Failure of atrial natriuretic factor to increase with saline load in patients with dilated cardiomyopathy and mild heart failure.

To investigate whether the response of atrial natriuretic factor (ANF) to volume expansion is impaired in the early stages of dilated cardiomyopathy, the effects of saline load (SL; 0.25 ml/kg.min for 120 min) were assessed in 12 patients with dilated cardiomyopathy and asymptomatic to mildly symptomatic heart failure (HF) and in nine normal subjects (N). SL increased plasma ANF levels in N (from 14.3 +/- 2 to 19.5 +/- 3 and 26 +/- 4 pg/ml, at 60 and 120 min, respectively, P less than 0.001), but not in HF (from 42.9 +/- 9 to 45.9 +/- 9 and 43.9 +/- 8 pg/ml). Left ventricular end-diastolic volume (LVEDV) and stroke volume were increased (P less than 0.001) by SL in N but not in HF. Urinary sodium excretion (UNaV) increased in N more than in HF during SL, whereas forearm vascular resistance (FVR) did not change in N and increased in HF (P less than 0.001). In five HF patients SL was performed during ANF infusion (50 ng/kg, 5 ng/kg.min) that increased ANF levels from 37.1 +/- 10 to 146 +/- 22 pg/ml. In this group, SL raised both LVEDV (P less than 0.01) and ANF (P less than 0.05), whereas FVR did not rise. In addition, the UNaV increase and renin and aldosterone suppressions by SL were more marked than those observed in HF under control conditions. Thus, in patients with dilated cardiomyopathy and mild cardiac dysfunction, plasma ANF levels are not increased by volume expansion as observed in N. The lack of ANF response is related to the impaired cardiac adaptations. The absence of an adequate increase of ANF levels may contribute to the abnormal responses of HF patients to saline load.

Reflex control of coronary vascular tone by cardiopulmonary receptors in humans.

To examine whether cardiopulmonary receptors participate in the reflex control of coronary vascular resistance, systemic and coronary hemodynamics were assessed before and during -10 mm Hg lower body negative pressure in eight normal subjects and eight hypertensive patients with left ventricular hypertrophy. In both study groups, lower body negative pressure induced a significant decrease in right atrial pressure, left ventricular filling pressure and cardiac output, an increase in systemic vascular resistance and no change in mean arterial pressure and heart rate. In normal subjects, there was also a significant increase in plasma norepinephrine concentration (from 294 +/- 39 to 421 +/- 47 pg/ml, p less than 0.01). This increase was accompanied by a reduction in coronary blood flow, assessed by the continuous thermodilution method (from 101 +/- 5 to 79 +/- 4 ml/min, p less than 0.05). An increase in coronary vascular resistance (from 0.865 +/- 0.1 to 1.107 +/- 0.1 mm Hg/ml per min, p less than 0.05) and in myocardial oxygen consumption was detected in normal subjects during cardiopulmonary baroreceptor unloading. In contrast, in hypertensive patients, -10 mm Hg lower body negative pressure failed to induce any change in plasma norepinephrine, coronary blood flow or vascular resistance. Intravenous propranolol administration caused no significant change in the systemic hemodynamic response to -10 mm Hg lower body negative pressure in either study group, but it did abolish the decrease in coronary flow and the increase in plasma norepinephrine, coronary vascular resistance and myocardial oxygen consumption observed in normal subjects in control conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Carotid sinus reflex control of coronary blood flow in human subjects.

Systemic and coronary hemodynamics were assessed before and during a reduction in carotid transmural pressure. This reduction was induced by means of a pneumatic neck chamber in 15 normal subjects and 15 hypertensive patients with a normal coronary arteriogram. A reduced baroreflex responsiveness was demonstrated in hypertensive patients as compared with normal subjects by evaluating both the reflex bradycardia evoked by intravenous administration of phenylephrine and the reflex increase in blood pressure during carotid sinus hypotension. In normal subjects, the reduction in carotid transmural pressure induced a significant increase in mean blood pressure, total peripheral resistance, cardiac output, heart rate, coronary vascular resistance, coronary blood flow assessed by the continuous thermodilution method and myocardial oxygen consumption. In hypertensive patients, the same stimulus significantly increased mean blood pressure, cardiac output, heart rate and coronary blood flow while no significant change was detected in coronary vascular resistance and myocardial oxygen consumption. The increase in mean blood pressure, total peripheral resistance and cardiac output was significantly higher in normal subjects than in hypertensive patients. These results suggest that in normal subjects carotid sinus hypotension evokes reflex coronary vasoconstriction, whereas this response is blunted in hypertensive patients with reduced baroreflex sensitivity.

