[The vascular renin-angiotensin system and hypertension].
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Angiotensin-Converting Enzyme Inhibitors↗
Biomedical subjects
M Safar
Publications and source records attributed to M Safar.
Sodium and large arteries in hypertension. Effects of indapamide.
Epidemiologic studies evaluating arterial pulse wave velocity together with blood pressure indicate that: (1) salt intake has an independent effect on arteriolar tone and arterial wall properties, with the former indirectly and the latter directly contributing to increased arterial stiffness with age; and (2) normotensive adult subjects who follow a low sodium diet have reduced arterial stiffness and this effect is independent of blood pressure. Conversely, in elderly persons with isolated systolic hypertension, isotonic saline infusion causes a predominant increase in systolic pressure due to an increase in the stiffness of the arterial wall. The diuretic indapamide produces a decrease in blood pressure without significant change in brachial artery diameter. The result indicates a shift of the pressure-diameter curve, reflecting for the first time in humans a pharmacologic effect of the drug on arterial vessel. Furthermore, diuretic drugs may increase arterial distensibility and compliance in hypertensive patients, but this effect seems to be more pronounced in older than in younger subjects. In the latter, either activation of the sympathetic nervous system or potassium depletion, or both, might counteract the improvement in arterial distensibility caused by blood pressure reduction and sodium depletion. Based on epidemiologic, clinical, and pharmacologic studies, this critical review suggests that, in patients with essential hypertension, changes of sodium intake in diet or administration of diuretics, or both, affect the status of large arteries independently of blood pressure changes.
Aging↗
Therapeutic trials and large arteries in hypertension.
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Antihypertensive Agents↗
Converting enzyme inhibition and the common carotid circulation in older patients with sustained essential hypertension.
Arterial diameter, blood flow and vascular resistance of the common carotid artery were studied using a pulsed Doppler system in patients with uncomplicated sustained essential hypertension and compared with age-matched normal subjects. In hypertensive patients below the age of 45 years, arterial diameter and blood flow remained within the normal range, while vascular resistance was increased. In hypertensive patients over 45 years of age, arterial diameter was also normal, but blood flow was reduced and vascular resistance markedly increased. Thus, both small and large arteries were altered in the common carotid circulation of patients with sustained essential hypertension. Acute oral administration of converting enzyme inhibitor produced dilatation of both small (vascular resistance) and large (arterial diameter) arteries in the carotid circulation. In addition, in older patients, blood flow significantly increased and vascular resistance markedly decreased both in acute and long-term situations. Thus converting enzyme inhibition was able to reverse the abnormalities of the common carotid circulation of older subjects with sustained essential hypertension.
Adult↗
Non-invasive ultrasonic study of maximal aortic blood acceleration in patients with borderline and sustained essential hypertension.
Using a pulsed Doppler method to evaluate the aortic velocity curve transcutaneously, the maximal aortic blood acceleration was evaluated in normal subjects and in age-matched patients with borderline and sustained essential hypertension. Maximal aortic blood acceleration was significantly elevated in patients with borderline hypertension and remained within the normal range in patients with sustained hypertension. Since maximal aortic blood acceleration is relatively insensitive to preload and afterload, these findings might give indirect information on the contractile state of the myocardium in patients with hypertension.
Adult↗
Flow-dependent vasodilation of the brachial artery in essential hypertension: preliminary report.
Brachial artery haemodynamics including brachial artery diameter and local blood flow velocity were studied in 10 normotensive subjects and 10 age-matched hypertensive patients. A bidimensional pulsed Doppler system was used at rest, during a 2-min period of distal circulatory occlusion and during reactive hyperaemia. The kinetics of changes in blood flow velocity and brachial artery diameter were determined during successive and reproducible manoeuvres. The two parameters decreased significantly during distal artery occlusion in both groups. During reactive hyperaemia, blood velocity reached similar maximal values in both groups and brachial artery diameter increased significantly in both normotensives and hypertensives. Changes in the brachial artery diameter during reactive hyperaemia were positively and significantly correlated to changes in blood flow velocity recorded at the same level. No significant difference was found between normotensives and hypertensives. This study has provided a demonstration of velocity-dependent variations in the diameter of a large artery in humans; the results suggest that velocity-dependent vasodilation of the brachial artery is not impaired in essential hypertension.
Blood Flow Velocity↗
Hemodynamics of the carotid artery after vasodilation in essential hypertension.
