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Circulation Research. 1995;76:276-283

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(Circulation Research. 1995;76:276-283.)
© 1995 American Heart Association, Inc.


Articles

Circulating Leukocyte Counts, Activation, and Degranulation in Dahl Hypertensive Rats

K. Shen, F. A. DeLano, B. W. Zweifach, G. W. Schmid-Schönbein

From the Institute for Biomedical Engineering, University of California, San Diego, La Jolla.

Correspondence to Dr G.W. Schmid-Schönbein, Institute for Biomedical Engineering, University of California, San Diego, La Jolla, CA 92093-0412.

Abstract Previous evidence has shown that rats with spontaneous hypertension have on average about twice as many circulating leukocytes in comparison with their normotensive counterparts, the Wistar-Kyoto rats. Since such high levels of leukocytes may increase the risk for vascular complications for hypertensive animals, it is useful to ascertain whether a comparable derangement is present in other forms of hypertension. The present study deals with the properties of the circulating leukocytes in rats exhibiting another form of experimental hypertension; Dahl salt-sensitive (Dahl-S) hypertensive rats were compared with Dahl salt-resistant (Dahl-R) control rats. Measurements were performed to determine the following: circulating hematocrit levels, leukocyte counts, differential counts, number of activated leukocytes (by means of nitro blue tetrazolium [NBT] reduction), leukocyte adhesion in vitro and neutrophil CD-18 expression, alkaline phosphatase activity in individual neutrophils and in the plasma, and myeloperoxidase activity in neutrophils. The experimental cohort consisted of Dahl-S and Dahl-R rats maintained for a 6-week period on a 6% NaCl diet. The results show a highly significant elevation in the number of total leukocytes, neutrophil and monocyte counts, and NBT-positive neutrophils and monocytes in Dahl-S but not Dahl-R rats. There was a significant loss of alkaline phosphatase and myeloperoxidase activity in the neutrophils of the salt-treated Dahl-S rats but not in the neutrophils of the untreated Dahl-S or Dahl-R rats. No significant differences were found in neutrophil adhesion under in vitro test conditions between the two strains maintained on the salt diet. In salt-treated Dahl-S rats, there was a reduced expression of ß2 integrins (CD-18) in neutrophils, although a higher fraction of the circulating neutrophils exhibited above-threshold CD-18 expression. These results indicate an increased number of circulating neutrophils and monocytes in Dahl-S rats that are in an activated state and undergo spontaneous degranulation in the circulation without exhibiting elevated levels of membrane adhesive properties. Such circulating leukocyte kinetics may contribute to a range of vascular complications in the hypertensive rats.


Key Words: salt hypertension • adhesion • nitro blue tetrazolium reduction • alkaline phosphatase




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