was also increased by enalapril at 30° (p<0.05) and 60° (p<0.05), while no difference was observed at 85° between placebo and enalapril. A positive correlation was found between supine enalapril changes of VHP and those of systolic and diastolic BP. In conclusion, enalapril seems to increase parasympathetic cardiovascular control in essential hypertensive patients. This result might explain the lack of increase in heart rate that would be expected as a result of the vasodilating effect of enalapril.

Possibility of Cardiac Output Monitoring from the Intra-Arterial Blood Pressure Profile

A method for estimating cardiac output (CO) from the intra-arterial blood pressure profile (contour method) was tested in 8 patients: 6 with essential hypertension, 1 with a pheochromocytoma and 1 with orthostatic hypotension. CO (1/min) was derived by the following formula: PSA (1+St/Dt) X HR 10(-3), where PSA is the area under the systolic portion of the pressure curve, St is the systolic and Dt the diastolic time, X is a correction factor, HR is the heart rate and 10(-3) is a conversion factor from ml/min to 1/min. The contour method was compared to the thermodilution CO method. The correlation between the 2 methods was highly significant: the r value in all patients during different conditions (supine, tilt, dynamic and static exercise) ranged from 0.91 to 0.97 with an intercept close to 0 and a slope close to 1. These results indicate that CO is properly measured from the intra-arterial blood pressure profile by the contour method. A continuous hemodynamic monitoring can be derived applying the contour method to the intra-arterial blood pressure profile obtained with the Oxford technique.

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.