We performed simultaneous noninvasive measurements of common carotid artery and brachial artery hemodynamics in nine normal subjects and 10 subjects with sustained essential hypertension. In hypertensive subjects, brachial artery blood flow and forearm vascular resistance were in the normal range while carotid artery blood flow and carotid artery resistance were decreased and increased, respectively. The most important findings were the changes in the internal caliber of large arteries. Although the brachial and carotid artery diameters of hypertensive subjects were measured for the same level of mean arterial pressure, brachial artery diameter was significantly increased and carotid artery diameter was strictly normal as compared with values found in normal subjects. To assess whether carotid artery circulation could influence the baroreceptor reflex response to arteriolar vasodilation, carotid artery and brachial artery hemodynamics were measured in immediate succession in normotensive and hypertensive subjects before and after oral administration of cadralazine, a dihydralazine derivative. After cadralazine treatment, carotid artery tangential tension decreased in hypertensive subjects, and the changes were significantly correlated to the increase in heart rate. A similar correlation was found in normal subjects, but it was reset toward higher heart rates. These results indicate that the carotid artery does not behave like the brachial artery in response to a chronic increase in blood pressure. This behavior indicates intrinsic alterations of the arterial wall and might be involved in the resetting of the carotid baroreceptor reflex. Carotid artery circulation could play a role in hypertension by modulating the carotid baroreceptor mechanisms involved in the response to drug-induced arteriolar vasodilation.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Effects of chronic inhibition of converting enzyme on mechanical and structural properties of arteries in rat renovascular hypertension.
The effect of hypertension and of therapy by converting enzyme inhibitor (S 9490-3, perindopril) on the function and structure of large arteries has been studied in two-kidney, one-clip Goldblatt hypertensive rats. After one month without treatment, clipped hypertensive rats (n = 24) and sham-operated rats (n = 24) were randomly allocated to treatment by S 9490, 1 mg/kg once a day (n = 24) or to placebo (n = 24) and pursued for 4 weeks. Hemodynamic parameters, including instantaneous pressure and aortic velocity measured by Döppler, were recorded under anesthesia at the end of the treatment period. Passive mechanical properties of carotid arteries were recorded in situ in the presence or the absence of smooth muscle cell activity (potassium cyanide poisoning). Morphological parameters of the aortic media, including medial thickness, nucleus density, and cross sectional area and relative density in proteins of interstitial matrix, were recorded by an automated morphometrical system. Hypertension was associated with an increase in characteristic impedance of the aorta and a decrease in compliance of the arterial system. Treatment with converting enzyme inhibitors completely reversed these in vivo markers of the rigidity of large arteries. Hypertension was associated with a shift of the passive pressure-volume relation in the carotid. Treatment with converting enzyme inhibitors normalized the carotid pressure-volume relation, whereas poisoning smooth muscle cells induced a disappearance of the curve differences between hypertensive and normotensive animals. Morphometric analysis of aortic walls permits us to report this functional change to structural modification of the arterial wall. Aortic media thickness was increased by hypertension; this phenomenon was reversed by treatment. Modification of aortic thickness was due to hypertrophy of smooth muscle cells with parallel modifications of absolute amount of collagen, whereas absolute amount of elastin did not change in this early phase of renovascular hypertension in young rats. Treatment with converting enzyme inhibitors reversed the thickness of aortic media without regression of the increase in absolute amount of collagen content whereas absolute amount of elastin content did not change.
Angiotensin-Converting Enzyme Inhibitors↗
Comparison of ketanserin with captopril in older hypertensives. A double-blind randomised trial.
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Aged↗
[Effects of beta-blockers on hemodynamics of the forearm after tobacco stimulation].
In mild hypertension, a betablocker treatment could reduce cardiovascular events. But in smoking men the benefit disappears and this interaction is unexplained. In 6 healthy non smoking men, we studied the effects of acute oral administration of propranolol (80 mg) pindolol (15 mg) and placebo after cigarette smoking (CS) (two cigarettes within 10 minutes). In a double blind cross over randomized study, arterial pressure and heart rate (HR) were recorded within 20 minutes after CS. Brachial artery diameter (D), Local vascular Resistance (RL), Local arterial Compliance (CL) and pulse wave velocity (VOP) were determined non invasively (using a pulsed doppler system) before and 20 mn after CS. Under placebo, mean arterial pressure (PAM), HR and RL increased significantly after CS (+9.2 +/- 3 mmHg, +4.5 +/- 3 b/mn and +36 +/- 14 per cent, respectively). These modifications were not different after propranolol, pindolol or placebo (ANOVA). Arterial distensibility (CL) was decreased after CS and this alteration was not prevented by beta-blockers. Brachial artery diameter was not modified after CS. Our results demonstrate that acute treatment with non selective beta-blockers with or without sympathomimetic intrinsic activity does not prevent haemodynamic modifications induced by cigarette smoking.
Adrenergic beta-Antagonists↗
[Non-invasive ambulatory blood pressure measurement over 24 hours: effects of labetalol on the rise of blood pressure in the early morning].
