Relationship of plasma renin activity and aldosterone levels with hemodynamic functions in essential hypertension.

Correlates of plasma renin activity and plasma aldosterone levels with hemodynamic functions were studied in 47 male patients with untreated, permanent essential hypertension. All subjects had a normal creatinine clearance and received a diet of 110 mEq/day of sodium. Supine plasma renin activity was directly correlated with cardiac index (P less than.01) and cardiopulmonary blood volume (P=.01). Percentage changes in plasma renin activity and total peripheral resistance in response to upright position were positively correlated (P less than.001). Supine plasma aldosterone level was directly correlated with stroke index (P less than .001) and negatively correlated with hear rate (P less than .05). No significant correlation of aldosterone level was observed with the other measurements, including plasma renin activity. The study points to the neural sympathetic control of plasma renin activity in essential hypertension and suggests the existence of some interrelationships between aldosterone level and cardiac performance.

Essential hypertension: an approach to clinical data by the use of models.

A new approach, based on animal circulatory models, was proposed for the study of clinical data in hypertension. Clinical data were identified with steady states in models. From the study of models, possible impairments, susceptible to account for the observed derivations of steady states in men, were analyzed. To be specific, the 1967-Guyton-Coleman model was confronted with a set of data on essential hypertension. The approach afforded a physiological interpretation for statistical results performed on clinical data.

Tilt test in essential hypertension. Differential responses in heart rate and vascular resistance.

Changes in hemodynamic parameters following 50-degree head-up tilt were studied in a population of 56 men, including 35 subjects with sustained essential hypertension and 21 age-matched normotensive controls. The increase in heart rate following tilt was similar in groups and exhibited the same reduction in response with age. The increase in vascular resistance following tilt was strongly and positively correlated with both age and baseline vascular resistance. The latter finding was observed mainly in hypertensive subjects. The study provided evidence that differentiated responses of heart rate and vascular resistance may be observed following orthostasis. In both normal and hypertensive subjects, the age dependence of heart rate response possibly reflected differences in baroreceptor reflex control of parasympathetic and sympathetic activity. In hypertensive subjects, the vascular response was amplified with age and baseline vascular resistance, suggesting a role for structural changes of the vessels in the increased vascular response.

Guanfacine kinetics in patients with hypertension.

Guanfacine kinetics were studied in 19 patients with hypertension after single and repeated oral doses. The single-dose study was performed in two homogeneous groups who received 2 mg (n = 9) and 4 mg (n = 10). The plasma concentrations were fitted in a two-compartment open model with first-order absorption. After a lag time of 0.8 hr, the absorption occurred rapidly (t 1/2 congruent to 0.53 hr). The fast and slow elimination phases occurred with t 1/2s of 2 and 19 hr. At therapeutic levels the percent of drug in red blood cells (55%) was independent of total drug concentration. Peak plasma levels had small interindividual variations. Comparison of kinetic parameters and AUC at the two doses studied demonstrated that their bioavailability was equal and the kinetics were linear. In a multiple-dosing study, performed in the same subjects, the plasma levels at steady state were in good agreement with the predicted values (p less than 0.001) and proportional to daily dosage. A single method based on four blood samples collected after 24, 28, 32, and 36 hr allows a reasonable prediction of the effective steady-state plasma levels during chronic dosing with guanfacine.

Pindolol availability in hypertensive patients with normal and impaired renal function.

Intravenous and oral pharmacokinetics of pinlolol were studied in 18 hypertensive patients-9 with normal renal function and 9 with impaired renal function. Analysis of data showed that a linear two-compartment model was suitable to describe the pindolol kinetics. Compared with patients with normal renal function, patients with chronic renal failure exhibited: (1) unchanged transfer rate constants and distribution volumes and (2) decreased total body clearance with decreased renal clearance and unchanged nonrenal clearance. Analysis of oral data by the Loo-Riegelman method showed that the pindolol absorption kinetic was not first order. Compared with patients with normal renal function, patients with chronic renal failure exhibited decreased fraction of dose effectively absorbed and increased initial rate of absorption. The initial rate of absorption was inversely correlated with the creatinine clearance. The study disclosed evidence that absorption was modified in chronic renal failure.

Repeat hemodynamic determinations in borderline hypertension.

Repeat hemodynamic determinations were performed in 37 young men with borderline hypertension. The duration of the follow up study was 47 +/- three months. At each determination, those with borderline hypertension were compared to a group of matched normal subjects. Blood pressure increased from the first to the second determination, but the increase was significant only for systolic (P less than 0.001) and mean (P less than 0.01) arterial presssures. Cardiac index and heart rate, which were initially increased, decreased significantly (P less than 0.02; P less than 0.01, respectively) and decreased to normal values; total peripheral resistance increased (P less than 0.01); blood and plasma volumes decreased (P less than 0.01). At the first determination, the cardiac index-heart rate correlation was significant (P less than 0.01) and the cardiac index-blood volume correlation was not. At the second determination, on the contrary, the cardiac index-total blood volume correlation was significant (P less than 0.001) whereas the cardiac index-heart rate correlation was not. The study provides evidence that patients with borderline hypertension, over a short-term period, show (1) a greater increase in systolic than in diastolic pressure, (2) a return of cardiac output toward normal values through a decrease both in heart rate and blood volume, and (3) an increased importance of volume factors in the cardiac output control.

Ventricular arrhythmia in Duchenne muscular dystrophy: prevalence, significance and prognosis.

The prevalence and prognostic value of ventricular arrhythmias were examined in 45 Duchenne muscular dystrophy patients without congestive heart failure and followed up for 3 yr. Baseline evaluation included 24 h ECG monitoring, systolic time intervals measurement (preejection period/left ventricular ejection time PEP/LVET), echocardiogram and vital capacity tests. Fifteen patients (33%) had ventricular premature beats (VPB > or = 2 h-1). More complex ventricular ectopy (Lown grades 3, 4A, 4B) occurred in 12 patients (27%), who had abnormal ventricular contractility (PEP/LVET > 0.48) and an area of akinesia or dyskinesia. Complex VPB were present on presentation in only 3 of the 30 survivors (10%) but were detected in 6 of the 15 patients (40%) who died. Patients who died suddenly were more likely to have had documented complex ventricular arrhythmias (6 of 9; 66%). It is concluded that: (1) significant arrhythmias frequently coexist with asymptomatic left ventricular dysfunction and wall motion abnormalities; (2) complex VPB as well as left ventricular dysfunction and dilated cardiomyopathy are risk factors for sudden death.

Control of cardiac output in essential hypertension.

Cardiac and renal hemodynamics and cardiopulmonary and total blood volume were determined in 202 men, 101 with normotension and 101 of the same age with chronic essential hypertension, normal renal function and balanced sodium intake and urinary output. Cardiac output was identical in the two groups, whereas blood pressure and total peripheral resistance were significantly different. The two groups exhibited strong differences in the correlation study: (1) Correlations of blood pressure with, respectively, heart rate, cardiopulmonary blood volume and total blood volume were significant in the normotensive group but not in the hypertensive group. (2) Correlations of cardiac output with, respectively, heart rate, cardiopulmonary blood volume and total blood volume were significant in both groups. (3) Correlations of renal blood flow with, respectively, cardiac output, blood pressure and total blood volume were significant in the hypertensive group but not in the normotensive group. This study provides evidence that: (1) the volume and neural control of blood pressure are disrupted in hypertension whereas control of cardiac output is maintained; and (2) adaptive mechanisms involving renal function are necessary to the maintenance of normal cardiac output in patients with essential hypertension.

Difference in response of vascular resistance to orthostasis in patients with borderline and sustained essential hypertension.

Changes in hemodynamic parameters following 50-degree head up tilt were studied in a population of 78 males, including 30 patients with sustained essential hypertension, 30 patients with borderline hypertension, and 18 normotensive controls of the same age. The increase in vascular resistance following tilt was significantly higher in hypertensive subjects. In patients with sustained hypertension, baseline vascular resistance was significantly higher than in normotensive controls, and it was strongly correlated with its change following orthostasis. In patients with borderline hypertension, baseline vascular resistance was similar to that of normotensive controls and did not correlate with its change following orthostasis. The latter result suggests an abnormality in the autonomic nervous control in patients with borderline hypertension, possibly mediated by cardiopulmonary mechanoreceptors in the low pressure system.

Renal and systemic hemodynamics in borderline hypertension.

Cardiac output (CO), renal blood flow (RBF), and glomerular filtration rate were measured in 29 young patients with borderline hypertension, in comparison with 26 normotensive controls of the same age and sex. In patients with borderline hypertension, both CO and RBF were significantly increased, whereas the RBF/CO ratio remained within the normal range. No significant changes in glomerular filtration rate and renal filtration fraction were observed. The study clearly demonstrated that renal ischemia was absent in young patients with borderline hypertension.

Antihypertensive effects and plasma levels of guanfacine in man.

The antihypertensive effect and the plasma levels of guanfacine were studied for two months in 25 patients with sustained essential hypertension. In three patients, blood pressure was unchanged. In ten patients, blood pressure returned to the normal range within 15 days, at a daily dose of 2 mg. In 12 patients, increasing doses were necessary to normalize the blood pressure within two months. In these cases, the decrease in systolic pressure was negatively correlated with the daily dose of guanfacine (r = -0.40) and the steady-state plasma level (r = -0.62; P less than 0.01); analysis of the curves showed that the normalization of blood pressure coincided with a plasma drug level of 8 ng/ml, i.e., a 4-mg daily dose. This study demonstrated the efficacy of guanfacine monotherapy in hypertension and suggests that the normalization rate of blood pressure levels does not further increase with daily doses higher than 4 mg.

Isoproterenol sensitivity and total body clearance of propranolol in hypertensive patients.

The isoproterenol sensitivity (dose-response curve) and the total body clearance of propranolol were measured in 80 men including 15 normal subjects and 65 essential hypertensive patients (20 borderline and 45 permanent hypertensives). The critical dose of isoproterenol was found to be directly correlated to weight (P less than 0.01), age (P less than 0.001), and basal diastolic arterial pressure (P less than 0.001). A partial correlation coefficient study showed that the diastolic arterial pressure was of greater influence than weight and age. The total body clearance of propranolol was inversely related to the basal diastolic arterial pressure (P less than 0.0001) in hypertensive patients. The study provides evidence that the level of basal diastolic arterial pressure could influence the beta-receptor responsiveness and the beta-adrenergic blockade in hypertensive patients.

Pharmacokinetics and hepatic extraction ratio of pindolol in hypertensive patients with normal and impaired renal function.

The intravenous and oral pharmacokinetics and the hepatic extraction ratio of pindolol were determined in 24 hypertensive patients with normal or impaired renal function. In patients with normal renal function, the total clearance was the sum of equal parts of the renal and nonrenal clearances. The nonrenal clearance was found to be equal to the hepatic clearance directly measured from the hepatic extraction ratio. Compared to patients with normal renal function, patients with chronic renal failure exhibited (i) unchanged K12 and K21 and nonrenal clearances, and (ii) significantly decreased values in half-life of the beta phase, Kel, and total renal clearance. The renal clearance was positively correlated (P less than 0.01) to the creatinine clearance. Bioavailability was significantly reduced (P less than 0.01) in the patients with renal failure. Assuming that the nonrenal clearance was equal to the hepatic clearance, the study provides evidence that, in patients with renal insufficiency, (i) no increased metabolism accompanies the decrease in renal function, and (ii) decreased availability is due to reduced absorption.

Overhydratation and renin in hypertensive patients with terminal renal failure: a hemodynamic study.

