Effect of NO on EDHF response in rat middle cerebral arteries

• Published in: American journal of physiology. Heart and circulatory physiology 2002-02, Vol.282 (2), p.H734-H738
• Main Authors: Schildmeyer, Lisa A, Bryan, Robert M., Jr
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphate - analogs & derivatives; Adenosine Triphosphate - pharmacology; Animals; Biological Factors - pharmacology; Cyclic GMP - metabolism; Cyclooxygenase Inhibitors - pharmacology; Dose-Response Relationship, Drug; Enzyme Inhibitors - pharmacology; Indomethacin - pharmacology; Male; Middle Cerebral Artery - drug effects; Middle Cerebral Artery - physiology; NG-Nitroarginine Methyl Ester - pharmacology; Nitric Oxide - metabolism; Nitric Oxide Donors - pharmacology; Oxadiazoles - pharmacology; Penicillamine - analogs & derivatives; Penicillamine - pharmacology; Quinoxalines - pharmacology; Rats; Rats, Long-Evans; Thionucleotides - pharmacology; Vasodilation - drug effects
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.00583.2001

Departments of 1  Anesthesiology, Molecular Physiology, and 2  Biophysics, and 3  Section of Cardiovascular Sciences, Department of Medicine Baylor College of Medicine, Houston, Texas 77030 Whereas the actual identity of endothelium-derived hyperpolarizing factor (EDHF) is still not certain, it involves a process requiring the endothelium and eliciting hyperpolarization and relaxation of smooth muscle. It is neither nitric oxide (NO) nor prostacyclin, and its presence has been demonstrated in a variety of vessels. Recent studies in peripheral vessels report that EDHF-mediated dilations were either attenuated or blocked by NO. Studies presented here demonstrate that NO does not block EDHF-mediated dilations in cerebral vessels. Rat middle cerebral arteries were cannulated, pressurized, and luminally perfused. EDHF-mediated dilations were elicited by the luminal application of ATP in the presence of N G -nitro- L -arginine methyl ester ( L -NAME) and indomethacin (inhibitors of NO synthase and cyclooxygenase, respectively). These dilations persisted when S -nitroso- N -acetylpenicillamine, an NO donor, was added exogenously in the presence of L -NAME, or when endogenous NO was present but its cGMP actions were blocked by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, an inhibitor of guanylate cyclase. These findings demonstrate that the EDHF response is not suppressed by NO in cerebral vessels and suggests a role for EDHF during normal physiological conditions. nitric oxide; endothelium-derived hyperpolarizing factor; guanosine 3',5'-cyclic monophosphate