Three french specialist centers have included 19 hypertensive patients in an open cooperative study of the effect of labetalol (L = 200 to 400 mg b.i.d.) on the 24 hour blood pressure (24 h - B.P.) recording by a non invasive method (Spacelabs - Squibb Medical Systems), with a particular assessment of the early morning rise of BP. Each patient was subjected to 2 assessments at the end of a 14 days' placebo period and of a 28 days' treatment period. At the end of the study, the systolic (SBP) and diastolic (DBP). B.P. were significantly decreased at rest (p less than 0.001) and on the 24 hours recording (p less than 0.001). The reduction of B.P. was also significant on day period from 7 a.m. to 22 p.m. (p less than 0.001) and night period from 22 a.m. to 7 a.m. (p less than 0.05) as well as on the early morning period, 3 hours before and after waking (p less than 0.001). The heart rate was significantly reduced during the day (p less than 0.05) and was not on the night. The slope of the early morning rise of B.P. was marked after placebo and significantly decreased after labetalol with a reduction of 52% for SBP and 49% for DBP (p less than 0.001). These results show that labetalol has an antihypertensive effect over 24 hours with a marked effect on the early morning rise of B.P.
Adult↗
[Pulse wave velocity and ambulatory blood pressure in essential arterial hypertension].
Cardiovascular morbidity and mortality of hypertensive patients is mainly related to lesions of large arteries. Arterial distensibility estimated by carotid-femoral pulse wave velocity (PWV) was evaluated in 22 patients with sustained essential hypertension, together with three different methods of blood pressure (BP) measurement: mercury sphygmomanometer, semi-automatic BP recording using the Dinamap apparatus and 24 H ambulatory BP monitoring using the Spacelabs Monitor (5200). Table shows that, while PWV was not correlated with BP measured by mercury sphygmomanometer, it was strongly and positively correlated with BP measured by the other procedures. The best correlation coefficient was noted for the systolic BP measured in the Day Time (7 h-22 h) by the ambulatory method. This study shows that BP Monitoring correlates more strongly than clinic or casual BP with indices of target organ damage. (Table: see text).
Adult↗
[Pulse pressure and echocardiographic parameters in essential arterial hypertension].
UNLABELLED: We measured systolic, diastolic, mean (MAP) and pulsed (PP) arterial pressures (Dinamap 845 XT), carotid femoral pulse wave velocity (PWV) and cardiac parameters (echocardiography) to evaluate myocardiac mass and indexed cardiac mass to body surface area (IM) in 47 subjects (11 normotensives and 36 with sustained essential hypertension). Hypertensives were allocated between two groups with same age, weight and height, same mean arterial pressure (119.8 +/- 9.1 mmHg, 119.7 +/- 11.9 mmHg, NS) and PWV (11.90 +/- 2.20 m/s, 12.51 +/- 1.83 m/s, NS): group I (22 subjects) with pulsed pressure less than 60 mmHg, group II (14 subjects) with pulsed pressure greater than or equal to 60 mmHg. (Table: see text). Newman-Keuls between group I and group II: p less than 0.01 for cardiac mass and IM, p less than 0.001 for PP. Cardiac mass (p less than 0.01) and indexed mass to body surface area (p less than 0.01) were greater in group II (with pp greater than or equal to 60 mmHg) than in group I. CONCLUSION: arterial hypertension is linked with left ventricular hypertrophy which is increased when pulsed pressure is enhanced. This fact could give evidence of importance of pulsatory work in cardiac consequence of hypertension.
Adult↗
[Non-invasive measurement by Doppler pulse of cardiac output and maximal aortic acceleration in essential arterial hypertension].
Three groups of 11 male subjects with the same mean age were studied: normotensives (group I), patients with sustained essential hypertension (group II) and patients with borderline hypertension (group III). M-mode echocardiography provided a measure of aortic root systolic diameter (D) and left ventricular mass index (LVMi, g/m2). We have used a 4 MHz pulsed doppler velocity meter with spectral analysis to measure instantaneous ascending aortic blood velocity. Measurements values were averaged during 10 s and included: stroke volume (SV, cm3 = integrated velocity over one cardiac cycle.aortic cross sectional area (3.14D2/4)), cardiac output (CO, cm3 = SV.heart rate), systemic vascular resistance (SVR, mmHg/cm3.s-1 = MAP/co) and maximal aortic acceleration (MA, cm/s2). (Table: see text). Stroke volume and cardiac output were similar in three groups. SVR was higher in group II than in group I. The myocardial contractility appreciated from the maximal aortic acceleration (Bennett et al, Cardiovasc Res 1984; 18: 632-8) was increased in patients with borderline hypertension and remained within the normal range in patients with sustained essential hypertension despite and increase in cardiac mass.
Adult↗
[Regional hemodynamics of the forearm. Comparison between obese and non-obese hypertensive patients].
