The effect of fish oil on hypertension, plasma lipids and hemostasis in hypertensive, obese, dyslipidemic patients with and without diabetes mellitus.

We have recently reported that dietary fish oil supplementation (n-3) polyunsaturated fatty acid (PUFA) led to a reduction in blood pressure (BP) and serum triglycerides (TG), in addition to the normalization of the hypercoagulable state in subjects with obesity, hypertension and dyslipidemia without diabetes mellitus (OHD-DM). The aim of the present study was to explore the mechanism of this amelioration by comparing the previous results to those obtained from 19 subjects who, in addition to the conditions described above, also suffer from diabetes mellitus (OHD+DM) and proteinuria. In both the non-diabetic and diabetic groups, a similar reduction was observed in BP (from 158.7/80.8 to 146/72.9 mmHg, and from 157.6/83.2 to 141.9/75.6 mmHg, respectively, P<0.001) and TG levels (from 159.2 to 108.0 mg/dl and from 208.7 to 153.1 mg/dl, respectively, P<0.001). However, a favorable reduction in hemostasis parameters (platelet aggregation on extracellular matrix and (alpha2-antiplasmin) was only seen among the nondiabetic patients (from 12.1+/-4.9 to 4.2+/-3.2%, P<0.001). This difference may stem from a less efficient exchange between n-3 and n-6 PUFA in serum phospholipid of the OHD+DM patients. Overall, this 13-day fasting/refeeding method developed by us has proven to cause the rapid exchange of arachidonic acid for eicosapentaenoic acid. It appears to be an effective regimen for the reduction of cardiovascular risk factors (BP, TG and hemostatic variables) in OHD-DM patients and to a lesser extent in OHD+DM patients.

Time dependency of the antihypertensive efficacy of the new renin inhibitor Ro 42-5892.

The objective of this study was to assess the antihypertensive efficacy of the new renin inhibitor Ro 42-5892 in patients with essential hypertension treated with 100 mg once daily orally. This was a double-blind, placebo-controlled, parallel group trial. After three weeks of wash-out and one week of single-blind placebo run-in periods, 25 patients with mild to moderate essential hypertension (sitting DBP between 95 and 114 mmHg) were randomised to receive either placebo (n = 12) or 100 mg of Ro 42-5892 (n = 13) once daily for eight days. On the eighth day, four hours after the oral administration, patients were randomised to receive intravenously either placebo or 10 mg of Ro 42-5892. BP and heart rate were measured repeatedly (hourly for eight hours and at the 24th hour post-dose) on the first and last days of active treatment. Compared with the placebo group, a slight decrease in sitting DBP was observed after the first dose in the Ro 42-5892 group. The decrease in sitting DBP reached significant levels only at six to eight hours post-dosing. In contrast, on the last day of active treatment, a larger, faster and longer decrease in sitting DBP was observed in the Ro 42-5892 group. Thus, the peak effect (-8.9 +/- 1.9 vs. -2.9 +/- 1.3 mmHg, P < 0.01) was reached 1.5 hours post-dosing and the trough effect (24 hours post-dosing) was slightly but significantly lower when compared with the placebo group (-3.0 +/- 1.0 vs -0.3 +/- 0.8 mmHg, P < 0.05, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of an orally active renin inhibitor, Ro 42-5892, in patients with essential hypertension.

Ro 42-5892 (Ro) is a new renin inhibitor that has been shown to be an orally effective compound in primates and in the first exploratory studies in humans. However, no firm conclusions could be drawn from the human trials and therefore the present study was designed to evaluate the antihypertensive efficacy of the compound in a double-blind, placebo-controlled trial. After a 3 week wash-out period and a 1 week single-blind placebo period, 24 patients were randomized to receive once daily orally either placebo or 600 mg Ro 42-5892 (N = 12/group) for 8 days. On the last day of treatment, an intravenous infusion of placebo or 100 mg Ro was given in a double-blind fashion, 4 h after the oral administration. Blood pressure (BP), heart rate (HR), plasma renin activity (PRA), immunoreactive renin (IRR), and plasma Ro levels were measured repeatedly on the first and last days of treatment. After the first oral intake of Ro, sitting diastolic BP dropped significantly from 30 min to 24 h post-dose when compared to placebo (-10.2 +/- 1.2 mm Hg v - 0.4 +/- 2.0 mm Hg at peak and -6.9 +/- 1.8 mm Hg v 1.7 +/- 0.9 mm Hg at trough; P < .01 respectively). The trough effects of Ro and placebo after the 7th and 8th doses were -5.1 +/- 1.6 mm Hg v -0.2 +/- 1.0 mm Hg; P < .05 and -5.4 +/- 1.3 mm Hg v 2.3 +/- 1.2 mm Hg; P < .01, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Does isradipine exert a special early-morning blood pressure-lowering effect?

