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D Seiffge

Publications and source records attributed to D Seiffge.

At least 19 recordsLinked to original sources
PubMed2001

Antibodies to PECAM-1 and glucocorticoids reduce leukocyte adhesion in adjuvant arthritis of the rat knee synovium in vivo.

OBJECTIVE AND DESIGN: To demonstrate the effect of monoclonal antibodies to the adhesion-molecule PECAM-1 (CD31) and of prednisolone on leukocyte adhesion in rat adjuvant arthritis. MATERIAL: Adjuvant arthritis was induced in male CD-rats (five groups of n = 6) 18 days prior to measurements. TREATMENT: Mouse-monoclonal antibody to rat CD-31 at 200 microg/kg or prednisolone at 24 mg/kg were administered i.v. 15 minutes prior to measurements. METHODS: Venules within the intact rat-knee synovium were focused by confocal laser scanning microscopy. Numbers of rolling and adherent leukocytes were assessed in vivo. RESULTS: Induction of arthritis significantly increased rolling and adherent leukocytes compared to healthy controls. Both monoclonal antibodies to PECAM-1 and prednisolone significantly reduced adherent, but not rolling leukocytes in arthritic animals. CONCLUSIONS: The method used is well suited for in vivo quantification of leukocyte adhesion under the influence of antiadhesive therapies. PECAM-1 might be an interesting target for novel therapies in rheumatoid arthritis.

Animals↗
PubMed1999

Confocal laser scanning microscopy of leukocyte adhesion in the microcirculation of the inflamed rat knee joint capsule.

OBJECTIVE: The aim of the study was to develop a model of intravital microscopy of the microcirculation of the rat knee joint capsule in acute inflammation with the help of confocal laser scanning microscopy (CLSM). METHODS: The microvascular architecture of the joint capsule was investigated by the use of corrosion casting techniques. Knee joint capsule microcirculation of anesthetized rats could be visualized by dissection of the ligamentum infrapatellare rectum and application of a CLSM. Rhodamine 6G was used as a leukocyte marker. An acute arthritis was induced by intraarticular injection of 0.1 mL of 1% Carrageenan solution. Each experiment lasted for 3 h. Leukocyte adhesion (LA) was measured in 100 microns of vessel length. Leukocyte-rolling velocity (Vwbc), systemic leukocyte count (WBC), and differential blood count (DBC) were monitored in defined intervals. Finally, myeloperoxidase (MPO) activity in frozen-tissue homogenate served as a parameter of neutrophil content. RESULTS: Leukocyte adhesion in carrageenan-treated animals was 9.9 +/- 0.2 leukocytes/100 microns vessel (mean +/- SD; n = 6), while sham- treated animals had 2.8 +/- 0.2. Monoclonal antibodies (MAb) to alpha 4 integrin (0.2 mg/kg) reduced LA to 2.6 +/- 0.1 (p < 0.01). Vwbc/gamma quotients were 0.37 micron s/s in control animals and 0.53 micron s/s in anti-alpha 4-treated animals (p < 0.01). Changes in DBC were marked by lymphopenia and granulocytosis after 180 min. At this time point-control animals had 5.1 G/L LC and 2.6 G/I PMN. Animals treated with unspecific antibody had 4.7 G/L LC and 4.9 G/L PMN, while anti-alpha 4-treated animals had 10.6 G/L LC and 2.4 G/L PMN. Photometrically determined extinction of oxidized tetramethylbenzidine (TMB; measure for MPO content) was 1.058 +/- 0.555 in control animals and 0.245 +/- 0.093 in sham-treated animals. Tissue homogenate from unspecific IgG treated group had 0.776 +/- 0.140 and from anti-alpha 4-group 0.334 +/- 0.155 (p < 0.05). CONCLUSIONS: Confocal laser scanning microscopy is a tool for the study of the microcirculation in nontransparent organs. The microcirculation of the acutely inflamed rat knee joint capsule can serve as a model of integrin-mediated LA in vivo. Antiadhesive treatment of animals can reduce the tissue infiltration with inflammatory cells.

Animals↗
PubMed1998

In vivo analysis of antithrombotic effectiveness of recombinant hirudin on microvascular thrombus formation and recanalization.

