Macrophage activation and leukocyte adhesion after liver transplantation

1993 ◽  
Vol 265 (1) ◽  
pp. G172-G177 ◽  
Author(s):  
I. Marzi ◽  
F. Walcher ◽  
V. Buhren
Keyword(s):  
Liver Transplantation ◽  
Calcium Channel ◽  
Calcium Channel Blocker ◽  
Kupffer Cell ◽  
Kupffer Cells ◽  
Cell Activation ◽  
Channel Blocker ◽  
Leukocyte Adhesion ◽  
Cell Activity ◽  
Phagocytic Cells

Reperfusion injury involving oxygen radicals, leukocyte adhesion, and Kupffer cell activation has been suggested to contribute to the failure of transplanted livers. The aim of this study was to evaluate Kupffer cell activity, leukocyte adhesion, and the effect of the calcium channel blocker nisoldipine after rat liver transplantation by means of in vivo fluorescence microscopy to further investigate the mechanism of graft failure. Inclusion of 1.4 microM nisoldipine to the University of Wisconsin cold storage solution (UW) did not improve sinusoidal perfusion and vasoconstriction after transplantation compared with UW alone (82.7 +/- 1.0% vs. 79.2 +/- 1.7% perfused sinusoids; 7.3 +/- 0.1 vs. 8.0 +/- 0.2 microns diam of sinusoids; means +/- SE). Permanent as well as temporary adhesion of leukocytes rose from 9.4 +/- 0.8 and 10.2 +/- 0.5% in sham-operated controls to 19.1 +/- 2.2 and 19.2 +/- 0.5% after liver transplantation, respectively. Inclusion of the calcium channel blocker reduced permanent (9.1 +/- 0.8%; P < 0.05) and temporary adherent leukocytes (11.3 +/- 1.0%; P < 0.05). Phagocytosis of latex beads by Kupffer cells or other phagocytic cells as a function of activity rose after transplantation (e.g., periportal area: 509 +/- 44/mm2) compared with controls (316 +/- 22/mm2). This was significantly reduced by inclusion of nisoldipine to UW (322 +/- 32/mm2). The results of this study demonstrate activation of Kupffer cells and increase of leukocyte adhesion to the sinusoidal endothelial wall during reperfusion of transplanted livers. A calcium-dependent release of mediators by Kupffer cells that promote leukocyte adhesion is suggested as an underlying mechanism.

Chronic treatment by the calcium channel blocker ± PN 200-110 in the rat counteracts the stimulations of pituitary weight, prolactin release and pituitary C-kinase activity induced by a chronic estradiol treatment, in vivo

1990 ◽  
Vol 122 (3) ◽  
pp. 403-408
Author(s):  
Ph. Touraine ◽  
P. Birman ◽  
F. Bai-Grenier ◽  
C. Dubray ◽  
F. Peillon ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Calcium Channel ◽  
Calcium Channel Blocker ◽  
Channel Blocker ◽  
Plasma Prolactin ◽  
Estradiol Treatment ◽  
Kinase C ◽  
Protein Kinase C Activity

Abstract In order to investigate whether a calcium channel blocker could modulate the protein kinase C activity in normal and estradiol pretreated rat pituitary, female Wistar rats were treated or not (controls) with ± PN 200-110 (3 mg · kg−1 · day−1, sc) for 8 days or with estradiol cervical implants for 8 or 15 days, alone or in combination with PN 200-110 the last 8 days. Estradiol treatment induced a significant increase in plasma prolactin levels and pituitary weight. PN 200-110 administered to normal rats did not modify these parameters, whereas it reduced the effects of the 15 days estradiol treatment on prolactin levels (53.1 ± 4.9 vs 95.0 ±9.1 μg/l, p<0.0001) and pituitary weight (19.9 ± 0.4 vs 23.0 ± 0.6 mg, p <0.001), to values statistically comparable to those measured after 8 days of estradiol treatment. PN 200-110 alone did not induce any change in protein kinase C activity as compared with controls. In contrast, PN 200-110 treatment significantly counteracted the large increase in soluble activity and the decrease in the particulate one induced by estradiol between day 8 and day 15. We conclude that PN 200-110 opposed the stimulatory effects of chronic in vivo estradiol treatment on plasma prolactin levels and pituitary weight and that this regulation was related to a concomitant modulation of the protein kinase C activity.

Effects of an Antihypertensive Combination in Japanese Hypertensive Outpatients Based on the Long-Acting Calcium Channel Blocker Benidipine on Vascular and Renal Events: A Sub-Analysis of the COPE Trial

2020 ◽  
Vol 16 ◽  
Author(s):  
Seiji Umemoto ◽  
Toshio Ogihara ◽  
Masunori Matsuzaki ◽  
Hiromi Rakugi ◽  
Kazuyuki Shimada ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Calcium Channel ◽  
Calcium Channel Blocker ◽  
Channel Blocker ◽  
Rank Test ◽  
Vascular Events ◽  
Treatment Groups ◽  
Β Blocker ◽  
The Difference ◽  
Long Acting

Background: In the trial known as COPE (Combination Therapy of Hypertension to Prevent Cardiovascular Events) three benidipine (a calcium channel blocker; CCB) regimens were compared. Hypertensive Japanese outpatients aged 40–85 years (n=3,293) who did not achieve the target blood pressure of <140/90 mmHg with benidipine 4 mg/day were treated with the diuretic thiazide (n=1,094) or a β-blocker (n=1,089) or an additional angiotensin receptor blocker (ARB; n=1,110). A significantly higher incidence of hard cardiovascular composite endpoints and of fatal or non-fatal strokes was observed in the benidipine-β-blocker group compared to the benidipine-thiazide group. Objective and Methods: We further evaluated the treatment effects of the three benidipine-based regimens on vascular and renal events in a sub-analysis of the COPE patients. Results: A total of 10 vascular events (0.8 per 1,000 person-years) including one aortic dissection (0.1 per 1,000 person-years) and nine cases of peripheral artery disease (0.8 per 1,000 person-years) were documented, as was a total of seven renal events (0.6 per 1,000 person-years). No significant differences in vascular and renal events were revealed among the three treatment groups: vascular events p=0.92 renal events p=0.16 log-rank test. Conclusions: Blood pressure-lowering therapy with benidipine combined with an ARB, β-blocker, or thiazide was similarly effective in the prevention of vascular and renal events in hypertensive outpatients, although there is no enough these events to compare the difference in the three treatment groups.

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