Baroreflex responsiveness in borderline hypertensives: a study with neostigmine.

The baroreflex response to changes in transmural pressure throughout the arterial tree or limited to the carotid sinus was evaluated in ten borderline hypertensives and compared with that observed in ten normal subjects and in ten established hypertensives. Baroreceptor sensitivity was tested by evaluating both heart rate response to phenylephrine-induced increase in arterial pressure and heart rate and blood pressure changes induced by increased neck tissue pressure by means of a neck chamber. The heart rate response to phenylephrine (evaluated by the regression of the R-R interval versus the systolic blood pressure) was depressed both in borderline and established hypertensives as compared with controls. Similarly, the heart rate and the pressor response to increased neck tissue pressure were depressed in both groups of hypertensives. In borderline, but not in established hypertensives, neostigmine administration improved consistently the pressor baroreflex response to increased neck tissue pressure and the heart rate reflex response to both the employed stimuli. These findings indicate that a reduced parasympathetic activity is one of the components involved in the altered baroreflex sensitivity in borderline hypertensives.

Effects of oral salt loading on beta-adrenergic receptor responsiveness in normal and hypertensive subjects.

The effect of oral salt loading (400 mmol per day of NaCl for 7 days) on cardiac and pancreatic beta-receptor responsiveness has been evaluated in 12 patients with established essential hypertension and in seven age-matched control subjects. Cardiac beta-receptor responsiveness was evaluated by assessing the dose of isoprenaline which increased a stable heart rate by 25% (chronotropic dose 25%, CD 25%). Pancreatic beta-receptor responsiveness was measured by the incremental areas of insulin secretion induced by iv infusion of increasing amounts of isoprenaline. Before salt load, CD 25% was significantly higher in hypertensives compared with controls (7.84 +/- 1.34 micrograms vs 3.9 +/- 0.48 micrograms, P less than 0.05) while there was no difference in the isoprenaline-induced insulin secretion between the two groups of subjects. After salt loading, CD 25% was significantly reduced in hypertensive patients but was not modified in normal subjects. Therefore, the difference in CD 25% was no longer detectable between the two groups (5.5 +/- 1.42 micrograms vs 3.2 +/- 0.48 micrograms in normal subjects and in hypertensives, respectively, NS). Furthermore, salt loading failed to induce any change in isoprenaline-induced insulin secretion in either groups. These results support the existence of a relationship between sodium intake and adrenergic beta-receptor responsiveness in human hypertension.

Salt-induced plasticity in cardiopulmonary baroreceptor reflexes in salt-resistant hypertensive patients.

To investigate the effects of salt loading on cardiopulmonary and arterial baroreceptor reflexes, 34 hypertensive patients underwent two 4-day periods with different dietary sodium intakes (70 and 370 meq/day). The patients were classified as salt-sensitive or salt-resistant depending on whether the mean arterial pressure value obtained on day 4 of high salt intake did or did not increase by 8% or more. In 22 patients cardiopulmonary and carotid baroreceptor reflexes were assessed during each dietary period by measuring the reflex responses to the application of -10 mm Hg lower body negative pressure and of +60 mm Hg increase in neck tissue pressure. Salt-resistant patients (n = 16) retained less sodium than salt-sensitive patients (n = 6) and showed a reduction in plasma norepinephrine and forearm vascular resistance during high sodium intake, whereas the salt-sensitive patients did not. During low sodium diet, no significant differences could be detected in the reflex responses to cardiopulmonary and carotid baroreceptor unloading between the two groups. High salt diet, however, potentiated the gain of cardiopulmonary baroreceptor reflex, which was expressed as the increase in plasma norepinephrine or forearm vascular resistance per millimeter of mercury decrease in pulmonary capillary wedge pressure, only in the salt-resistant hypertensive patients. In addition, the atrial natriuretic factor response to changes in pulmonary capillary wedge pressure was significantly enhanced by high salt intake only in the salt-resistant hypertensive patients. The reflex responses to carotid baroreceptor unloading were unaffected by salt loading in either group. In the remaining 12 patients, the hemodynamic effects of graded lower body negative pressure (-5, -10, -15 mm Hg) and neck tissue positive pressure (+30, +45, +60 mm Hg) were tested for both diets. Again, high salt intake significantly potentiated the cardiopulmonary baroreceptor reflex gain, expressed as the slope of the linear correlation between the changes in forearm vascular resistance (mm Hg/ml/min/100 g) and pulmonary capillary wedge pressure (mm Hg), in salt-resistant (from 3.8 +/- 0.9 to 7.2 +/- 1.0, p less than 0.05) but not in salt-sensitive patients (from 4.2 +/- 0.9 to 3.2 +/- 0.6, NS). In conclusion, the present study demonstrates that high salt diet potentiates cardiopulmonary baroreceptor reflexes and enhances atrial natriuretic factor response in salt-resistant but not in salt-sensitive hypertensive patients. The salt-induced plasticity of cardiopulmonary baroreceptor reflexes may exert a protective effect against the development of salt-induced hypertension by augmenting the reflex vasodilatory response to volume expansion.(ABSTRACT TRUNCATED AT 400 WORDS)

