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Omapatrilat, a vasopeptidase inhibitor, simultaneously inhibits neutral endopeptidase and ACE. The efficacy and hormonal profile of omapatrilat and lisinopril were compared in salt-sensitive hypertensive patients. On enrollment, antihypertensive medications were withdrawn, and patients received a single-blind placebo. On day 15, salt-sensitivity determinations were made. Salt-sensitive hypertensive patients returned within 5 to 10 days for baseline evaluations of ambulatory diastolic blood pressure, ambulatory systolic blood pressure, and atrial natriuretic peptide. Salt-sensitive hypertensive patients were randomized to receive double-blind omapatrilat (n=28) or lisinopril (n=33) at initial doses of 10 mg for 1 week, increasing to 40 and 20 mg, respectively, for an additional 3 weeks. Ambulatory blood pressure and urinary atrial natriuretic peptide were assessed at study termination. Both omapatrilat and lisinopril significantly reduced mean 24-hour ambulatory diastolic and systolic blood pressures; however, omapatrilat produced significantly greater reductions in mean 24-hour ambulatory diastolic blood pressure (P=0.008), ambulatory systolic blood pressure (P=0.004), and ambulatory mean arterial pressure (P=0.005) compared with values from lisinopril. Both drugs potently inhibited ACE over 24 hours. Omapatrilat significantly (P<0.001) increased urinary excretion of atrial natriuretic peptide over 0- to 24-hour (3.8-fold) and 12- to 24-hour (2-fold) intervals; lisinopril produced no change. Omapatrilat significantly (P<0.001) increased urinary excretion of cGMP over the 0- to 24- and 4- to 8-hour intervals compared with that from lisinopril. Neither drug had a diuretic, natriuretic, or kaliuretic effect. In conclusion, in salt-sensitive hypertensive patients, omapatrilat demonstrated the hormonal profile of a vasopeptidase inhibitor and lowered ambulatory diastolic and systolic blood pressures more than lisinopril.

Calcium channel blockers have come into worldwide use for treating hypertension and other circulatory disorders. In recent years, results of several observational studies have suggested that these drugs may not be as safe or effective as other available therapies, such as diuretics and beta-blockers, in the prevention of cardiovascular events. The Nordic Diltiazem (NORDIL) and the International Nifedipine GITS Study: Intervention as a Goal in Hypertension Treatment (INSIGHT) studies were the first two randomized interventional trials in hypertensive patients that directly compared the effects of therapy based on calcium antagonists with those of diuretic and beta-blocker-based treatment on major cardiovascular endpoints. Both studies found that the effectiveness of calcium antagonist therapy was similar to that of diuretic and beta-blocker therapy for preventing the composite primary endpoint of fatal and nonfatal stroke, myocardial infarction, and other cardiovascular death. The two studies shared several nonsignificant trends for cause-specific events, including greater stroke prevention and lesser coronary event prevention in the calcium antagonist groups compared with the diuretic and beta-blocker groups. There is not yet sufficient evidence to prove whether cause-specific differences exist. Results of the NORDIL and INSIGHT studies support incorporating calcium antagonist-based therapy as an additional safe and effective approach for preventing blood pressure-related illness and death.