PURPOSE: This study was undertaken to evaluate in vivo the effect of recombinant hirudin (r-hirudin [HBW 023]), a potent thrombin inhibitor, on the process of microvascular thrombus formation and recanalization. METHODS: Thrombosis was induced photochemically in distinct arterioles (n = 25) and venules (n = 30) of the ear of 16 hairless hr/hr mice (8 to 10 weeks old, 25 to 30 g of body weight). r-Hirudin (1 mg/kg of body weight) was administered intravenously directly before thrombus induction; saline-treated animals served as controls. Thrombus formation (i.e., first platelet deposition at the endothelial lining [FPD]; inner luminal diameter reduction to 50% [D/2]; complete vessel occlusion [CVO]), vessel recanalization, microcirculatory parameters, and leukocyte-endothelial cell interaction were analyzed by means of intravital fluorescence microscopy. RESULTS: Hirudin significantly delayed the process of thrombus formation compared with saline-treated controls in both arterioles (FPD: 381 +/- 80 vs 137 +/- 25 seconds, P < 0.05; D/2: 627 +/- 49 vs 501 +/- 71 seconds; CVO: 925 +/- 78 vs 854 +/- 60 seconds) and venules (FPD: 173 +/- 11 vs 59 +/- 4 seconds; D/2: 342 +/- 54 vs 228 +/- 27 seconds; CVO: 541 +/- 85 vs 344 +/- 43 seconds; P < 0.05). In addition, r-hirudin-treated animals showed an increased rate of vessel recanalization at 24 hours after thrombus induction (arterioles: 54% [7 of 13] vs 0% [0 of 12], P < 0.05; venules: 77% [10 of 13] vs 53% [9 of 17]), whereas microcirculatory parameters and leukocyte-endothelial cell interaction were not affected. CONCLUSION: Our data indicate that r-hirudin not only counteracts the process of thrombus formation but also promotes vessel recanalization, thus supporting its use in clinical microvascular surgery.

Animals↗
PubMed1997

Effects of tiaprofenic acid on urinary pyridinium crosslinks in adjuvant arthritic rats: comparison with doxycycline.

OBJECTIVE AND DESIGN: To study the effects of tiaprofenic acid and doxycycline on urinary pyridinium crosslinks and paw swelling in adjuvant arthritic rats, and to gain additional information on the drugs' inhibitory potential vs. in vitro targets, such as enzyme activity of matrix metalloproteinases and cytokine generation. MATERIAL: 124 male Wistar Lewis rats; for the in vitro studies human matrix metalloproteinases and human mononuclear cells were used. TREATMENT: Arthritis was induced by injection of complete Freund adjuvant. Drugs (2, 15, 50 mg tiaprofenic acid/kg; 5, 15, 30 mg doxycycline/kg) were administered daily p.o. until day 21. In the in vitro studies 10-1000 mumoles/l of these drugs were used. METHODS: Urinary levels of pyridinoline and deoxypyridinoline, determined by HPLC/fluorescence, and paw volumes were the measurements in the rat study. In the in vitro studies enzyme activities were assessed using fluorogenic peptide substrates; cytokines were determined by ELISA. RESULTS: On day 21 of disease crosslink excretion was about twofold higher compared to the healthy controls. After administering daily 15 or 30 mg/kg tiaprofenic acid p.o. this increase was almost completely prevented whereas the paw volumes were suppressed by about 50%. Up to 50 mg/kg doxycycline did not display significant suppressive effects on crosslinks and paw volumes. In vitro 50-100 mumol/l of both drugs inhibited the activities of selected metallo-proteinases, but only doxycycline suppressed the generation of IL-1 beta/TNF alpha in human mononuclear cells, whereas tiaprofenic acid was virtually inactive in that model. CONCLUSIONS: In arthritic rats tiaprofenic acid has not only the capability to suppress paw inflammation, but also to prevent with high potency the excretion of pyridinium crosslinks. Doxycycline without inherent antiinflammatory activity does not exhibit such preserving effects on collagen degradation in this model. Thus the mode of action of cartilage protecting drugs within the complex pathogenesis of arthritis will need further elucidation.

Animals↗
PubMed1997

Pentoxifylline: its influence on the interaction of blood cells with the vessel wall.

PTX counteracts the increased microvessel permeability which is a feature of the inflammatory aspect of atherogenesis. Furthermore, PTX inhibits oxLDL-induced leukocyte adhesion and, via its positive influence over fibrinolysis and anti-aggregatory factors (e.g. prostacyclin), inhibits thrombus formation. PTX thereby preserves the integrity of the walls of the microcirculatory blood vessels, while reducing the likelihood of thrombosis and its potentially life-threatening sequelae.

