Effects of once-daily angiotensin-converting enzyme inhibition and calcium channel blockade-based antihypertensive treatment regimens on left ventricular hypertrophy and diastolic filling in hypertension: the prospective randomized enalapril study evaluating regression of ventricular enlargement (preserve) trial.

BACKGROUND: The Prospective Randomized Enalapril Study Evaluating Regression of Ventricular Enlargement (PRESERVE) study was designed to test whether enalapril achieves greater left ventricular (LV) mass reduction than does a nifedipine gastrointestinal treatment system by a prognostically meaningful degree on a population basis (10 g/m(2)). METHODS AND RESULTS: An ethnically diverse population of 303 men and women with essential hypertension and increased LV mass at screening echocardiography were enrolled at clinical centers on 4 continents and studied by echocardiography at baseline and after 6- and 12-month randomized therapy. Clinical examination and blinded echocardiogram readings 48 weeks after study entry in an intention-to-treat analysis of 113 enalapril-treated and 122 nifedipine-treated patients revealed similar reductions in systolic/diastolic pressure (-22/12 versus -21/13 mm Hg) and LV mass index (-15 versus -17g/m(2), both P>0.20). No significant between-treatment difference was detected in population subsets defined by monotherapy treatment, sex, age, race, or severity of baseline hypertrophy. Similarly, there was no between-treatment difference in change in velocities of early diastolic or atrial phase transmitral blood flow. More enalapril-treated than nifedipine-treated patients required supplemental treatment with hydrochlorothiazide (59% versus 34%, P<0.001) but not atenolol (27% versus 22%, NS). CONCLUSIONS: Once-daily antihypertensive treatment with enalapril or long-acting nifedipine, plus adjunctive hydrochlorothiazide and atenolol when needed to control blood pressure, both had moderately beneficial and statistically indistinguishable effects on regression of LV hypertrophy.

[Silent myocardial ischemia in patients with essential hypertension]. / "Nemaia" ishemiia u bol'nykh gipertonicheskoi bolezn'iu.

Holter monitoring was performed in 61 patients with essential hypertension. Painless, silent ST segment depression was found in 34 patients. Exercise myocardial scintigraphy indicated the occurrence of transient perfusion defects without abnormal clearance (Group 1) and those with abnormal clearance (Group 2). The patients from Group 1 showed more severe myocardial hypertrophy, higher platelet aggregation, coronary atherosclerosis was detected in 1 case. The patients from Group 2 exhibited less myocardial hypertrophy, lower platelet aggregation. Coronary atherosclerosis was revealed in 4 cases. The patients from the two groups had elevated plasma norepinephrine levels at the onset of silent myocardial ischemia.

["Silent" myocardial ischemia and the activity of the sympathetic-adrenal system in hypertension patients]. / "Nemaia" ishemiia miokarda i aktivnost' simpatiko-adrenalovoi sistemy u bol'nykh gipertonicheskoi bolezn'iu.

The aim of the study was to assess the sympathoadrenal activity at the time of silent ischemia event in hypertensive patients. In 15 hospitalized hypertensive patients having silent ischemia event during Holter ECG monitoring while walking, blood samples for catecholamines were taken at the time of silent ischemia event, pointed with alarm by the real time ECG "Q Med" monitor (USA). Control blood samples were taken under the same conditions without ST-segment depression. Plasma noradrenaline (NA) during silent ischemia was significantly higher than the control level without ischemia (458 +/- 71 ng/l vs 717 +/- 95 ng/l) (p less than 0.01). The changes in plasma NA correlated with left ventricular mass assessed by echocardiography (r = 0.70, p less than 0.01). The role of sympathoadrenal hyperactivity in the genesis of silent myocardial ischemia in patients with essential hypertension is discussed.

Hypertension precursors in inner city minority females.

Screening for precursors and objective evidence for hypertension was done in an inner city family planning clinic. Prior history of high blood pressure occurred in 4 of 41 young black females (10%) and pressures greater than 124/80 mmHg occurred in 2 of 41 (5%). A family history of heart disease occurred in 7 of 41 (17%), of high blood pressure in first degree relatives in 17 of 29 (60%), of death due to high blood pressure in 12 of 41 (29%). Family history may be more predictive of future events than objective data in this age/sex cohort.

Influence of norepinephrine administration upon pituitary hormone secretion in normal men.