Impaired control of vasopressin release in hypertensive subjects with cardiac hypertrophy.

The effects of graded lower body negative pressure (-10 and -40 mm Hg) on vascular resistance and plasma vasopressin, norepinephrine, and renin activity were assessed in seven hypertensive subjects with left ventricular hypertrophy and seven sex-matched and age-matched normotensive subjects. In both groups increasing levels of lower body negative pressure induced a progressive decrease in right atrial pressure and an increase in vascular resistance. In normal subjects plasma vasopressin, norepinephrine, and renin activity were progressively raised, whereas only the higher level of stimulation increased plasma renin activity, norepinephrine, and vasopressin in hypertensive subjects. Propranolol induced a significant increase in plasma vasopressin in normal subjects (from 1.3 +/- 0.1 to 2.0 +/- 0.1 pg/ml; p less than 0.05) but not in hypertensive subjects. In this latter condition -10 mm Hg lower body negative pressure failed to increase plasma vasopressin, norepinephrine, and renin activity in normal subjects. Propranolol abolished the change in plasma renin activity in both groups, reduced the increase in vascular resistance induced by -40 mm Hg lower body negative pressure in normotensive subjects, but did not modify the rise in vasopressin elicited by this stimulus in normal subjects or the humoral and hemodynamic reflex responses evoked in hypertensive subjects. These results suggest that cardiopulmonary receptors are involved in the control of vasopressin release in normal subjects, whereas in hypertensive subjects with left ventricular hypertrophy, this control is altered because of an impaired function of cardiopulmonary receptors.

Studies of the mechanisms underlying impairment of beta-adrenoceptor-mediated effects in human hypertension.

To investigate the impairment of beta-adrenoceptor responsiveness in human hypertension, we evaluated the effect of an oral salt load (400 mEq/day of NaCl for 7 days) on plasma catecholamine concentrations and beta-adrenoceptor-mediated effects in 11 young patients with mild essential hypertension. Responses of heart rate and plasma cAMP to isoproterenol administration were used as indices of beta-adrenoceptor responsiveness. Salt loading induced a significant reduction in the dose of isoproterenol required to raise the heart rate by 25 bpm (CD25) (from 7.6 +/- 1.5 to 5.3 +/- 0.9 micrograms, p less than 0.05) and an increase in the slopes of the regression lines for heart rate changes and isoproterenol doses (delta HR/IS) (from 3.3 +/- 0.6 to 4.7 +/- 0.7, p less than 0.05) and for plasma cyclic AMP (cAMP) level changes and isoproterenol doses (delta cAMP/IS) (from 0.3 +/- 0.06 to 1.4 +/- 0.3, p less than 0.05). After salt loading there was a significant reduction in plasma catecholamine concentrations with a significant relationship between changes in upright plasma epinephrine levels and changes in CD25 (r = 0.904, p less than 0.01) and in the slopes for delta HR/IS (r = 0.983, p less than 0.001) and delta cAMP/IS (r = 0.922, p less than 0.001). These results support the hypothesis that the impairment of beta-adrenoceptor sensitivity observed in human hypertension is associated with a beta-adrenoceptor overstimulation due to chronically elevated adrenergic tone.

Effect of furosemide on plasma concentration and beta-blockade by propranolol.

