Phosphodiesterase Inhibitors Correct Resistance

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4 '. 1996. Phosphodiesterase. Inhibitors Correct Resistance to .... The resistance is not related to an alteration ..... Model 943, Lexington,. MA). Plasma and urine.
Phosphodiesterase Natriuretic Peptides Jean-Pierre William

Valentin,

G. Couser,

Inhibitors Correct Resistance in Rats with Heymann

Wei-Zhong and

Ving,

Michael

Leonardo

A. Sechi,

W.-Z. Ying. K-I. phreys. Division of Nephrology. Hospital. University of California Francisco. CA

Ling. C. Qiu, M.H. HumSan Francisco General at San Francisco, San

Sechi, Medicine,

Department Udine, Italy

Hypertension Unit. University of Udine,

L.A.

Couser. Division of Washington. Seattle, WA

Nephrology,

W.G.

(J.

Am.

Soc.

Nephrol.

1996;

nephrotic

abnormal

sodium

of Internal

natriuretic infused

syndrome

University

of

response both atrial natriuretic

presented plasma

is characterized

reflected

to volume peptide

here examined ANP concentration

the

by

in a blunted

expansion (ANP). The

relationships and urinary

and to studies

among sodium

days

after ip injection of anti-Fx1A antiserum, rats were proteinuric and had a blunted natriuretic response to intravenous infusion of isotonic saline (2% body weight, given over 5 mm). Thirty mm after the onset of

nephritic

plasma the same

rats,

ANP concentration was inextent in both normal and

compared

with

their

respective

hydra-

penic controls. Despite this increase, UCGMPV was significantly less in nephritic rats after the saline infuslon. Accumulation of cGMP by isolated glomeruli and IMCD cells from nephritic rats after incubation with ANP and RNP was also significantly reduced,

compared with normal rats. This difference was not related to differences in either density or affinity of renal ANP receptors, but was abolished when accumulation of cGMP was measured in the presence of

1

Received

2 Portions

November of

this

1992;40:181A. 3

Correspondence

SFGH, University

15, 1995.

work

and

were

J Am Soc

Accepted

December

previously

published

Nephroi

1991 ;3:448A.

to Dr. M.H. Humphreys, of Caiifornia

at San Francisco,

in

Division

12, 1995. abstract

1046.6673/0704.0582$03.OO/O Journal of the American Society of Nephroiogy copyright © 1996 by the American Society of Nephrology

582

form

of Nephrology.

San Francisco,

(PDE).

in

din

Box CA 94143.

of cyclic

Infusion

nephritic

Qiu,

orZaprinast,

nucleotide

of Zaprinast

rats normalized

cGMP-PDE ±

32

protein,