title: Inhibition of nitric oxide synthesis augments centrally induced sympathetic coronary vasoconstriction in cats.
abstract: The principal effect of sympathetic activation on the coronary circulation is an alpha-adrenergic coronary vasoconstriction in the presence of beta-receptor blockade. Secondary effects include vasodilation due to beta-adrenoceptor stimulation and alpha 2-mediated release of endothelium-derived relaxing factor (EDRF) from the coronary vascular endothelium. We hypothesized that blockade of nitric oxide synthesis (nitro-L-arginine methyl ester, L-NAME) would augment coronary vasoconstriction to sympathetic stimulation as a result of a decrease in alpha 2-mediated EDRF release. In chloralose-anesthetized cats, hypothalamic stimulation produced increases in coronary vascular resistance [maximum 26 +/- 9% (SE)] and arterial pressure (41 +/- 7%) and a decrease in coronary blood flow velocity (15 +/- 6%). L-NAME (3 mg/kg iv) increased baseline arterial pressure from 69 +/- to 92 +/- 7 mmHg (P < 0.05). After L-NAME, a greater increase in coronary vascular resistance (55 +/- 20%, P < 0.05), a decrease in coronary blood flow velocity (24 +/- 7%, P < 0.05), and a similar pressor response (34 +/- 7%) were observed in response to hypothalamic stimulation. L-Arginine reversed the effect of L-NAME on coronary vasoconstriction to hypothalamic stimulation. Similar increases in arterial pressure (from 73 +/- 3 to 91 +/- 5 mmHg, P < 0.05) with vasopressin (0.01-0.05 U/min) failed to enhance coronary vasoconstriction to activation in anterior hypothalamus. We conclude that inhibition of EDRF synthesis augments centrally induced sympathetic coronary vasoconstriction in the cat.
authors.affiliation: Veterans Administration Medical Center, Iowa City, Iowa.
authors.forename: A R
authors.initials: AR
authors.lastname: Goodson
authors.forename: J M
authors.initials: JM
authors.lastname: Leibold
authors.forename: D D
authors.initials: DD
authors.lastname: Gutterman
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002415:Cats; D003331:Coronary Vessels / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D004558:Electric Stimulation; D005260:Female; D007031:Hypothalamus / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects; D014667:Vasopressins / Q000494:pharmacology*; D014682:Vena Cava, Inferior / Q000502:physiology
chemical_list: D014667:Vasopressins; D009569:Nitric Oxide; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester