TY - JOUR
T1 - Nitric oxide and prostacyclin influence coronary vasomotor tone in perfused rabbit heart and modulate endothelin-1 activity
AU - Berti, F.
AU - Rossoni, G.
AU - Delia Bella, D.
AU - Villa, L. M.
AU - Buschi, A.
AU - Trento, F.
AU - Berti, M.
AU - Tondo, C.
PY - 1993
Y1 - 1993
N2 - Using isolated perfused rabbit heart electrically paced, we assessed the relevance of both nitric oxide (NO) and prostacyclin (PGI2) in regulation of resting coronary perfusion pressure (CPP). In preparations in which NO-synthase was inhibited by NG-monomethyl-L-arginine (L-NMMA, 10 μM), resting CPP increased significantly; this phenomenon was potentiated by indomethacin infusion (3 μM), prevented by L-arginine (100 μM) and significantly reduced by iloprost (55 nM) and defibrotide (200 μg/ml). Furthermore, the increase in resting CPP induced by graded doses of endothelin-1 (ET-1 0.6-160 pmol), was further augmented by blocking of prostaglandin biosynthesis with indomethacin (3 μM) and was substantially reduced when the rate of formation of PGI2 was enhanced by defibrotide (200 μg/ml). Moreover, the coronary vasoconstriction induced by ET-1 (2, 4, and 8 pmol) was increased in hearts in which NO-synthase was blocked by L-NMMA (10 μM) and this event was abolished in preparations in which PGI2 synthesis was stimulated by defibrotide (200 μg/ml). These results further emphasize that rabbit coronary vessels are continuously dilated by NO released from endothelial cells. They also indicate that PGI2 takes part in NO generation in the endothelial-derived relaxing mechanism. Inactivation of this mechanism, owing to decreased formation of NO and PGI2 in rabbit heart, induces hyperreactivity of coronary smooth muscles to ET-1. Finally, an increase in PGI2 production (such as that caused by defibrotide) may counterbalance impaired NO generation and attenuate hyperreactivity of the coronary vasculature.
AB - Using isolated perfused rabbit heart electrically paced, we assessed the relevance of both nitric oxide (NO) and prostacyclin (PGI2) in regulation of resting coronary perfusion pressure (CPP). In preparations in which NO-synthase was inhibited by NG-monomethyl-L-arginine (L-NMMA, 10 μM), resting CPP increased significantly; this phenomenon was potentiated by indomethacin infusion (3 μM), prevented by L-arginine (100 μM) and significantly reduced by iloprost (55 nM) and defibrotide (200 μg/ml). Furthermore, the increase in resting CPP induced by graded doses of endothelin-1 (ET-1 0.6-160 pmol), was further augmented by blocking of prostaglandin biosynthesis with indomethacin (3 μM) and was substantially reduced when the rate of formation of PGI2 was enhanced by defibrotide (200 μg/ml). Moreover, the coronary vasoconstriction induced by ET-1 (2, 4, and 8 pmol) was increased in hearts in which NO-synthase was blocked by L-NMMA (10 μM) and this event was abolished in preparations in which PGI2 synthesis was stimulated by defibrotide (200 μg/ml). These results further emphasize that rabbit coronary vessels are continuously dilated by NO released from endothelial cells. They also indicate that PGI2 takes part in NO generation in the endothelial-derived relaxing mechanism. Inactivation of this mechanism, owing to decreased formation of NO and PGI2 in rabbit heart, induces hyperreactivity of coronary smooth muscles to ET-1. Finally, an increase in PGI2 production (such as that caused by defibrotide) may counterbalance impaired NO generation and attenuate hyperreactivity of the coronary vasculature.
KW - Coronary tone
KW - Defibrotide
KW - Endothelin-1
KW - Nitric oxide
KW - Prostacyclin
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UR - http://www.scopus.com/inward/citedby.url?scp=0027163667&partnerID=8YFLogxK
M3 - Article
C2 - 7692176
AN - SCOPUS:0027163667
VL - 22
SP - 321
EP - 326
JO - Journal of Cardiovascular Pharmacology
JF - Journal of Cardiovascular Pharmacology
SN - 0160-2446
IS - 2
ER -