This study has investigated the effects of 6.2, 12.5, 25, 50 and 100 ng/kg/min/60 min of NE infused to normal men. Blood samples were obtained every 10 min, before, during and after drug administration for 3 consecutive h. Plasma levels on NE, LH, FSH, PRL, and GH were measured in all samples. The administration of 12.5 ng/kg/min over 60 min of NE induced a significant increase (p less than 0.001) in plasma NE levels (n = 5) from a mean (+/- SE) baseline of 239 +/- 14 ng/L to 706 +/- 54 ng/L which peaked and plateaued at 40 min. The calculated area under the curve was 18562 +/- 3537 ng/L/h of NE and significantly higher (p less than 0.001) than during the h before the infusion (2358 +/- 780 ng/L/h). This increase in plasma NE correlated well with the rise in plasma LH which showed a steady increase from baseline of 7.4 +/- 1.3 mIU/ml to a significant (p less than 0.05) peak of 11 +/- 1.9 mIU/ml at the end of the infusion. Furthermore, analysis of the area under the curve revealed a greater (p less than 0.05) LH release during the NE infusion (180 +/- 18 mIU/ml/h) than before the infusion (92 +/- 17 mIU/ml/h). With the exception of the studies utilizing 12.5 ng/kg/min/60 min, all other doses of NE resulted in no significant and/or consistent changes in plasma concentration of LH, FSH, GH and PRL. Thus, the direct participation of NE in the control of LH secretion in humans seems to occur in a very narrow window.

Effects of clonidine on central and peripheral nerve tone in primary hypertension.

To define the mechanisms whereby clonidine lowers blood pressure, we measured cerebrospinal fluid and plasma levels of norepinephrine, normetanephrine, epinephrine, dopamine, and the dopamine metabolite homovanillic acid in 10 primary hypertensive subjects before and after 3 months of clonidine treatment (mean dose, 0.68 mg/day). Catecholamines were measured by radioenzymatic methods. Cerebrospinal fluid and plasma sampling was performed after subjects had fasted and remained supine overnight, and plasma sampling was repeated 2 hours later, after subjects had ambulated. Supine and upright blood pressure fell, as might be expected. Cerebrospinal fluid levels of norepinephrine and normetanephrine fell significantly, but dopamine and homovanillic acid levels were unchanged. Plasma norepinephrine, normetanephrine, and epinephrine levels decreased 30 to 50%, and supine dopamine levels also fell. The percent fall in supine blood pressure was related to the fall of cerebrospinal fluid and plasma norepinephrine. There were also positive relationships between the decreases of plasma norepinephrine and of normetanephrine and dopamine. The cerebrospinal fluid/plasma norepinephrine ratio was unaffected by clonidine, suggesting that the drug lowered both pools equally. Our findings indicate that clonidine decreases both central and peripheral norepinephrine activity. The dopaminergic activity of cerebrospinal fluid was unaffected by clonidine, and though plasma dopamine levels tended to be lower after treatment, mean plasma prolactin level, an index of dopaminergic activity, was also unchanged. The fall in plasma epinephrine level is probably related to diminished sympathetic adrenomedullary stimulation and is unlikely to contribute to clonidine's antihypertensive action. These results also suggest that measurement of normetanephrine in cerebrospinal fluid and plasma provides a good index of norepinephrine activity.

[Reactivity of the cardiovascular system and of the pressor neurohumoral systems in hypertension patients]. / Reaktivnost' serdechno-sosudistoi sistemy i nekotorykh pressornykh neirogumoral'nykh sistem u bol'nykh gipertonicheskoi bolezn'iu.

Correlations between sympathoadrenal, renin-angiotensin and cardiovascular (BP and heart rate) response to psychoemotional and physical stress and antebrachial skin vascular response to noradrenaline were examined in patients with essential hypertension. Four groups of patients were identified on the basis of the magnitude of variation in the examined parameters. The progress of the disease over the past two years was assessed in all patients. The prognosis was particularly unfavorable in the "hyperreactive" group which showed a set of distinctive features: increased vascular response to noradrenaline, a greater BP rise in response to stress, greater sympathoadrenal activation, increased neuroticism, as well as significantly older age of the patients and greater severity and duration of the disease. No intergroup differences in plasma renin activity could be demonstrated. Possible use of vascular response to noradrenaline, and BP and plasma catecholamine variation in response to psychoemotional stress as criteria for the assessment of the severity and outcome of essential hypertension is discussed.

Comparison of metabolic and clinical effects of four oral contraceptive formulations and a contraceptive vaginal ring.