Animals↗
PubMed1996

Protective effects of monoclonal antibody to VLA-4 on leukocyte adhesion and course of disease in adjuvant arthritis in rats.

OBJECTIVE: Leukocyte adhesion to the endothelium of postcapillary venules is considered an important step in the inflammatory response. Cell adhesion molecules have been found to play a role in virtually every cellular interaction from inflammation to reperfusion injury. The purpose of this study was to determine the extent of leukocyte adhesion during the development of adjuvant arthritis in rats, and the putative inhibitory effect of a monoclonal antibody (Mab) to very late activation antigen-4 (VLA-4) on leukocyte adhesion and on arthritic disease. METHODS: Adjuvant arthritis was induced in rats by subdermal injection of Freund's adjuvant and arthritis index quantified on the 18th day of disease. Number of rolling, adherent leukocytes/100 microns venule and blood cell velocity were quantified in mesenteric venules (20-30 microns diameter and 100 microns length) of Wistar-Lewis rats, using intravital microscopy. RESULTS: We administered a Mab to rat VLA-4, alpha 4-subunit, at a dose of 1 mg/kg intravenously on Days 1, 9, and 17 to the arthritic rats. Both variables measured in mesenteric venules were reduced. Leukocyte rolling was partially inhibited (by 57%), whereas leukocyte adhesion was totally inhibited (by 94%). In addition, the arthritis index decreased by 54%. Nonbinding isotype mouse IgG1 control antibody did not affect either of the variables. CONCLUSION: Leukocyte adhesion in mesenteric venules of adjuvant arthritic rats involves VLA-4 interaction with an unknown endothelial ligand, which is completely inhibited by Mab to rat VLA-4, indicating a promising effect on clinical symptoms.

Animals↗
PubMed1995

Pharmacological characterization of a new 4-amidinophenyl-alanine thrombin-inhibitor (CRC 220).

The new thrombin inhibitor CRC 220 was characterized in vivo for its antithrombotic effects. CRC 220 led to a dose-dependent prolongation of clotting parameters as determined in rats, rabbits, dogs, sheeps, pigs and monkeys. We evaluated the efficacy of CRC 220 to prevent thrombus formation in arteries and in the microcirculation in different animal models. In a rabbit model of tissue factor-induced coagulation activation, infusion of 0.5 mg/kg x h CRC 220 (3 hours) led to a significant prevention of fibrinogen decrease. In a rat model of lethal LPS-induced DIC CRC 220 significantly prevented the mortality rate after a 4h-infusion of 0.75 mg/kg x h. Thrombin-induced platelet aggregation in rat lungs could be prevented by the i.v. bolus injection of CRC 220. A dose of 0.3 mg/kg leads to a reduction of more than 80% of platelet deposition in the lung, significant inhibition was still observed 90 minutes after CRC 220 administration; at this time the inhibitor had already been cleared from plasma. Arterial thrombosis was induced in rabbits by squeezing and stenosis of the A. carotis. The i.v. bolus administration of CRC 220 dose-dependently prevented thrombus formation, an ED50 of 0.03 mg/kg was calculated. This dose was associated with only a minor prolongation of aPTT.

Animals↗
PubMed1995

Mediator-induced changes in macromolecular permeability in the rat mesenteric microcirculation.

An intravital fluorescence microscopic method for measurement of changes in macromolecular permeability has been established in the mesenterial microcirculation of the rat. After exteriorization of the fat-free distal part of the ileal mesentery, a 1-hr period of stabilization was followed by the injection of FITC-labeled macromolecules. Five minutes later, histamine, leukotriene B4, or leukotriene C4 was topically applied to the tissue by means of a micromanipulator. Areas of 1 mm2 were videotaped with a SIT camera. The fluorescence intensity of these areas was measured by an analogous video image processing system and displayed as gray value histograms. The shift of the frequency of gray levels from lower to upper regions could be attributed to an increase in light intensity in the mesentery, indicating an increase in vessel wall permeability. The sites of action of histamine and leukotriene C4 were very similar. Both mediators affected mainly the larger collecting venules. In contrast, leukotriene B4 exerted its effect at postcapillary venules. Moreover, leukotriene B4-induced extravasation was inhibited by superoxide dismutase, suggesting an involvement of oxygen radicals. The studies with histamine alone and with H1- and H2-antagonists demonstrated that histamine-induced extravasation in the rat mesentery was mediated by H1-histamine receptors. The present study introduces an experimental model for the measurement of changes in macromolecular permeability, which is useful for studying mediator effects and their pharmacological inhibition in the microcirculation of the rat mesentery.