Twenty-nine patients with terminal renal failure were treated by periodic hemodialysis for 2 to 18 months. Serial determinations of blood pressure, blood volume, cardiac output, exchangeable sodium and plasma renin activity were performed. Bilateral nephrectomy was performed in 17 patients and followed by a fall in blood pressure. Cardiac index was elevated in all patients but the blood pressure changes were mainly related to resistance changes. In non-nephrectomized patients, mean arterial pressure was directly correlated to plasma volume (P less than 0.0001), exchangeable sodium (P less than 0.01) and plasma renin activity (P less than 0.001). In anephric patients, mean arterial pressure was only directly correlated to plasma volume (P less than o.005). The slope of the curve relating arterial pressure to plasma volume was significantly shallower in nephrectomized than in non-nephrectomized patients, indicating a lower sensitivity of pressure to volume changes. The study provides evidence that, in hypertensive patients with chronic renal failure, the positive pressure-volume relationship is the fundamental cause of the high blood pressure and that the renin-angiotensin system acts mainly by changing the sensitivity of this mechanism.

Systolic time intervals in Duchenne muscular dystrophy: evaluation of left ventricular performance.

The purpose of this study was to evaluate the prevalence of latent cardiac heart failure in Duchenne's muscular dystrophy (DMD). Systolic time intervals (STI) were measured in a cross-sectional study of a group of 177 patients 6-21 years old. Total electromechanical systole (QS2), left ventricular ejection time (LVET), and pre-ejection period (PEP), were corrected for heart rate by means of regression equations obtained from 33 normal subjects (QA2 I, LVET I, PEP I). Mean STI values were significantly different from those observed in an age-matched control group. PEP I was prolonged, LVET I was abbreviated, while QS2 I remained unaltered. STI varied significantly with age. Abnormal values were uncommon before age 10 years. The most critical period was 14-16 years, with an abrupt increase in prevalence from 35 to 72%. Such changes point to the practical use of the STI for clinical decision making especially for surgery.

Arterial compliance in permanent essential hypertension: preliminary report.

Systemic arterial compliance was measured in 22 patients with permanent essential hypertension and compared with 11 sex- and age-matched normal normal subjects. Determinations were made from analysis of the monoexponential blood pressure-time curve during diastole, according to a simple visco-elastic model. Arterial compliance was significantly decreased (P less than 0.001) in hypertensives. In the overall population, arterial compliance was negatively correlated to age (P less than 0.005) and blood pressure (P less than 0.001), suggesting that the changes in compliance could be attributable to the level of blood pressure per se and/or to the rigidity of the arterial wall. Administration of vasoactive substances (angiotensin and sodium nitroprusside) enabled a strong negative relationship (P less than 0.01) between arterial compliance and diastolic blood pressure to be demonstrated in each individual. The slope of the curve was not dependent on age and represented the ability to decrease compliance per unit rise in pressure. The slope was steeper in hypertensives, suggesting a change reactivity of the arterial wall in these patients.

Hemodynamic effects of the anti-hypertensive agent ketanserin in hypertension in man.

The hemodynamic changes caused by ketanserin, an anti-hypertensive agent with S2-serotonergic receptor and alpha 1-adrenoceptor blocking properties, are reviewed in patients with essential hypertension. The hemodynamic profile associates a decrease in total peripheral resistance, an unchanged cardiac output, and a modest reflex cardiac stimulation. Whether the drug reverses the other hemodynamic abnormalities of essential hypertension, such as reduced arterial and venous compliances and increased cardiac mass, remains largely unknown. Evaluation of the changes in arterial and venous systems will be important in the view that the pharmacological profile of ketanserin could be involved in the modifications of the arterial wall observed in hypertension and atherosclerosis.

[Problems in practical management of essential hypertension]. / L'hypertension artérielle essentielle. Problèmes de conduite pratique.

A study of 100 men with arterial hypertension showed that: 1) hypertension was predominantly moderate with 14% index of placebo reactivity; 2) only 3 patients had a surgically curable etiologic factor; 3) frequent associated findings were hereditary factors (60%), overweight and metabolic disorders (30 to 40%). Such results suggest that: a) hypertension could be treated, in the majority of patients, without preliminary etiologic investigations and, b) non invasive hemodynamics techniques are required to evaluate arterial and cardiac lesions which are the dominant factors in the prognosis.