Background: Hypertension is the most common medical disorder associated with obesity. The relationship between dietary weight loss and the reduction of blood pressure is well established. However, the effect of gastric bypass surgery on blood pressure has not been well studied., Methods: We evaluated the relationship between weight loss and blood pressure in patients with diastolic hypertension who had gastric bypass surgery for morbid obesity. Patients were defined as hypertensive if taking antihypertensive medication or if both the preoperative office and mean hospital diastolic blood pressures were greater than 90 mmHg. Two of the authors (J.L.C., M.E.R.), blinded to all postoperative weights, classified the follow-up hypertensive status into one of four categories: resolved, improved, no change, or worse. The relationship between postoperative changes in blood pressure status and mean weight loss, percent excess weight loss, and body mass index were examined using a one-way analysis of variance. The relationship between postoperative weight loss and blood pressure was assessed in the baseline normotensive population using linear regression analysis., Results: There were 45 patients with diastolic hypertension; 91% were taking an antihypertensive medication. The mean follow-up was 39 months. The mean preoperative weight was 137 kg and the mean weight loss at 1, 12, and 24 months following surgery was 13, 21, and 45 kg, respectively. Twelve months after surgery, hypertension had resolved in 22 patients (54%) and had improved in six patients (15%). These findings persisted through 48 months postoperatively. There was a significant relationship between the percentage of excess weight lost and improvement of hypertension at the 6-month and 12-month follow-up visits. There was also a significant relationship between the body mass index and improvement of hypertension at the 1-month, 12-month, 24-month, and 48-month follow-up visits. In the baseline normotensive patients there was not a significant relationship between our weight loss measures and changes in blood pressure., Conclusions: We conclude that postoperative weight loss in patients undergoing gastric bypass surgery was associated with resolution or improvement of diastolic hypertension in approximately 70% of cases. Resolution or improvement of hypertension occurred more often in patients with a lower postoperative body mass index.

Study Objective: To compare the clinical safety and efficacy of ramipril, a new long-acting nonsulfhydryl inhibitor of angiotensin-converting enzyme (ACE), with enalapril., Design: A randomized, double-blind trial., Setting: Multicenter trial involving 4 large teaching hospitals and 12 community medical centers., Patients: One hundred fifty-nine patients with mild to moderate essential hypertension were enrolled. Two patients were excluded from the efficacy analysis because they failed to return for follow-up., Interventions: Patients were randomized to receive ramipril 2.5, 5, or 10 mg, or enalapril 5, 10, or 20 mg once/day for 3 or 4 weeks., Measurements and Main Results: At baseline, supine diastolic blood pressures ranged from 98-116 mm Hg. Supine and standing systolic blood pressures were reduced by 11.8 and 10.2 mm Hg with ramipril 10 mg (p < or = 0.001) and 9.3 and 10.7 mm Hg with enalapril 20 mg (p < or = 0.001). At the end of the 4-week trial, patients in all six dosage groups had clinically and statistically significant reductions in supine diastolic blood pressure compared with baseline values. The agents did not differ significantly with respect to their blood pressure-lowering effects. Both lowered plasma ACE activity; after 4 weeks, changes from baseline were highly significant for all dosage groups (p < or = 0.001)., Conclusion: Ramipril was as effective in reducing blood pressure and was as well tolerated as enalapril. A larger average decrease in plasma ACE activity was achieved with ramipril over all dosages (71%) compared with that for enalapril (48%), suggesting that ramipril has greater ACE inhibition in the circulation.

In a crossover study, 12 patients with mild to moderate hypertension were given placebo, captopril (12.5 to 50 mg three times a day), and nadolol (20 to 160 mg once a day) to control the resting diastolic blood pressure to a nearly identical degree (p less than 0.0001) (106.1 +/- 4 placebo, 89.6 +/- 8 captopril, 89.8 +/- 7 nadolol). Both drugs lowered (p less than 0.0004) systolic and diastolic blood pressure at rest and during exercise. However, systolic blood pressure lowering during exercise was more pronounced (p less than 0.05) with nadolol than with captopril (difference of 6 mmHg, 16 mmHg, and 21 mmHg at 5.0, 7.0, and 9.0 metabolic equivalents (METS) respectively). Heart rate was lower (p less than 0.05) at rest and during exercise with nadolol as compared with placebo and with captopril. These data imply different mechanisms of action of the two drugs at rest and during exercise and may help in selection of drug therapy in special patient subsets.