Animals↗
PubMed1995

Inhibitory effects of pentoxifylline on LPS-induced leukocyte adhesion and macromolecular extravasation in the microcirculation.

Pentoxifylline (PTX) has been shown to combat effectively endotoxin induced symptoms of shock or inflammation by reducing both leukocyte activation and endogenous cytokine formation. With regard to blood perfusion, inflammation is defined as a local reaction to injury of the living microvasculature and its content. Leukocyte margination, rolling, adhesion, and emigration is mediated by adhesion molecules along the endothelium of postcapillary venules and is considered to be an important step in the inflammatory response. Changes in the vascular integrity can be estimated in terms of increased extravasation of macromolecules. Using intravital microscopy with the help of an analogous video image processing system we measured the effect of PTX on lipopolysaccharide (LPS, 15 mg/kg i.v.) induced leukocyte adhesion and extravasation of FITC-rat serum albumin (FITC-RSA) in rat mesenteric venules. The changes in vascular permeability correlates significantly (r = 0.75) with a locally increased number of adherent leukocytes. PTX significantly inhibits both leukocyte adhesion and extravasation of FITC-RSA dose dependently. Our results indicate that PTX effectively preserves vascular integrity in the microcirculation by acting primarily on LPS-induced leukocyte adhesion.

Animals↗
PubMed1995

In vitro effects of oxidized low density lipoprotein on CD11b/CD18 and L-selectin presentation on neutrophils and monocytes with relevance for the in vivo situation.

Oxidized LDL (oxLDL) has been identified as a potent stimulus of leukocyte adhesion to endothelium, a hallmark of early atherogenesis. A cytofluorometric study was performed to further characterize the mechanisms by which oxLDL stimulates the rapid adhesion of leukocytes to endothelium in vitro and in vivo. Incubation (30 minutes at 37 C) of whole blood (diluted with buffered saline to 1 x 10(6) leukocytes/ml) with oxLDL (0.85 mg LDL cholesterol/ml; oxidized by 7.5 mumol/L Cu2+ for 18 hours) but not native LDL stimulated the upregulation of CD11b/CD18 adhesion receptors on neutrophils (anti-leu-15 binding: 178 +/- 16% of baseline, P < 0.01, means +/- SD of n = 10 experiments) and on monocytes (169 +/- 34% of baseline, P < 0.01). This phenomenon was almost entirely inhibited by n-butanol or the vasoactive drug pentoxifylline (PTX), which also significantly reduced oxLDL-induced leukocyte adhesion to venular and arteriolar endothelium, as assessed by intravital microscopy on the dorsal skinfold chamber in hamsters (venules: 49 +/- 19 versus 120 +/- 34 cells/mm2, P < 0.05; arterioles: 9 +/- 4 versus 52 +/- 7 cells/mm2, P < 0.01) 30 minutes after intravenous injection of oxLDL (4 mg/kg body weight; means +/- SD of n = 7 hamsters per group). Butanol and PTX also significantly reduced the upregulation of CD11b/CD18 by f-methionyl-leucyl-phenylalanine (fMLP) and platelet-activating factor (PAF) but not by phorbol myristate acetate (PMA). Whereas fMLP and PAF stimulate leukocytes via binding to specific cell surface receptors and triggering complex signal transduction pathways, PMA bypasses these pathways and directly activates intracellular protein kinase C. By analogy, we propose that oxLDL upregulates CD11b/CD18 through its previously documented ability to stimulate the generation of second messengers. The effect of n-butanol and PTX on receptor presentation cannot be explained by changes in plasma membrane fluidity, as both agents failed to reverse the decrease in plasma membrane fluidity of neutrophils after stimulation with oxLDL, as assessed by fluorescence anisotropy measurement of the membrane marker diphenylhexatriene. Incubation of isolated neutrophils but not of whole blood with oxLDL resulted in a significant loss of L-selectin from the neutrophil surface (anti-TQ-1 binding: 40 +/- 13% of baseline, P < 0.01). A significant loss of this adhesion receptor on neutrophils and monocytes was also observed after stimulation of isolated neutrophils and whole blood with fMLP, PAF, and PMA.(ABSTRACT TRUNCATED AT 400 WORDS)

1-Butanol↗
PubMed1993

Evidence from comparative investigations that impaired platelet activation is not specific for stroke-prone spontaneously hypertensive rats.

