Changes of sequestered leukocytes and platelets by inhalation prostaglandin E(1) in the pulmonary microvasculature of rats with monocrotaline-induced pulmonary hypertension.
The role of leukocytes (WBCs) and platelets (PLTs) in the pulmonary circulation may be important in the development of monocrotaline (MCT)-induced pulmonary hypertension in rats. We investigated the suppressive effects of long-term prostaglandin E(1) (PGE(1)) aerosol on the changes in WBCs and PLTs in the peripheral blood and the pulmonary microvasculature during the development of chronic pulmonary hypertension in MCT rats by real-time confocal scanning laser microscopy. The number of WBCs and PLTs in peripheral blood did not significantly change by inhalation of PGE(1). The number of WBCs and PLTs sequestered in the pulmonary microvasculature of rats subjected PGE(1) inhalation immediately after MCT injection rats with (MCT plus PGE(1) inhalation) significantly decreased from 1 to 4 weeks compared to rats not subjected to PGE(1) inhalation (p < 0.01). The pulmonary systolic arterial pressure and the weight ratio of the right ventricle to the intraventricular septum plus the left ventricle (RV/IVS + LV weight ratio or RV weight ratio) in rats with MCT plus PGE(1) inhalation significantly decreased compared to rats not subjected to PGE(1) inhalation (p < 0.01). The levels of peripheral CD62L-positive WBCs in rats with MCT plus PGE(1) inhalation significantly decreased from 1 to 2 weeks compared to rats not subjected to PGE(1) inhalation, but the levels of peripheral CD18 and CD49d-positive WBCs did not significantly change. We conclude that long-term inhalation of PGE(1) is a very useful therapy in chronic pulmonary hypertension, and the mechanism of suppressing pulmonary hypertension is associated with suppressive effects on sequestered WBCs, especially CD62-positive WBCs and PLTs in the pulmonary microvasculature.
Kato
Shiro
S
Department of Cardiology and Pneumology, Dokkyo University School of Medicine, Tochigi, Japan.
Kishiro
Izumi
I
Sugimura
Hiroyuki
H
Machida
Suguru
S
Fuse
Daisuke
D
Kaneko
Noboru
N
D000280:Administration, Inhalation; D000527:Alprostadil / Q000008:administration & dosage*; D000818:Animals; D001792:Blood Platelets / Q000473:pathology*; D001794:Blood Pressure / Q000187:drug effects; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000473:pathology*; D019041:L-Selectin / Q000032:analysis; D007958:Leukocyte Count; D007962:Leukocytes / Q000737:chemistry / Q000473:pathology*; D008168:Lung / Q000098:blood supply*; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000473:pathology*; D016686:Monocrotaline; D010976:Platelet Count; D051381:Rats; D017207:Rats, Sprague-Dawley
D019041:L-Selectin; D016686:Monocrotaline; D000527:Alprostadil