Clinic/office (casual), home (self), and twenty-four-hour ambulatory (ABP) blood pressure determinations were compared in 32 subjects defined by conventional office criteria as mild or borderline hypertensives. Office diastolic blood pressures (mean 93.1 +/- 5.3 mmHg) were significantly higher than either home (mean 88.9 +/- 7.1 mm Hg) or awake ABP (mean 88.4 +/- 8.4 mm Hg) readings for the total group, as well as for the mild hypertension subgroup (office mean 96.0 +/- 3.5 mm Hg, home mean 91.0 +/- 8.0, awake ABP mean 90.4 +/- 8.8) but not for the borderline subgroup. In the total study group, office diastolic blood pressure (DBP) correlated better with home DBP (r = 0.58, p = 0.0005), than with the awake ABP (r = 0.40, p = 0.02). Home DBP correlated well with awake DBP (r = 0.48, p = 0.006). In subgroup analysis, office DBPs correlated well with home (self) readings for both the mild (r = 0.53, p = 0.03) and the borderline (r = 0.62, p = 0.01) subgroups. When office DBPs were compared with awake ABP DBPs, the correlation coefficient for the mild subgroup was significant (r = 0.49, p = 0.04); this was not the case for the borderline subgroup (r = 0.10, p = NS). Comparison of home (self) DBPs with awake ABP determinations revealed a good correlation for the borderline subgroup (r = 0.63, p = 0.01) but not for the mild subgroup (r = 0.35, p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Enzymatically inactive renin (IR) is the predominant circulating form of renin. Sympathetic activity may influence plasma renin activity (PRA) by regulation of the conversion of IR to active renin (AR, PRA). It has been demonstrated previously that beta blockade lowers PRA at least partly through inhibition of this conversion process. The authors hypothesized that beta blockade and intrinsic sympathomimetic activity (ISA) would have opposing effects on production of AR from its inactive precursor. Eighteen primary hypertensives (12 male, 6 female, mean age 57.7 +/- 2.7) were entered in a placebo-controlled, double-blind crossover study of the effects of equipotent doses of pindolol and propranolol on mean +/- SEM systolic BP, diastolic BP, heart rate, active renin (AR), total renin (TR), inactive renin (IR), and % AR/TR. Drug dose was titrated to achieve a goal DBP of 90 mmHg or less. Active renin was defined as the rate of generation of angiotensin I in 37 degrees C plasma at pH 5.7. Total renin was determined by preincubation of plasma aliquots with 1.5 mg/mL trypsin in the presence of 5 mM benzamadine for one hour at -4 degrees C prior to assay of renin activity. Inactive renin was calculated as TR minus AR. The BP responses achieve by dose titration of propranolol and pindolol were virtually identical at rest, indicating equivalent depressor effects of the two beta blockers. Heart rate and active renin were, however, lowered to a much greater extent with propranolol as compared with pindolol. The lack of significant pindolol-induced fall in % AR/TR suggests that this drug has little net effect on the formation of AR from IR.(ABSTRACT TRUNCATED AT 250 WORDS)

Eighty-one untreated elderly patients with clinic-defined isolated systolic hypertension (ISH) and 39 normotensive elderly subjects underwent 24-h ambulatory blood pressure monitoring. Before the ambulatory blood pressure monitoring, EDTA-anticoagulated venous blood was obtained from seated subjects for determination of plasma renin activity. Ambulatory blood pressure and heart rates were determined at 15-30-min intervals by a validated, portable non-invasive technique (Spacelabs 5200). Ambulatory blood pressure variability was defined for each subject as the standard deviation and the coefficient of variation of the ambulatory blood pressure. The mean awake systolic blood pressure was much lower than the clinic-determined value in the ISH group (P less than 0.001), but only slightly so in the normotensive group. Forty-two per cent of the clinic-defined ISH group had mean awake ambulatory systolic blood pressures below the 90th percentile of the normotensive group. A discrepancy between office and ambulatory blood pressures was not associated with blood pressure variability, heart rate or plasma renin activity.

Franz Alexander (1939) offered the hypothesis a number of years ago that hypertension can result from the inhibition of feelings of anger. Although a great deal of research has been done to test this hypothesis, the results remain equivocal. Part of the difficulty is that usually only anger was examined, making it impossible to determine the extent to which the results were specific to anger and not general for other negative emotions. A second prevalent problem has been the failure to match hypertensive and control groups on demographic variables that may be relevant to the relationship of hypertension to anger and its expression, such as education, economic level, and age. A third problem is that most studies have investigated only male hypertensives, thereby limiting the generality of the findings. The present study compares male and female hypertensives with carefully matched controls on measures of anxiety, depression, and anger and its suppression.