The blood pressure-lowering effect of isradipine at 1.25-2.5 mg twice daily (taken at 0700 and 1900 h) was assessed in a double-blind study involving 28 men with mild-to-moderate hypertension. After a 4-week placebo period, patients were randomized to receive either isradipine (group I) or placebo (group II) for 8 weeks. At the end of the placebo and active-treatment periods, patients were evaluated by 24-h ambulatory blood pressure monitoring. Data were analyzed according to two time periods: daytime, 1000-2300 h; nighttime and early morning, 2300-1000 h. Intersubject analyses were performed comparing values at the end of placebo with those at the end of active treatment. Intrasubject two-way analysis of variance showed that the time of day or night had no influence on blood pressure changes. Comparison of systolic (SBP) and diastolic (DBP) blood pressures with isradipine indicated that there were significantly greater average decreases in SBP at 0600-0800 h than at 1800-2000 h (p = 0.038), and at 0800-1100 h than at 2000-2300 h (p = 0.045). This was also true for the average decreases in DBP (p = 0.006). In conclusion, isradipine exerts blood pressure control throughout 24 h with a pronounced action during the early morning (0600-0800 h) period.

Twenty-four-hour blood pressure control with isradipine in mild essential hypertension.

The hypotensive effect of isradipine was assessed in 26 male patients, aged 40 to 64 years, with hypertension. After withdrawal of previous antihypertensive treatment and a four-week placebo period, patients were randomized into a double-blind active-treatment period of eight weeks to receive either placebo or 1.25 to 2.5 mg isradipine twice daily. Twenty-four-hour ambulatory blood pressure was measured by Accutracker (Suntech, Oxford, England) after the placebo period and at the end of the active-treatment period. In the isradipine group n = 13), both systolic and diastolic blood pressure and number of blood pressure spikes decreased significantly (P less than .0001), whereas there was a significant increase of these variables in the placebo control group (n = 13). The results of this study indicate that, in these subjects, blood pressure control was achieved throughout the 24-h period by monotherapy with isradipine.

The antihypertensive action of isradipine in mild essential hypertension.

The antihypertensive effect of isradipine compared with placebo was assessed in 28 male patients (aged 40-64 years) with mild-to-moderate essential hypertension. After withdrawal of all previous antihypertensive treatment, these patients were entered into a 4-week placebo period followed by randomization to receive double-blind, for 8 weeks, either placebo (n = 14) or isradipine at 1.25-2.5 mg twice daily (n = 14). Twenty-four-hour ambulatory blood pressure was measured by Accutracker at the end of the placebo period and at the end of active treatment. In the isradipine group, both systolic and diastolic blood pressures decreased significantly (p less than 0.0001) whereas blood pressure increased in those taking placebo. In addition, isradipine as monotherapy controlled blood pressure throughout the day and night, and especially during the early morning, in these patients.

The antihypertensive effect of atenolol and bopindolol in the elderly.

The antihypertensive efficacy and tolerability of two betablockers: atenolol and bopindolol, was compared in a group of 30 elderly subjects aged 64.8 +/- 4.6 years. The daily dose of the two agents was relatively low. Atenolol 50-100 mg and bopindolol 0.5-1.0 mg sufficed to cause reduction of DBP to the target of less than or equal to 95 mm Hg, when applied as monotherapy. This was achieved in 75% of cases with bopindolol and in 93% of cases with atenolol. Atenolol, 50-100 mg/dd, lowered blood pressure from 173.7 +/- 13.2/103.7 +/- 3.0 (weekly) to 155.5 +/- 16.5/86.5 +/- 8.2 mm Hg (week 12) (P less than 0.005) while bopindolol, 0.5-1.0 mg, lowered blood pressure from 171.6 +/- 11.3/104.1 +/- 3.6 to 158.7 +/- 20.9/86.1 +/- 6.0 mm Hg (P less than 0.005). Heart rate was reduced from 80.5 (week 4) to 66.7 +/- 7.3 (week 12) by atenolol (P less than 0.0001), and from 83.7 +/- 11.8 (week 4) to 71.1 +/- 7.5 (week 12) by bopindolol (P less than 0.0001). Between treatment differences: comparisons yielded P values which were not sufficiently low to reject the null hypothesis of no difference between the two treatments. Well-being and short-term memory were not affected by either agent and tolerability of both drugs was good. These findings demonstrate that both bopindolol and atenolol are useful agents for control of hypertension in the elderly.