Although propranolol and furosemide are used together for hypertension, the effects of furosemide on plasma levels and beta-blocking action of propranolol are not known. Ten healthy subjects received propranolol 40 mg orally; the mean plasma propranolol levels in 60, 90, 180, and 300 min were 85 +/- 16, 90 +/- 7, 82 +/- 8, and 58 +/- 8 ng/ml. Propranolol was then given together with furosemide (25 mg orally) and the propranolol blood level was measured. Mean propranolol plasma levels were 106 +/- 11 ng/ml at 60 min, 120 +/- 12 ng/ml at 90 min (p less than 0.01), 102 +/- 8 ng/ml at 180 min (p less than 0.05), and 78 +/- 8 ng/ml at 300 min (p less than 0.01). Six additional subjects were given an infusion of 1 microgram/min isoproterenol increased by 0.5 microgram/min every 2 min until the heart rate rose by 25% after oral administration of furosemide 25 mg. This procedure was repeated after propranolol (40 mg orally) and propranolol with furosemide (25 mg orally). The amount of isoproterenol which raised the heart rate by 25% was 2.6 +/- 0.3 micrograms after furosemide alone and 17.7 +/- 2 micrograms after propranolol (p less than 0.01). After propranolol with furosemide the dose of isoproterenol required to elevate heart rate by 25% was 109 +/- 15 micrograms (p less than 0.001).

Predictability of antihypertensive efficacy of selective beta 1 blockers.

The possibility that hemodynamic and biohumoral factors may help predict the antihypertensive effectiveness of selective beta 1 blockers was investigated. The effects of 3 wk of treatment with two selective beta 1 blockers, metoprolol and atenolol, were observed in 54 patients with mild or moderate essential hypertension. No significant difference between the hemodynamic effects of the two drugs was found. The percent fall in systolic blood pressure induced by the two correlated strongly with the pretreatment values of the chronotropic response to isoproterenol and with the pretreatment values of cardiac output, heart rate, and plasma renin activity (PRA). There was no correlation between the decrease in systolic blood pressure induced and initial 24-hr urinary catecholamine output, total peripheral resistance, and plasma aldosterone. Percent fall in diastolic blood pressure correlated only with the pretreatment levels of PRA. Our results support the view that the hypotensive effect of beta 1 blockers are predictable on the basis of the pretreatment values of chronotropic response to isoproterenol, PRA, heart rate, and cardiac output.

Digitalis restores the forearm sympathetic response to cardiopulmonary receptor unloading in hypertensive patients with left ventricular hypertrophy.

OBJECTIVE: To investigate whether the impaired reflex response to cardiopulmonary baroreceptor unloading in hypertensive patients with left ventricular hypertrophy can be promptly improved by a pharmacological challenge. For this purpose we studied the effects of acute digitalis administration on cardiopulmonary baroreflex, evaluated by forearm noradrenaline spillover. METHODS: Eleven hypertensives with left ventricular hypertrophy and 10 age- and sex-matched normotensives underwent the application of -5 and -10 mmHg lower-body negative pressure (LBNP) before and after the administration of digitalis. Forearm noradrenaline spillover, measured using a tracer technique, was used to estimate the reflex sympathetic response. RESULTS: Under control conditions LBNP evoked a similar fall in right atrial pressure in the two study groups. In the normotensives there was a significant increase in forearm noradrenaline spillover. In the hypertensives no significant changes in forearm noradrenaline spillover were found. Intravenous administration of 0.02 mg/kg lanatoside C was associated with an increase in systolic blood pressure and a reduction in forearm noradrenaline spillover in both groups. In the normotensives the percentage change in forearm noradrenaline spillover induced by LBNP increased significantly in response to digitalis administration. However, digitalis restored the response of forearm noradrenaline spillover to LBNP in the hypertensives, so that no significant difference in this response was detected between the two study groups. Digitalis did not modify the effects of LBNP on cardiac pressures in either group. CONCLUSIONS: The present results demonstrate that administration of lanatoside C restores the response of forearm noradrenaline spillover to cardiopulmonary baroreceptor unloading in hypertensive patients with left ventricular hypertrophy. This indicates that the impairment of cardiopulmonary baroreflexes in these patients can be reversed by acute pharmacological treatment. Therefore, impairment of this reflex response seems to be related to functional rather than to structural abnormalities of the hypertrophied ventricle.

Identification of viable myocardium in patients with chronic coronary artery disease: comparison of thallium-201 scintigraphy with reinjection and technetium-99m-methoxyisobutyl isonitrile.

