An intrinsically stable antibody scFv fragment can tolerate the loss of both disulfide bonds and fold correctly

Several observations indicate that a low lipoprotein lipase (LPL)/hepatic lipase (HL) ratio clusters with clinical and laboratory features of atherosclerosis. Antihypertensive treatment can unfavourably interfere with lipid metabolism, counteracting the beneficial effects of lowering blood pressure. We have evaluated the effects of the Ca2+ channel antagonist nitrendipine on tissue LPL and HL in the normal rat. At the dose of 40 mg/day administered intragastrically, a 5-day nitrendipine treatment induced a significant decrease in HL activity in the liver, in comparison to control animals: 656 +/-82 mU/g tissue vs. 814+/-38 mU/g 3 h after the last administration; 640+/-70 mU/g vs. 893+/-101 mU/g 8 h after administration. LPL activity in heart was increased by active treatment: 2542+/-298 vs. 2115+/-244 mU/g in controls 3 h after administration, P < 0.05. At variance, LPL mass, measured 8 h after administration, was decreased in heart of treated rats: 2.38+/-0.4 microg/g tissue vs. 3.88+/-0.3 microg/g in controls. The ratio between heparin-releasable and residual LPL in heart was unaffected by the drug. No changes were observed in LPL activity and mass in soleus muscle or in periepididymal adipose tissue. Our results indicate that nitrendipine, at the dose used, induces changes in lipolytic enzymes of rat tissues that could be beneficial in relation to atherosclerosis. These data encourage further investigations in humans, at the usual therapeutical doses.