Nebivolol was compared in a dose of 5 mg once daily with enalapril 10 mg once daily over 7 months in a double-blind randomised trial in essential hypertension. The two drugs had very similar sustained effects in lowering both systolic and diastolic pressures; neither had an orthostatic component. Both drugs were well-tolerated. No haematological, biochemical, or urinary abnormalities were seen.

Background: Meperidine proved to be more effective in treatment of shivering than equianalgesic doses of other opioids, especially pure -agonists. Further, meperidine has well known nonopioid actions including agonistic effects at ␣ 2 -adrenoceptors in vitro. Accordingly, the authors investigated nonopioid receptor-mediated effects of meperidine on thermoregulation using a mice model of nonshivering thermogenesis. To differentiate conceivable ␣ 2 -adrenoceptor subtype specific interactions the authors analyzed wild-type mice and knock-out mice with deletion of the ␣ 2A -, ␣ 2B -, or ␣ 2C -adrenoceptor.Methods: Ten mice per group (n ‫؍‬ 60) were injected with saline, meperidine (20 mg/kg), saline plus naloxone (125 g/ kg), meperidine plus naloxone, fentanyl (50 g/kg) plus naloxone, or meperidine plus atipamezole (2 mg/kg) intraperitoneally. Each mouse was subjected to the six different treatments. Then they were positioned into a plexiglas chamber where rectal temperature and mixed expired carbon dioxide were measured while whole body cooling was performed. Maximum response intensity and thermoregulatory threshold temperature of nonshivering thermogenesis were analyzed.Results: Meperidine decreased the thermoregulatory threshold temperature in wild-type mice and ␣ 2B -and ␣ 2C -adrenoceptor knock-out mice. This effect ended after injection of the ␣ 2 -adrenoceptor antagonist atipamezole. In wild-type and ␣ 2B -adrenoceptor knock-out mice, the decrease of thermoregulatory threshold was not reversible by administration of the opioid receptor antagonist naloxone. In contrast, in ␣ 2A -adrenoceptor knock-out mice, no decline of thermoregulatory threshold following meperidine injection was detectable. Maximum response intensity of nonshivering thermogenesis was comparable in all groups.Conclusions: The authors' results suggest a major role of ␣ 2 -adrenoceptors, especially the ␣ 2A subtype, in the mediation of thermoregulatory effects caused by meperidine in mice.

SummaryA total of 130 patients with mild to moderate hypertension were recruited to an open study and treated with the vascular selective calcium antagonist felodipine (10 to 40mg once daily) for I year. For patients completing the study, median lipid concentrations (mmoIfL) at baseline were: total cholesterol 6.50, triglycerides 1.44, low density lipoprotein (LDL) 4.20, and high density lipoprotein (HDL) 1.40. Plasma concentrations of total cholesterol, triglycerides and LDL were essentially unchanged during the study, while there was a statistically significant increase in HDL concentration which reflected in a significant decrease in the LDL/HDL ratio; these changes were about 5% in magnitude. Blood pressure was well controlled during treatment and adverse effects were principally related to vasodilation, In total 13 patients were withdrawn during the study, 10 of these due to adverse events. In conclusion, long term antihypertensive treatment with felodipine does not adversely affect plasma lipids. In fact, there was a slight increase in HDL, indicating a possible favourable action.

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