title: Nitric oxide bioavailability affects cardiovascular regulation dependent on cardiac nerve status.
abstract: The sympathetic nervous system and nitric oxide (NO) contribute to regulation of vascular tone, blood flow regulation and cardiac function. Intrinsic cardiac neurons are tonically influenced by locally released NO and exogenous NO donors; however, the role of intact central neural connections remains controversial. We investigated the effects of S-nitroso-N-acetylpenicillamine (SNAP) administered into an intracoronary artery near the ventral interventricular ganglionated plexus (VIVGP) to evaluate distribution of myocardial blood flow (MBF) and ventricular function in normal and acute cardiac decentralized dogs. MBF was measured with microspheres during infusion of SNAP (100μM, IC) after systemic administration of 7-nitroindazole (nNOS blocker) followed by N(ω)-nitro-L-arginine methyl ester (LN; non-selective NOS blocker). Cardiac dynamics were not significantly affected by cardiac decentralization; several of these parameters (aortic systolic and diastolic pressures) were significantly increased after systemic administration of LN. Overall SNAP administered to the VIVGP increased blood flow in the anterior LV wall (vs. posterior LV wall) without affecting other cardiodynamic factors. In cardiac decentralized dogs subepicardial blood flow to the anterior LV wall during LN+SNAP was diminished resulting in a significantly higher inner:outer blood flow ratio (index of blood flow uniformity across the LV wall). LV function was not affected by acute cardiac decentralization; however, LV ejection fraction decreased markedly after LN (reduced NO bioavailability). These results validate earlier claims that reduced NO bioavailability imposes an upper limit on myocardial blood flow regulation and its transmural distribution. These effects are exacerbated after disconnection of intrinsic cardiac neurons from intact central neuron connections.
authors.affiliation: Faculty of Medicine, Laval University, Cité universitaire, Sainte-Foy (Qc), G1K 7P4, Canada. Electronic address: john.kingma@fmed.ulaval.ca.
authors.forename: J G
authors.initials: JG
authors.lastname: Kingma
authors.affiliation: Faculty of Medicine, Laval University, Cité universitaire, Sainte-Foy (Qc), G1K 7P4, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Simard
authors.affiliation: Faculty of Medicine, Laval University, Cité universitaire, Sainte-Foy (Qc), G1K 7P4, Canada.
authors.forename: J R
authors.initials: JR
authors.lastname: Rouleau
mesh_terms: D000818:Animals; D017763:Autonomic Denervation; D001682:Biological Availability; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D006352:Heart Ventricles / Q000187:drug effects; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000201:enzymology; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000494:pharmacology; D010101:Oxygen Consumption; D012039:Regional Blood Flow / Q000187:drug effects; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology; D016276:Ventricular Function / Q000187:drug effects
chemical_list: D004791:Enzyme Inhibitors; D007191:Indazoles; D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D019001:Nitric Oxide Synthase; C080122:7-nitroindazole
keywords: Acute cardiac decentralization; Intrinsic cardiac neurons; Myocardial blood flow; Nitric oxide donor; Nitric oxide synthase isoforms