BACKGROUND AND PURPOSE: Platelet behavior of Sprague Dawley (SD), Wistar (WI), Wistar-Kyoto (WKY), spontaneously hypertensive (SHR), and stroke-prone spontaneously hypertensive rats (SHRSP) was studied in vivo to evaluate the importance of hypertension-related hemostatic disorders. METHODS: The study was based on the model of stimulus-induced pulmonary microembolization of labeled platelets. After injection of 51Cr-labeled homologous platelets into urethane-anesthetized rats, the organ distribution of the platelets was continuously monitored by gamma detectors. Count rates of two detectors--one placed above the animals' thoraxes (C1), the other above their abdomens (C2)-and the ratio of C1:C2 were calculated. The following platelet activators were applied intravenously: adenosine diphosphate (ADP; 50 micrograms/kg), collagen (100 micrograms/kg), and thrombin (50 IU/kg). RESULTS: All three substances caused a reversible pulmonary accumulation of the labeled platelets and hence an increase in C1/C2 (delta C1/C2%). ADP induced a shift of 75% in SD, 52% in WI, 32% in WKY, 30% in SHR, and 31% in SHRSP. Thrombin-mediated shift was 79% in SD, 64% in WI, 58% in WKY, 48% in SHR, and 54% in SHRSP. Collagen induced a shift of 85% in SD, 96% in WI, 84% in WKY, 56% in SHR, and 62% in SHRSP. CONCLUSIONS: Because indistinguishable results were observed in both hypertensive strains, we conclude that impaired platelet aggregation is not specific for SHRSP. Hence, it may not primarily be responsible for the increased occurrence of stroke in these animals.

Adenosine Diphosphate↗
PubMed1991

Effects of platelet activating factor on rat platelets in vivo.

Platelet activating factor (PAF) is not able to aggregate rat platelets in vitro. Due to the agonist effects of PAF on multiple cells, a possible role of PAF in the activation of rat platelets in vivo where different cells may influence each other was investigated. The pulmonary microembolization of 51Cr-labelled activated platelets was used as in vivo model. This model allowed us to monitor platelet behaviour by means of non-invasive methods. In contrast to results obtained in vitro, PAF activated rat platelets in vivo. The pulmonary microembolization of the platelets was dose-dependent and rapidly reversible. About 0.5 microgram/kg PAF caused a half-maximal rise of platelet-bound radioactivity in the thorax. Activation of the platelets by PAF was followed by extreme desensitization, so that a second injection of PAF did not provoke a significant response of the platelets. Platelet function was, however, not completely impaired because they still accumulated in the thorax after the application of ADP (50 micrograms/kg). That pulmonary entrapment had taken place was shown by a 3-fold increase in lung specific radioactivity. This was accompanied by a short-lasting thrombocytopenia. The PAF antagonist, WEB 2170 (30 micrograms/kg), significantly inhibited the microembolization of the platelets induced by PAF. Under in vitro conditions leukocytes purified from rat blood and activated by PAF were able to induce platelet aggregation. These results demonstrate that a PAF-specific activation of rat platelets is achievable in vivo which is probably mediated by other cells.

Adenosine Diphosphate↗
PubMed1991

Evaluation of pulmonary accumulation of 51chromium-labelled rat platelets following intravenous application of ADP and collagen.

