Higher viscosity participates in the regulation of coronary flow via nitric oxide and indomethacin-sensitive contracting factor.
Few studies have reported on the association of viscosity with coronary circulation. We evaluated the change in coronary flow after dextran was added to a perfusion solution to increase viscosity in isolated rat hearts. We also measured NOx- production induced by the change in shear stress in the coronary effluent, as a marker of NO synthesis. The baseline coronary flow was not influenced by the presence of either the cyclooxygenase inhibitor indomethacin, the thromboxane A2 (TXA2)-prostaglandin H2 (PGH2) receptor antagonist ONO-3708, or the TXA2 synthase inhibitor OKY-046. After exposure to solution containing 0.5% dextran, the coronary flow first decreased and then gradually increased until 10 min. The initial decrease in coronary flow was inhibited by indomethacin, ONO-3708, and OKY-046 individually. The gradual increase was completely inhibited by the NO inhibitor L-NAME, but not by indomethacin or ONO-3708. OKY-046 partially inhibited the increase. NOx- levels in the effluent were higher after the dextran solution was administered, and the increased NOx- levels were inhibited by L-NAME. The increased NOx- levels were not inhibited by inhibitors of the cyclooxygenase pathway. It appears that a higher viscosity of perfusion solution induced a gradual increase in NO production and was associated with increased production of indomethacin-sensitive contracting factor.
Kimura
Akira
A
Department of Cardiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
Okumura
Kenji
K
Mokuno
Shinji
S
Numaguchi
Yasushi
Y
Matsui
Hideo
H
Murohara
Toyoaki
T
D000818:Animals; D001809:Blood Viscosity / Q000187:drug effects / Q000502:physiology*; D003326:Coronary Circulation / Q000502:physiology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D003911:Dextrans / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D008689:Methacrylates / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052250:Nitric Oxide Synthase Type III; D051381:Rats; D011921:Rats, Inbred WKY; D012212:Rheology; D013928:Thromboxane A2 / Q000031:analogs & derivatives* / Q000494:pharmacology
D016861:Cyclooxygenase Inhibitors; D003911:Dextrans; D004791:Enzyme Inhibitors; D008689:Methacrylates; D009569:Nitric Oxide; D013928:Thromboxane A2; C049855:ONO 3708; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; C034364:ozagrel; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin