Protective action of prostaglandin E1 (PGE1) against constrictor mediators in isolated rat heart and lung.
Prostaglandin (PG) E1 (2.8 to 280 nmol/L) dose-dependently inhibited the platelet-activating factor (PAF)-induced increase in coronary perfusion pressure (CPP) in isolated constant flow perfused rat hearts. The PAF-induced release of immunoreactive leukotrienes (iLT) and thromboxane B2 (iTxB2) in isolated rat hearts was also attenuated. PAF induced a significant decrease in left ventricular cAMP content, which was antagonized by PGE1. PGE1 also decreased the production of iLT, but not of iTxB2, in A23187-stimulated minced rat lung tissue. Furthermore, PGE1 inhibited the increase in CPP induced by LTD4 and arginine vasopressin (AVP) in the isolated perfused rat heart. The inhibitory effects of PGE1 on coronary vasoconstrictor substances were not due to a nonspecific vasodilator effect since sodium nitroprusside neither inhibited the increase in CPP nor the release of eicosanoids induced by PAF. Moreover, PGE1 did not inhibit the PAF-induced hypotension in vivo, indicating that PGE1 is not a PAF receptor antagonist. These results suggest that PGE1 may exert an important regulatory effect on coronary vascular homeostasis by stimulation of cyclic AMP and may be important in controlling eicosanoid metabolism in the rat heart. Furthermore, beneficial effects of PGE1 in circulatory shock and myocardial ischemia may be related to this inhibitory effect of PGE1.
Terashita
Z
Z
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107.
Stahl
G L
GL
Lefer
A M
AM
D000527:Alprostadil / Q000494:pharmacology*; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects*; D000242:Cyclic AMP / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010477:Perfusion; D010972:Platelet Activating Factor / Q000494:pharmacology*; D011453:Prostaglandins / Q000096:biosynthesis*; D011652:Pulmonary Circulation / Q000187:drug effects*; D051381:Rats; D014655:Vascular Resistance / Q000187:drug effects*
D010972:Platelet Activating Factor; D011453:Prostaglandins; D001127:Arginine Vasopressin; D009599:Nitroprusside; D000242:Cyclic AMP; D000527:Alprostadil