We examined the effects of ADP- and collagen-induced pulmonary platelet embolism in the rat. Homologous 51Chromium-labelled platelets were used to monitor extracorporally the distribution of platelets in the circulation. For that purpose, collimated iodide scintillation detectors were placed above thorax (C1) and abdomen (C2). A dose-dependent increase in thoracic radioactivity, paralleled by a decrease in the abdomen, was observed after intravenous injection of ADP and collagen. This resulted in a shift of C1/C2, so that the effect of collagen was more pronounced (maximal increase of C1/C2 = 134%) than ADP (maximal increase of C1/C2 = 79%). The increase in thoracic radioactivity was caused by the uptake of platelets in the lung as was shown after administration of collagen (6-fold enrichment of labelled platelets). Lung platelet sequestration resulted in a dose-dependent thrombocytopenia. The ADP -and collagen-induced pulmonary platelet embolism reversibly provoked cardiovascular symptoms of shock: hypotension and bradycardia. Impaired gas exchange during platelet accumulation manifested itself in a reversible arterial hypoxaemia and hypercapnia, followed by a weak acidosis. We were able to inhibit ADP-dependent thoracic platelet accumulation by ticlopidine in a dose-related manner as well as collagen-induced thoracic platelet accumulation by acetylsalicylic acid. The results indicate that behaviour of homologous labelled rat platelets in vivo can easily be monitored, thus offering the opportunity to investigate the effects of antiaggregatory drugs on platelets in their natural environment.

Adenosine Diphosphate↗
PubMed1991

In-vivo antithrombotic potency of placenta protein 4 (annexin V).

The antithrombotic properties of Placenta Protein 4 (PP4) were investigated in laser or photochemically induced thrombus formation models in rats. In both in-vivo test-systems PP4 displayed a significant antithrombotic effect at dose levels as low as 0.3 and 1.0 mg/kg body weight. Bleeding times, surprisingly, were not prolonged significantly at these dose regimens. Maximal inhibition of thrombus formation in the laser-model was observed 15 min after intravenous administration of PP4, but was not recognizable in a clear-cut reaction in the second model. Determination of PP4 plasma levels in two monkeys revealed a half-life of 11.5 and 14.9 min, respectively. The maximal anticoagulant effect was observed between 15 and 30 min after administration of PP4 as determined functionally by means of thrombelastography.

Animals↗
PubMed1991

Antithrombotic effects of recombinant hirudin in different animal models.

The effect of recombinant hirudin (r-hirudin; HBW 023) was studied in four different models of thrombosis as well as on bleeding time. Arteriolar thrombus formation was induced in rats either by argon laser injury or by photochemical reaction. r-Hirudin, given by intravenous infusion, significantly inhibited arteriolar thrombus formation and arterial bleeding time at a dose of 40 micrograms/kg.min. In rabbit jugular veins and carotid arteries, occluding thrombi were produced by stenosis and endothelial damage. r-Hirudin reduced the incidence of thrombosis dose dependently (ED50 0.7 and 1.0 mg/kg i.v. in arteries and veins, respectively). Caval vein thrombosis was initiated in rats by insertion of a stainless steel coil. This thrombosis was dose dependently reduced by the injection of r-hirudin (ED50 0.16 mg/kg i.v.). The duration of the antithrombotic effect of 0.25 mg/kg of r-hirudin in caval veins was about 60 min, whereas the arterial bleeding time was significantly prolonged in these rats for only 20 min. The plasma level of r-hirudin had dropped to 0.12 micrograms/ml 60 min after injection. These results suggest that the duration of the effect on bleeding time may be shorter than the antithrombotic action of r-hirudin.

Animals↗
PubMed1991

Leukocyte counts and activation in spontaneously hypertensive and normotensive rats.

The etiology for the progressive organ injury in hypertension is largely speculative. Recent studies have shown that leukocytes play a key role in several cardiovascular diseases. As an initial step toward investigating the role of leukocytes in hypertension, we measured leukocyte counts and spontaneous activation of granulocytes of freshly drawn unseparated blood samples in spontaneously hypertensive rats and in their normotensive counterpart, Wistar-Kyoto rats. The animals were derived from one breeder in the United States and from two breeders in Europe. Total leukocyte counts in young, mature, and old hypertensive rats were 50-100% above the controls. The number of granulocytes in mature and old spontaneously hypertensive rats in more than 100% elevated compared with control rats. In young hypertensive rats the mean granulocyte count was only slightly elevated. The number of spontaneously activated granulocytes, as detected by the nitroblue tetrazolium reduction, increases with age in both species; in mature spontaneously hypertensive rats, it is more than 300% above the values in the controls. Furthermore, in mature hypertensive rats the number of monocytes, activated monocytes, and the lymphocyte count are also significantly elevated over the values in the normotensive controls. It is proposed that these elevated leukocyte counts may constitute an enhanced risk for organ injury in the spontaneously hypertensive rat.

Animals↗