A group of 100 women desiring OC received one of the following four formulations on a randomized basis: (1) mestranol 50 micrograms and norethindrone 1 mg, , (2) ethinyl estradiol 50 micrograms and norethindrone 1 mg, (3) ethinyl estradiol 35 micrograms and norethindrone 1 mg, and (4) ethinyl estradiol 30 micrograms and levonorgestrel 150 mg. An additional 10 women received a CVR containing levonorgestrel and estradiol. Measurement of a large number of serum chemistries, lipids, proteins, clotting factors, and liver enzymes was obtained before and 3 and 6 months after starting medication. Clinical factors such as weight, blood pressure, bleeding or spotting, or any adverse side effects were also recorded. There was no significant difference in the metabolic parameters measured among the four oral contraceptives except the increase in angiotensinogen was slightly less in the groups receiving the compounds with 30 or 35 micrograms estrogen and the groups receiving the norgestrel compound had no increase in triglycerides and a slight decrease in cholesterol levels. When the CVR was compared with all oral contraceptives it was found to produce no change in angiotensinogen levels and a decrease in triglycerides. Some of each group of OC users had a lowering of antithrombin III to abnormal levels but none of the CVR users had his amount of decrease. As oral steroids with 30 or 35 micrograms of estrogen do not produce significantly less metabolic alteration than do compounds with 50 micrograms of estrogen, it is unlikely that their use will reduce the incidence of the uncommon serious adverse effects associated with OC use. However, since the CVR's did not increase angiotensinogen, their use as contraceptives will most likely not produce hypertension and possibly the other serious circulatory problems which are increased in some OC users.

PIP: 4 oral contraceptive (OC) formulations were randomly assigned to a group of 100 women and metabolic effects (hepatic enzymes, lipid, renin, immunoglobulin proteins, and blood coagulation factors) were studied; in addition, 10 other women wore a contraceptive vaginal ring (CVR) which contained levonorgestrel and estradiol. The 4 formulations were: 1) mestranol 50 mcg + norethindrone 1 mg; 2) ethinyl estradiol 50 mcg + norethindrone 1 mg; 3) ethinyl estradiol 35 mcg + norethindrone 1 mg; and 4) ethinyl estradiol 30 mcg + levonorgestrel 150 mg. Clinical features of use of CVRs and OCs were also studied (body weight, blood pressure, and menstruation disorders). Metabolic parameters showed no significant differences among the 4 OC formulation users except that angiotensinogen increased to a lesser extent in groups receiving 30 or 35 mcg of estrogen; groups administered the norgestrel compound saw no increase in triglycerides, and a slight decrease in cholesterol levels. Comparison of CVR with OCs showed no change in angiotensinogen levels but a decrease in triglycerides was noted. Some of each group of OC users had a lowering of antithrombin III to abnormal levels but none of the CVR users had a similar decrease. CVRs seem indicated in persons with serious circulatory problems because they did not affect blood pressure and other circulatory parameters occasionally affected by OC use. 5 tables present the precise data measured for all parameters. A brief discussion follows the study's presentation.

Increased catecholamine excretion after labetalol therapy: a spurious effect of drug metabolites.

Patients with essential hypertension were treated for four weeks with the alpha- and beta-adreno-receptor blocking agent labetalol. Urinary excretion of total catecholamines, metanephrine plus normetanephrine and vanillylmandelic acid was measured with various methods before and during treatment. An unidentified substance interfering with the fluorimetric method for catecholamines and the photometric assay for metanephrines caused falsely high values of those substances. Using appropriate methodology no changes of total catecholamines, metanephrine plus normetanephrine and vanillylmandelic acid excretion were found after labetalol therapy. Our findings are important in preventing errors in the diagnosis of pheochromocytoma as well as in the evaluation of the effects of labetalol on the sympathetic nervous system in man.

Raised cerebrospinal fluid norepinephrine in some patients with primary hypertension.

To test whether central neurogenic factors participate in blood pressure elevation in primary hypertension, we studied the concentrations of: norepinephrine, epinephrine and dopamine-beta-hydroxylase (DBH) in cerebrospinal fluid (CSF); and norepinephrine, epinephrine, DBH and plasma renin activity (PRA) in plasma of 22 subjects (seven with primary hypertension, 11 normotensive patients with non-systemic neurological disorders, and four with secondary hypertension). Plasma and CSF norepinephrine (NE) were increased in primary hypertensives compared to normotensives. Cerebrospinal fluid norepinephrine was related to diastolic blood pressure, and systolic blood pressure when normotensive and primary hypertensives were taken together. The CSF norepinephrine of primary hypertensive patients was correlated with natural log PRA. The CSF norepinephrine was correlated inversely with age in primary hypertensive patients but not in the normotensive subjects. The low CSF norepinephrine and epinephrine, despite markedly increased plasma NE and epinephrine, in two patients with pheochromocytoma, indicate a blood-brain barrier for these neurohormones. The observations support the view that the central sympathetic nervous system is involved in the pathogenesis of primary hypertension, particularly in younger patients.