We compared the results of 201Tl reinjection and those of 99mTc-methoxyisobutyl isonitrile (MIBI) in identifying viable myocardium in 20 male patients with angiographically proven coronary artery disease (CAD) and left ventricular dysfunction (ejection fraction 30% +/- 8%). All patients had irreversible defects on standard exercise-redistribution thallium imaging. Thallium was reinjected immediately after the redistribution study, and images were reacquired. The patients also underwent stress and rest 99mTc-MIBI myocardial scintigraphy (2-day protocol). A total of 300 myocardial regions were analyzed, of which 122 (41%) had irreversible thallium defects on redistribution images before reinjection. Of the 122 myocardial regions with irreversible defects on standard stress-redistribution thallium cardiac imaging, 65 (53%) did not change at reinjection and 57 (47%) demonstrated enhanced uptake of thallium after reinjection. Of the same 122 irreversible defects on stress-redistribution thallium, 100 (82%) appeared as fixed defects and 22 (18%) were reversible on 99mTc-MIBI myocardial scintigraphy. These data indicate that 201Tl cardiac imaging with rest reinjection is superior to 99mTc-MIBI myocardial scintigraphy in identifying viable myocardium in patients with chronic CAD, suggesting that regions with severe reduction of 99mTc-MIBI uptake both on stress and rest images may contain viable myocardium.

Reverse redistribution in resting thallium-201 myocardial scintigraphy in chronic coronary artery disease: an index of myocardial viability.

UNLABELLED: The aim of this study was to evaluate whether segments with reverse redistribution on rest-redistribution 201Tl scintigraphy represent viable tissue or scar. METHODS: Nineteen patients (17 men, 2 women; mean age 53 +/- 8 yr) with coronary artery disease underwent rest-redistribution 201Tl study before coronary revascularization. Regional 201Tl uptake was analyzed quantitatively. Regional left ventricular wall motion was assessed before and after coronary revascularization using two-dimensional echocardiography and a three-point scale (1 = normal, 2 = hypokinetic, 3 = akinetic/dyskinetic). Two patterns of reverse redistribution were identified: pattern with normal 201Tl uptake in rest and abnormal in redistribution images and pattern with abnormal 201Tl uptake in rest and a significant decrease in redistribution images. RESULTS: Of the 247 segments analyzed, 85 were classified as normal, 37 as reversible defects, 83 as fixed defects and 42 as reverse redistribution (19 RR-A, 23 RR-B). Segments with RR-A differed from those with RR-B in wall motion score (1.4 +/- 0.7 versus 2.0 +/- 1.0). Electrocardiographic Q-waves were present in 26% of segments with RR-A and in 57% of segments with pattern B. After revascularization, all dyssynergic segments with pattern A showed improved wall motion, while only 40% of segments with pattern B and abnormal wall motion had such improvement. CONCLUSION: Our results suggest that dyssynergic segments with pattern A should be considered viable, while more caution should be used in classifying those with pattern B.

QT/QS2 ratio as an index of autonomic tone changes.

The effects of changes in sympathetic tone on QT/QS2 ratio were studied in 10 healthy subjects aged 21 to 24 years. The subjects underwent a bicycle ergometer exercise, a tilt test, a decrease in carotid transmural pressure induced by means of pneumatic neck chamber, an i.v. injection of phenylephrine. A phonocardiogram and ECG were simultaneously recorded at a paper speed of 100 mm/s to evaluate QT and QS2 intervals in each test. In basal conditions, the QT/QS2 ratio was less than 1, whereas it increased progressively during the physical exercise and became greater than 1 at peak exercise. Both the upright position and the increase in neck-tissue pressure induced a significant increase in the QT/QS2 ratio as compared with the basal values, whereas i.v. administration of phenylephrine reduced significantly the QT/QS2 ratio. These results demonstrate that those stimuli which induce a rise in adrenergic activity may increase the QT/QS2 ratio. In contrast, the reflex inhibition of the adrenergic activity induced by phenylephrine is accompanied by a reduction in QT/QS2 ratio. Therefore, the QT/QS2 ratio might represent a reliable index of sympathetic cardiac tone.

Effect of acebutolol on left ventricular hemodynamics and anatomy in systemic hypertension.

