Simulated glomerular pressure modulates mesangial cell metalloproteinase activity

AJH-APRIL 1995-VOL.8, NO.4, PART 2

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A9 IMPAIRED NATRIURETIC AND ANP RESPONSES TO mGH SALT INTAKE IN PATffiNTS WI1H LEFT VENTRICULAR DYSFUNCTION. Maria A.E. Rao, Paola Magri, Iolanda Enea, Bruno Memoli, Rosaria Russo. Alessandro F. Mele, Sara Cangianiello, Massimo Volpe.... University Federico II, Napoli, Italy The aim of this study was to investigate the natriuretic response to salt intake in the early or mild stages of heart failure in relation to the behavior of natriuretic peptides. Thus, 22 patients with asymptomatic left ventricular (LV) systolic dysfunction (NYHA Class: 1·11, ejection fraction =35±2%) and 16 matched normal subjects (N)were shifted from low(NaCI lOO mEq/day) to high salt diet (2S0 mEq/day) for 8 days under strictly balanced metabolic conditions. N achieved neutral sodium balance by day 4 ofbigh salt diet, while the plasma levels of both atrial (ANP) and B-type (BNP) natriuretic peptides increased significantly. In contrast. in patients with 'iL V dysfunction a significantly higher positive cumulative sQdium balance (+338:1:39 mEq vs +220±29 mEq in N, F=3.61, p
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SIMULATED GLOMERULAR PRESSURE MODULATES TRANSMIGRATION OF MONOCYlcS p, Singh:ll'~. P. S:lg'lr. S. Gupln. P. 0:11'11. M. ArYll. N. Gibbons ..."J i. MlllI:UI:I.

Long Islanl! Jewish Me:uiclll Center, New Hyde Park, New York. Long Island Campu» IiII' Alber: Einstein Medical Center, Bronx. New York, MillMilln III' monocyres into thtlgllllnerlllllr mesangium has been t1"Ill11llslrulcu III he: of Pllthol!lmic import.lnrc tilt the: development of gimlle:rulllsde:msis in the remnant kidney as well as puromycin aminonucleoside-imluced nephrosis models. We: investigated whether increased glum"nillir cspillary pressure: mny he playing II role in the tnmsmigmliml lIf monocytes, Wesh!Jied millrat;on of U937 monocyte across II gelatin coated filter (pure size. 5 J.l11l) in II modified Boyden chamber (MBC). To' simulate ~llJIm:flIltlr c"pill"ry pressure we have ue:signed a pressure c0l11l'artJ11elll (PC) which has a re:glll:lte:l! flow of CO~ lind IIiI' at 37°C, EIIUIII number Ill' U937 rnonocytes (IO'/ml) were instilled in the upper chambers and an aliquot 01' RPMI in the lower chambers ofthe MBC. The MBC wus k~ll/ in PC tor 120minutes HI H Vllrillhle mean pressure (45.75. and 100 nun H~). Paralle] studie» (control) were1I1so performed outside the: PC. The: mignued mnnncytes on thelower!:iuc: ot' tillerwere siaiut:t! :lIItl COUl1lc:t! in 8 nmllum tidJs untle:r light microscopll. Resu/ts rc:presenl n:~1lI1S ± SEMfHPF frnm 4 s<:ls of e:xpe:ril11e:nts. Pressure (nll11 H~) U 40-45 0 70-75 0 95-100 tl.7±O.2 14.7 ±O.4·~ 11.6±0.2 Ill.S±O.I'" 12.S±0.2 17.7±O.201<.oI
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SfMULATED GLOMERULAR PRESSURE MODULATES MESANGJAL CELL METALLOPROTE/NASE ACTIVITY P, Singhal*. S. Sagar", P. G'II·g. M. Ary41 and J. Mattana. Long Island Jewish Medlcal Center, New Hyde Park, New York. L. I, Campus tilr Aloerl Einstein Cullege tlf Medicine, N, Y. Glom~rllltll· hypertension has been considered to play an importunt role in the development of glomerulosclerosis (GS). M~silngiill expansion. a precursor of may he dependent not only on synthesis IIf matrix hut also lin the degradation of the deposited matrix. In the present ~ludy we Investigated theeffect of ~ill1ulatctf glumerular pressure on metulloprotelnase-z activity (MPA. measured as degradation Ill' g~llItjn) lit' mesanglal cells (MC). Til slmulate glomerular pressure condltlons we have used an in vitro mechanical ~tl'ctch/l'claxation system (SRS) as well ::5 'In altcwative system which allowed direct application of pressure (DP) on MC. MCs were grown either under control (no pressure) condltion. stretch'relaxatiun. or Jirect mean pressure of 45·50mm Hg (/lhysioll1gic glomerular pressure). MPA was measured by using hkuln-avidln ussay lint! zymogurphy, Results represent means ± SEM (ng gelatin degmt!edlllg proteinjtrom 4 sets of experiments, Slrclch/n:!;lx;U lun Direct pressure contro I 45 mm /-I g CIIIlI I'll I 45 mill Hg 4.5±1.1 15.3±J.1"' O,35±O.OI 0.59±O.01** :l:p c: 0,00I cOlllpilred with Cllllll'Ol;**P
Monocytes, mesangilll1l, glome:ntlar hypllrlllnsion, glulllerulusckrusis. tran"migralion

GLOMERULAR (G) MATRIX MATELLOPROTEINASE (mMP) MODULATES DEVELOPMENT OF FOCAL AND SEGMENTAL GLOMERULOSCLEROSIS (FSGS) ~o, PC Singhal. Long Island Jewish Medical Center, NY andNassau County Medical Center, EastMeadow, NY FSGS represents a final pathological pattern of a number of human kidney (K) disorders. Among laboratory animals both puromycin aminonucleoside (PAN) and hypertension produce a similar histologic pattern. Westudied theG mMP activity in the development of FSGS. Dahl saIt sensitive (5S) & saltresistant (SR) rats were fed on 8 % saltdiet for 6 wk. Laparotomy was performed under anaesthesia and a K biopsy was taken. K were removed afterhaving perfused bloodless in situ with phosphate buffered saline and the G were isolated. G were incubated with [3H] gelatin at 37°Cx18 hours Sprague-Dawley rats were administered subcu.aneously either saline (S) or S containing PAN (1.67 mg/IOO g b.w.) daily for 7 days. K biopsy was taken & G were isolated on day 10 as above. In another set of rats Q were isolated at 6 weeks. Pathology was consistent with FSGS in SS and PAN ratsat 6 wk. G mMP is expressed as thecpm released on degradation of gelatin/ug of G protein. SR rats (n:::6) S5 rats (n=6) G-mMP 148±12 7.3±9° 10Days 42 Pays PAN (n=6) S (n=6) PAN (0=6) S (n:::6) Q·mMP 60±4 Sl±7 12±1° 31±5 P <0.01 as compated to SR or S treated rats. These results suggest that G-mMP activity was reduced at 6 wk in SS rats and in PAN treat~ rats. The reduced G-mMP activity may be playing a role in the expansion of matrix and tlubsequellt FSGS. Key Words: Glomerulosclerosis, Hypertension, Puromycin aminonucleoside, Metalloproteinase