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1 The cardiovascular and vasorelaxant effects of (+)-glaucine and of a semisynthetic derivative (N-carbethoxysecoglaucine) were studied in rats. 2 N-carbethoxysecoglaucine did not modify either systolic arterial pressure or heart rate values in conscious (25 mg kg-', p.o.) and anaesthetized normotensive rats (5 mg kg ', i.v.) 3 In conscious normotensive rats, oral administration of (+)-glaucine (25 mg kg-') did not modify either systolic arterial pressure or heart rate.4 In anaesthetized normotensive rats, (+)-glaucine (5 mg kg-', i.v.) produced a remarkable fall in mean arterial pressure (MAP) accompanied by a significant decrease in heart rate. In the same preparation, (+ )-glaucine (5 mg kg-', i.v.) did not modify the cardiovascular effects induced by noradrenaline (NA) (5 Ag kg-') and 5-hydroxytryptamine (5-HT) (300 1tg kg-') but markedly inhibited those induced by nicotine (200 Ig kg-').5 In isolated intact aorta of rat, (+)-glaucine (0.15-5tiM) competitively inhibited the contractions induced by NA (with a pA2 value of 7.14) and non-competitively those induced by 5-HT (in normal Krebs solution) and Ca2+ (in depolarizing Ca2+-free high-K+ 50 mM solution), with depression of the maximal response and with pD2' values of 5.56 and 5.26, respectively. 6 In experiments in Ca2+-free medium, (+)-glaucine (3 JAM) inhibited the contractions induced by NA and had no effect on either 5-HT-or caffeine-induced contractions. 7 Furthermore, in the experiments with radioactive Ca2+, (+)-glaucine (3 JAM) did not modify the basal uptake of 45Ca2+ but strongly inhibited the influx of 45Ca2+ induced by NA, 5-HT and K+. 8 (+)-Glaucine (5JM) had no effect on rate and force of contraction in rat isolated atria. 9 These results indicate that: (a) the cardiovascular effects (hypotension and bradycardia) of (+)-glaucine in anaesthetized normotensive rats (5 mg kg-') may be due, at least in part, to a ganglioplexic effect; (b) the vasorelaxant action of ( + )-glaucine (0.15-5 JM) in rat isolated aorta can be attributed to an a,-adrenoceptor blocking property (which may explain its inhibition of noradrenaline-induced 45Ca2+ influx and contractions in normal Krebs solution and noradrenaline-induced contractions in Ca2+-free medium) and to a Ca2+-antagonist activity (which may be responsible, at least in part, for the inhibition of 45Ca2+ uptake induced by NA, 5-HT and K+ and the contractions induced by both NA and 5-HT in normal Krebs solution and by Ca2+ in Ca2+-free high-K+ medium) and (c) there is no correlation between the mechanisms of action observed for (+ )-glaucine in vivo and in vitro, which suggests that the vasorelaxant activity of this alkaloid does not contribute to its hypotensive activity.

The effects of a polysaccharide extract from the seaweed Fucus vesiculosus on serum lipid levels were evaluated in normal and hyperlipaemic rats. In screening tests of immediate (4 h) effects in normal rats, the highest dose assayed (10 mgkg) significantly lowered total cholesterol and low-density-lipoprotein-cholesterol (LDLcholesterol) levels, and significantly increased the antiatherogenic index (AAI, i.e. 100 x HDL-C/[totalC-HDL-C]).In screening tests of short-term (24 h) effects in %ton-induced-hyperlipaemic (TIH) rats, the extract caused marked dose-dependent reductions in total cholesterol and triglyceride levels. Tests in TIH rats suggested that the observed hypolipaemic activity was due to inhibition of cholesterol synthesis. Subsequent tests of longer-term (12 day) effects in diet-induced-hyperlipaemic rats provided support for this hypothesis: the extract at 10 mgkg did not have significant effects on total cholesterol or LDL-cholesterol, but caused moderate increases in highdensity-lipoprotein-cholesterol (HDL-cholesterol) level and AAI.