In 18 patients with mild or moderate essential hypertension who responded favorably to acebutolol antihypertensive therapy, echocardiography (echo) was performed in the basal condition and after 6 and 12 months of follow-up. Acebutolol induced a significant decrease in blood pressure (BP), from a basal value of 167 +/- 3/105 +/- 2 mm Hg to 138 +/- 5/90 +/- 2 mm Hg after 6 months (p less than 0.01) and to 134 +/- 3/91 +/- 3 mm Hg after 1 year (p less than 0.01), and in heart rate, from 75 +/- 3 to 63 +/- 2 beats/min after 6 months (p less than 0.01) and to 63 +/- 2 beats/min after 1 year (p less than 0.01). The decrease in BP was achieved through a decrease in cardiac output from 6.3 +/- 0.28 to 5.3 +/- 0.25 liters/min after 6 months (p less than 0.05) and to 5.32 +/- 0.2 liters/min after 1 year (p less than 0.05), which resulted from a reduction in heart rate; stroke volume did not show significant change during the treatment and left ventricular (LV) performance was improved. There was a parallel decrease in LV posterior wall and ventricular septal thicknesses and estimated LV mass. In patients with LV hypertrophy, the change in mass was significantly correlated with the change in heart rate both after 6 and 12 months of therapy (r = 0.6234, p less than 0.05 and r = 0.7121, p less than 0.05 after 6 and 12 months, respectively).

Effects of intravenous verapamil administration on left ventricular diastolic function in systemic hypertension.

The effects of intravenous verapamil administration (0.1 mg/kg as a bolus followed by an infusion of 0.007 mg/kg/min) were studied using high-temporal-resolution radionuclide angiography in 27 patients with hypertension. Verapamil administration increased heart rate from 69 +/- 11 to 75 +/- 12 beats/min (p less than 0.001) and decreased systolic, diastolic and mean blood pressures (BPs) from 155 +/- 21/102 +/- 12 mm Hg (mean 119 +/- 14) to 142 +/- 19/95 +/- 12 mm Hg (mean 109 +/- 13) (p less than 0.001 for all). Ejection fraction decreased significantly (from 65 +/- 10% to 60 +/- 11%, p less than 0.005); peak filling rate, however, increased significantly only in patients in whom it was subnormal in the basal study (from 2.2 +/- 0.4 to 3.0 +/- 0.6 end-diastolic counts/s, p less than 0.001). These latter patients had significantly higher values of left ventricular (LV) mass index than patients with normal or increased peak filling rate (129 +/- 22 vs 112 +/- 22 g/m2, respectively, p less than 0.05). The isovolumic relaxation period changes were inversely related to the baseline values (r = 0.83, p less than 0.001). In the subgroup of patients in whom isovolumic relaxation period lengthened, time to end systole decreased (from 360 +/- 31 to 329 +/- 30 ms, p less than 0.025) and time to onset of rapid filling increased (from 420 +/- 31 to 451 +/- 34 ms, p less than 0.025), whereas these 2 intervals had opposite patterns in patients in whom isovolumic relaxation period decreased or did not change.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac function in systemic hypertension before and after reversal of left ventricular hypertrophy.

In 3 age- and sex-matched groups of subjects--15 normotensives, 15 hypertensives without left ventricular (LV) hypertrophy and 15 hypertensives with LV hypertrophy--the slopes of the regression line obtained by plotting the individual values of LV fractional shortening against the corresponding values of echocardiographic end-systolic stress were compared. The first 2 groups were studied only in control conditions while the third group was restudied after a 20% reduction in LV mass index induced by a long-term antihypertensive treatment and after a 3-week washout period. A significant relation between fractional shortening and end-systolic stress was found in all instances. The slope of this correlation was higher in normotensives (-0.251) and in hypertensives without LV hypertrophy (-0.232) (both p less than 0.01) than in hypertensives with ventricular hypertrophy (-0.079). In this latter group, the slope increased after the reversal of LV hypertrophy (-0.230, p less than 0.01) and remained unchanged (-0.202) at the end of the washout period. No difference was detectable between the slopes obtained in these patients after reversal of LV hypertrophy, both with the antihypertensive treatment on and off, and those of normotensives and hypertensives without LV hypertrophy. Thus, LV hypertrophy attenuates the influence of changes in afterload on LV function. Reversal of LV hypertrophy restores a fractional shortening end-systolic stress relation quite comparable to that found both in normotensives and in hypertensives before the development of LV hypertrophy.

Improvement of diastolic function after reversal of left ventricular hypertrophy induced by long-term antihypertensive treatment with tertatolol.