Forearm hemodynamics using pulsed Doppler flowmetry were studied in 83 men: 15 non-obese and 8 obese normotensive subjects; and 30 non-obese and 30 obese hypertensive patients. Mean ages were similar in the four subgroups. The blood pressure of normotensives and hypertensives was identical in obese and non-obese subjects. Blood flow expressed in ml/mn was significantly higher in obese subjects whether normotensive or hypertensive. However, when blood flow was expressed per unit liter of forearm volume, it was similar in the four subgroups. Forearm vascular resistance, whether expressed as absolute of normalized values, was significantly higher (p less than 0.001) in non-obese hypertensives. When obese and non-obese hypertensives were compared, the former were characterized by higher values of blood velocity and blood flow, and lower values of vascular resistance, whether absolute or normalized values were used. The present study shows that: (i) forearm vascular resistance in hypertensives is increased exclusively in non-obese subjects, and (ii) obese hypertensives, when compared with non-obese hypertensives, are characterized by a hyperkinetic forearm circulation.
Adult↗
[Flow-dependent vasodilation of the brachial artery in the normotensive and essential hypertensive patient].
Brachial artery hemodynamics including brachial artery diameter (D), local blood flow velocity (V) and local volumic blood flow, was studied in 10 normotensive subjects (NT) and 10 age-matched hypertensive patients (HT) (50 +/- 4 vs 43 +/- 4 years; m +/- SEM; NS), using a bidimensional pulsed doppler system at rest (control period), during a 2 (or 4) mn-period of distal circulatory occlusion (DO) and during the following reactive hyperemia (RH). Kinetics of change in blood flow velocity and diameter were determined during successive and reproducible manoeuvres. V and D decreased significantly during DO. During RH (1) V reached similar maximum values in both groups (after 2 mn DO: NT: from 2.4 +/- 1.1 to 19.0 +/- 6.9 cm/s; HT: from 2.9 +/- 0.8 to 17.2 +/- 7.6 cm/s) and (2) D increased significantly in both groups (after 2 mn DO: NT: from 0.395 +/- 0.016 to 0.450 +/- 0.025 cm; p less than 0.001; HT: from 0.408 +/- 0.018 to 0.467 +/- 0.018 cm; p less than 0.001), reaching levels significantly higher than during the control period. The brachial artery vasodilation observed in both groups (NT: +12 +/- 3 p. 100; HT: +15 +/- 3 p. 100 of initial diameter) was significantly greater (p less than 0.001), than the reproducibility of the diameter measurement (3 +/- 1 p. 100). Mean arterial pressure and heart rate dit not change during the whole investigation. Increasing the duration of DO from 2 to 4 mn further enhanced the reactive blood flow velocity but did not change the magnitude of the reactive brachial artery vasodilation.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
[Current treatment regimen in essential arterial hypertension].
The introduction in the treatment of arterial hypertension of angiotensin-converting enzyme inhibitors and calcium inhibitors, as well as the results of extensive multicentric therapeutic trials, suggest that the prescription of antihypertensive drugs will be profoundly altered in the forthcoming years. The "step by step" approach will be abandoned, and each patient will receive one or two drugs chosen for being the most selective and most suitable for his case. These more personalized long-term treatments will be better tolerated, and the greater patient's compliance will make them more effective drugs to the underlying pathology (smoking habits, blood lipid disorders, early arterial lesions) the antihypertensive treatment will have a greater reducing effect on cardiovascular morbidity and mortality.
Antihypertensive Agents↗
Antihypertensive effect of sustained-release isosorbide dinitrate for isolated systolic systemic hypertension in the elderly.
A double-blind, randomized trial was performed in 40 patients, mean age (+/- standard deviation) 80 +/- 4 years, with isolated systolic systemic hypertension to evaluate the antihypertensive effect of oral sustained-release isosorbide dinitrate (ISDN), 20 to 40 mg twice daily, vs placebo. After 12 weeks of treatment, supine systolic blood pressure (BP) decreased from 192 +/- 10 to 162 +/- 12 mm Hg with ISDN (p less than 0.001) and from 189 +/- 10 to 175 +/- 15 mm Hg with placebo (p less than 0.001). On the basis of variance analysis, the decrease in systolic BP was significantly lower with ISDN (27 mm Hg) than with placebo (13 mm Hg). Similar results were observed for supine and erect systolic BP measured at 8 AM and 4 PM, 8 and 12 hours after drug intake. No significant differences in diastolic BP, heart rate or side effects occurred. After the ISDN tapering off-period (2 weeks), systolic BP increased significantly but did not change with placebo. The study provided evidence that in elderly patients with systolic hypertension, sustained-release ISDN induced a selective and sustained decrease in systolic BP, antihypertensive effect was observed 8 and 12 hours after drug administration, and no tolerance phenomenon was noted.
Aged↗