Neuropeptide Y and coronary vasoconstriction: role of thromboxane A2.
We previously reported that coronary constriction following neuropeptide Y (NPY) was alleviated by cyclooxygenase blockade. To determine the role of thromboxane A2 (TxA2), anesthetized dogs received two paired doses of NPY given 2 h apart. Nine control dogs received NPY alone. Nine test dogs received one of three TxA2 receptor antagonists given between the doses of NPY. Also, five dogs received NPY during which prostaglandins were measured. In controls, NPY decreased coronary blood flow and increased aortic pressure; coronary resistance was increased significantly. Heart rate fell, and myocardial oxygen consumption was unchanged. Thromboxane receptor blockers significantly relieved the coronary constrictor effect of NPY. The reduction in coronary blood flow was blunted, while heart rate, first derivative of left ventricular pressure, and myocardial oxygen consumption were unchanged. Alleviation by TxA2 receptor blockade paralleled that reported for cyclooxygenase inhibitors. Also, significant increases in coronary venous TxA2 were seen at the time of maximal increases in coronary resistance, while prostacyclin was unchanged. In summary, TxA2 appears to mediate part of the coronary constrictor effect of NPY.
Martin
S E
SE
Carlyle Fraser Heart Center, Crawford Long Hospital, Emory University, Atlanta, Georgia.
Kuvin
J T
JT
Offenbacher
S
S
Odle
B M
BM
Patterson
R E
RE
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects*; D004285:Dogs; D005260:Female; D008297:Male; D009478:Neuropeptide Y / Q000494:pharmacology*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors; D013928:Thromboxane A2 / Q000502:physiology*; D013929:Thromboxane B2 / Q000097:blood; D014661:Vasoconstriction / Q000187:drug effects*; D014680:Veins
D009478:Neuropeptide Y; D011450:Prostaglandin Endoperoxides, Synthetic; D017482:Receptors, Thromboxane; D013929:Thromboxane B2; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid