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 E1 (PGE1) 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 PGE1. The number of WBCs and PLTs sequestered in the pulmonary microvasculature of rats subjected PGE1 inhalation immediately after MCT injection rats with (MCT plus PGE1 inhalation) significantly decreased from 1 to 4 weeks compared to rats not subjected to PGE1 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 PGE1 inhalation significantly decreased compared to rats not subjected to PGE1 inhalation (p < 0.01). The levels of peripheral CD62L-positive WBCs in rats with MCT plus PGE1 inhalation significantly decreased from 1 to 2 weeks compared to rats not subjected to PGE1 inhalation, but the levels of peripheral CD18 and CD49d-positive WBCs did not significantly change. We conclude that long-term inhalation of PGE1 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.

Keywords:
Pulmonary hypertension, Prostaglandin E1, Leukocytes, Platelets
1.
Jensen NK, Lundin S, Riksten SE: Vasodilation therapy after heart transplantation: Effects of inhaled nitric oxide and intravenous prostacyclin, prostaglandin E1, and sodium nitroprusside. J Heart Lung Transplant 1995;14:436–438.
2.
McLean RF, Prielipp RC, Roenthal MH, Pearl RG: Vasodilator therapy in microembolic porcine pulmonary hypertension. Anesth Analg 1990;71:35–41.
3.
Bolliger C, Fourie P, Coetzee A: The effect of prostaglandin E1 on acute pulmonary artery hypertension during oleic acid-induced respiratory dysfunction. Chest 1991;99:1501–1506.
4.
Fisher CA, Kappa JR, Sinha AK, Cottrell ED, Reiser HJ, Addonzio VP: Comparison of equimolar concentrations of iloprost, prostacyclin, and prostaglandin E1 on human platelet function. J Lab Clin Med 1987;109:184–190.
5.
Humbert M, Sanchez O, Fartoukh M, Jagot JL, Sitbon O, Simonneau G: Treatment of severe pulmonary hypertension secondary to connective tissue disease with continuous IV epoprostenol (prostacyclin). Chest 1998;114:80S–82S.
6.
Higenbottam TW, Butt AY, Dinh-Xaun AT, Takao M, Cremona G, Akamine S: Treatment of pulmonary hypertension with the continuous infusion of a prostacyclin analogue, iloprost. Heart 1998;79:175–179.
7.
McLaughlin VV, Genthner DE, Panella MM, Hess DM, Rich S: Compassionate use of continuous prostacyclin in the management of secondary pulmonary hypertension: A case series. Ann Intern Med 1999;130:740–743.
8.
Walmrath D, Schermuly R, Pilch J, Grimminger F, Seeger W: Effect of inhaled versus intravenous vasodilators in experimental pulmonary hypertension. Eur Respir J 1997;10:1084–1092.
9.
Olschewski H, Walmrath D, Schermuly R, Ghofrani A, Grimminger F, Seeger W: Aerosolized prostacyclin, iloprost in severe pulmonary hypertension. Ann Intern Med 1996;124:820–824.
10.
Walmrath D, Schneider T, Pilch J, Schermuly R, Grimminger F, Seeger W: Effects of aerosolized prostacyclin in severe pneumonia: Impact of fibrosis. Am J Respir Crit Care Med 1995;151:724–730.
11.
Cirillo P, Golino P, Ragni M, Battaglia C, Pacifico F, Formisano S, Buono C, Conodrelli M, Chiariello M: Activated platelets and leukocytes cooperatively stimulated smooth muscle cell proliferation and proto-oncogene expression via release of soluble growth factors. Cardiovasc Res 1999;43:210–218.
12.
Yi ES, Lee H, Yin S, Piguet P, Sarosi I, Kaufmann S, Tarpley J, Wang NS, Ulich TR: Platelet-derived growth factor causes pulmonary cell proliferation and collagen deposition in vivo. Am J Pathol 1996;149:539–548.
13.
Zhung P, Summer WR, Baghy GJ, Nelson S: Innate immunity and pulmonary host defense. Immunol Rev 2000;173:39–51.
14.
Kato S, Ohnuma N, Ohno K, Takasaki K, Okamoto S, Asai T, Okuda M, Nakamoto T, Izuka M: Changes in sequestered leukocytes and platelets in the pulmonary microvasculature of rats with monocrotaline-induced pulmonary hypertension. Int J Microcirc 1997;17:290–297.
15.
Mitauchi T, Yorikane R, Sakai S, Sakurai T, Okada M, Nishikibe M, Yano M, Yamaguchi I, Sugishita Y, Goto K: Contribution of endogenous endothelin-1 to the progression of cardiopulmonary alterations in rats with monocrotaline-induced pulmonary hypertension. Circ Res 1993;73:887–897.
16.
Fulton RM, Hutchinson EC, Jones AM: Ventricular weight in cardiac hypertrophy. Br Heart J 1952;14:413–420.
17.
Scott JP, Higenbottam T, Wallwork J: The acute effect of the synthetic prostacyclin analogue iloprost in primary pulmonary hypertension. Br J Clin Pharmacol 1990;6:231–234.
18.
De la Mata JJ, Gomez-Sanches MZ, Aranzana M, Gomez-Reino JJ. Long-term iloprost infusion therapy for severe pulmonary hypertension in patients with connective tissue disease. Arthritis Rheum 1994;37:1528–1533.
19.
Sakuma F, Miyata M, Kasukawa R: Suppressive effect of prostaglandin E1 on pulmonary hypertension induced by monocrotaline in rats. Lung 1999;177:77–78.
20.
Tamura DY, Moore EE, Partrick DA, Johnson JL, Offner PJ, Sillman CC: Prostaglandin E1 attenuates cytotoxic mechanisms of primed neutrophils. Shock 1998;9:171–176.
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2002
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