PLASMA LIPOPROTEINS REGULATE APOLIPOPROTEIN SYNTHESIS IN CULTURED HEPATOCYTES

A. Pletran@elo, R. Tiozzo, M. Ghisellini, R. Ci~gi, L. Albertazzi, E. Ventura and S. Calandra. Istituti di Clinica Medica III and Patologia Generale, University of Modena, Modena, Italy

The liver is the major source of plasma lipoproteins. However, direct studies of the regula tion of lipoprotein synthesis in the liver under physiological conditions are lacking. In the present study we investigated whether plasma lipoproteins and/or plasma lipid components could regulate the apolipoprotein synthesis in minimal deviation rat hepatoma cells (FAO), which can synthesize several plasma proteins in~uding apolipoproteins. Cells were incubated for 12-24 hours in serum-free media containing --S-methionine either in the absence or in the presence of various plasma lipid components. In the presence of 5-1Cr~ rat plasma,apolipo_ protein synthesis increased by 2-3 fold, whereas lipoprotein-deficient serum had no effects. Rat plasma lipoprotein fractions (d<1.090 g/ml; d 1.090-1.210 g/ml) induced a 6-10 fold in crease of apoliporotein synthesis: d<I.090 g/mi lipoprotein fraction, which had the highest cholesterol content and bound to specific high affinity hepatocytes receptors(E and B), was the most effective at concentration ranging from 200 to 800 ~g/ml of lipoprotein-protein. When lipid extracted from lipoproteins were added to the medium, a comparable increase of apo_ protein syntehsiswas observed. Under all these experimental conditions the density profile o£ secreted lipoproteir~shifted to the lighter density classes and the major stimulatory ef fect involved apo E synthesis. In the presence of a]hxnirFtox~fatty acids (0.65-1.5OMM), apo_ lipoprotein synthesis was unaffected. Our data provide evidence that the synthesis of some apolipoproteins (i.e. apo E) are under the control of lipoprotein-lipids.

EVIDENCE OF ALPHAI-ADRENORECEPTORS HYPERRESPONSIVENESS IN CIRRHOSIS WITH ASCITES M.Pinzani, B.M. Fusco*, M.Alessandri*, G. Laff i , F.Marra and P.Gentil ini. C-linica Medica I I and *Patologia Medica e Farmacologia Clinica, University of Florence, 1-50134 Viale Morgagni, 85, Florence, ITALY.

Cirrhotic patients with ascites (C) frequently show raised plasma norepinephrine (NOR) levels associated with marked arterial hypotension, reduced vascular resistances and impaired cardiovascular responsiveness. Alphal-adrenoreceptors (~ I ) play an important role in the regulation of blood pressure and studies specif ical ly investigating.their react iv i ty in this c l in ica l setting are s t i l l lacking. Monitoring of the peripheral neuroeffector junction, d i rect ly in vivo, has recently become more feasible using the non-invasive computerized pupillometry technique. The neuromuscular junction of the i r i s is mainly supplied by a l and the responses of the i r i s muscle to autonomically acting drugs are highly reproducible. We studied 15 C and 15 age-matched healthy subjects (H). After basal pupil lary area (PA) measurements, one drop of an aqueous solution of I% tyramine (TYR) (TYR induces a massive release of NOR from the SNS nerve ending) was ins t i l led into a conjunctival sac and measurements of PA were performed every 30 min for 3.5 hrs. After two days, al l subjects received one drop of an aqueous solution of I% phenylephrine (PH, a powerful al stimulant) into the same eye previously treated with TYR and determinations of PA were performed with the same modalities. Responses were calculated as the percentage increase of the basal PA. In C, a weaker and shorter response was observed after TYR (p~O.05 after 90 and 120 min), whereas PH induced a s igni f icant ly greater and longer-lasting increase in PA when compared to H (p~O.05 after 60,150,180 min; p~O.Ol after 210 min). Our results suggest a possibleal hyperresponsive- ness in C consequent to decreased NOR stores in the peripheral SNS endings.

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