In 15 previously untreated hypertensive subjects with left ventricular (LV) hypertrophy who responded favorably (supine blood pressure less than or equal to 140/90 mm Hg) to antihypertensive treatment with a nonselective beta-blocking agent, tertatolol, the effects of reversal of LV hypertrophy on systolic and diastolic function were assessed. Patients underwent echocardiographic and radionuclide studies in control conditions (phase 1), after 1 month of blood pressure normalization (phase 2), after reversal of LV hypertrophy or at least a 20% reduction of LV mass compared to basal value (phase 3) and finally, after a 1-month washout (phase 4). In phase 2, blood pressure (130 +/- 2/85 +/- 1 vs 148 +/- 4/104 +/- 1 mm Hg) and heart rate (59 +/- 1 vs 76 +/- 2 beats/min) decreased (both p less than 0.01); LV mass remained unchanged. There were improvements in peak filling rate (end-diastolic volume/s) (2.4 +/- 0.1 vs 2.0 +/- 0.1), ejection fraction (65 +/- 1 vs 61 +/- 1%) and their ratio (stroke counts/s) (3.7 +/- 0.2 vs 3.2 +/- 0.1) (all p less than 0.05). In phase 3, blood pressure and heart rate were unchanged and reversal of LV hypertrophy was accompanied by a further increase in peak filling rate (2.9 +/- 0.1), ejection fraction (69 +/- 1%) and their ratio (4.1 +/- 0.1) compared to phase 2 (all p less than 0.01). Finally, in phase 4 blood pressure and heart rate returned to the basal value, but peak filling rate (2.7 +/- 0.1) and ejection fraction (65 +/- 1%), although reduced compared to phase 3, were still higher than phase 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Reversal of cardiac and large artery structural abnormalities induced by long-term antihypertensive treatment with trandolapril.

In 15 patients with untreated mild to moderate essential hypertension and left ventricular hypertrophy, we assessed blood pressure, echocardiographic left ventricular mass index, brachial artery compliance (pulsed doppler flowmetry), and calculated forearm vascular resistance (strain gauge plethysmography) before, during (6 and 12 months) and after (1 month washout period) 1 year of satisfactory (blood pressure < or = 140/90 mm Hg) antihypertensive therapy with the angiotensin-converting enzyme inhibitor trandolapril (2.0 mg orally once daily). During the antihypertensive effective treatment, we observed a significant reduction of systolic and diastolic blood pressures, left ventricular mass index, and forearm vascular resistance at both 6 and 12 months. In addition, brachial artery compliance was significantly increased. After washout, systolic (156 +/- 3 mm Hg) and diastolic (102 +/- 1 mm Hg) blood pressures returned to levels comparable to baseline. However, left ventricular mass index (132 +/- 4; p < 0.01) and brachial artery compliance (1.53 +/- 0.01; p < 0.01) were still different from baseline. These results demonstrate that chronic antihypertensive treatment with trandolapril is associated with a stable regression of cardiac and vascular abnormalities, which is partially unrelated to the blood pressure lowering effect.

Role of prostaglandins in the renal handling of a salt load in essential hypertension.

Renal function and systemic hemodynamics were assessed in 10 hypertensive patients and in 10 age-matched normotensive subjects during control conditions (80 mEq of sodium/day) and after a salt load, either alone (480 mEq/day) or combined with indomethacin or sulindac. Indomethacin was used to induce ubiquitous inhibition of prostaglandin synthesis and sulindac to inhibit prostaglandin synthesis in all tissues except the kidney. Under control conditions there was no significant difference between the 2 groups in any measurement except blood pressure and total peripheral resistance. Also, the changes induced by salt load in the 2 groups were comparable. However, after indomethacin administration, only hypertensive patients showed a significant reduction in the 24-hour sodium excretion (from 417 +/- 61 to 317 +/- 49 mEq, p less than 0.05), so that the difference between this value and the corresponding value of normotensive subjects (453 +/- 79 mEq) became significant (p less than 0.05). The changes in sodium excretion in hypertensive patients were significantly correlated with the changes in renal plasma flow (r = 0.803, p less than 0.01). However, cardiac output and renal blood flow showed a similar pattern in normal and hypertensive persons. Finally, after the addition of sulindac to salt load, the differences in the 24-hour sodium excretion vanished. These results were also confirmed in an ancillary study performed, using the same protocol, in 10 other hypertensive patients using ibuprofen rather than indomethacin. Our data suggest that renal prostaglandins participate in renal disposal of chronic salt load in hypertensive patients but not in normal persons.