Vagal nerve stimulation during muscarinic and beta-adrenergic blockade causes significant coronary artery dilation |
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| Affiliation: | 1. Department of Neurochemistry and Neuropharmacology, Institut d’Investigacions Biomèdiques de Barcelona (IIBB-CSIC) (IDIBAPS), Barcelona, Spain;2. Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain;3. Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain;4. Departament d׳Anatomia i Embriologia Humana, Facultat de Medicina, Universitat de València, València, Spain;1. Department of Experimental and Clinical Physiology, Laboratory of Centre for Preclinical Research, the Medical University of Warsaw, Banacha 1B, 02-097 Warsaw, Poland;2. Department of Biophysics and Physiology, the Medical University of Warsaw, Chałubińskiego 5, 02-004 Warsaw, Poland;3. Chair and Department of Experimental and Clinical Pharmacology, Laboratory of Centre for Preclinical Research, the Medical University of Warsaw, Banacha 1B, 02-097 Warsaw, Poland;1. Obesity Unit, Hospital Clinic Universitari, Barcelona, Spain;2. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain;3. Institut d’Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Barcelona, Spain;1. Department of Pharmacology, Osaka City University Medical School, Osaka 545-8585, Japan;2. Applied Pharmacology and Therapeutics, Osaka City University Medical School, Osaka 545-8585, Japan;1. Neurobiology of Social Behavior Laboratory, Department of Psychology, Boston College, Chestnut Hill, MA, USA;2. Neurobiology of Social Behavior Laboratory, Department of Psychology & Neuroscience Program, Michigan State University, East Lansing, MI, USA;1. Division of Obstetrics and Gynecology, the University of Western Australia, Perth, Western Australia, Australia;2. Centre for Perinatal and Neonatal Medicine, Tohoku University Hospital, Sendai, Japan;3. Miller School of Medicine, University of Miami, Miami, FL;4. Metabolomics Australia, Center for Microscopy, Characterization and Analysis, the University of Western Australia, Perth, Western Australia, Australia;5. Perinatal Research, Department of Pediatrics, Cincinnati Children’s Hospital Medical Centre, University of Cincinnati, Cincinnati, OH;6. School of Veterinary and Life Sciences, Murdoch University, Perth, Western Australia, Australia |
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| Abstract: | Vasoactive intestinal peptide (VIP) is present in post-ganglionic vagal nerve fibers in the coronary arteries and right ventricle but no significant amounts are found in the left ventricle. We determined the effects of VIP, released endogenously from cardiac vagal nerves, on the circumflex mean coronary artery pressure and on right and left ventricular (RV and LV) contractility (dP/dtmax) and relaxation (dP/dtmin). In 20 anesthetized, open chest mongrel dogs, the cervical vagus nerves and cardiac sympathetic ansa subclaviae were isolated and transected. Electrodes were applied to the cardiac segments of the right and left vagus nerves for subsequent stimulation. The muscarinic and β-adrenergic receptors were blocked with atropine and propranolol, respectively. The heart rate was controlled by either producing atrioventricular node block in 10 dogs and pacing the ventricles (series 1) or by right atrial pacing in 10 separate dogs (series 2). Coronary artery blood flow was controlled by perfusing the circumflex coronary artery in each dog with femoral arterial blood at a controlled flow rate. Coronary artery pressure, ventricular and aortic pressures and dP/dt were continuously measured. Experiments were performed prior to and after the administration of [4Cl-D-Phe6,Leu17]VIP, a sensitive and selective VIP antagonist. Vagal nerve stimulation at 20 Hz (0.5 ms, 20 V) for 5 min significantly decreased the circumflex mean coronary artery pressure by 17% from the control value of 95±2 mmHg in series 1 and by 13% from the control value of 109±2 mmHg in series 2 (both p<0.005). Aortic, LV and RV systolic and end-diastolic pressures, LV dP/dtmax and dP/dtmin, and the EKG did not change. In contrast, RV dP/dtmax and dP/dtmin increased by 22% (p<0.04) and 23% (p<0.02), respectively, in series 1 and by 26% (p<0.02) and 33% (p<0.01), respectively, in series 2. The VIP antagonist, [4Cl-D-Phe6,Leu17]VIP, directly injected into the left circumflex coronary artery, had no effect on coronary, aortic or ventricular pressures, ventricular dP/dt or the EKG. However, 20 Hz vagal stimulation in the presence of the VIP antagonist did not decrease circumflex mean coronary artery pressure. In addition, vagal stimulation, in the presence of the VIP antagonist, had no effect on LV pressures or dP/dt but increased RV dP/dtmax and dP/dtmin. RV dP/dtmax increased by 16% (p<0.01) and RV dP/dtmin increased by 22% (p<0.04), respectively, in series 1 and by 27 and 24%, respectively, in series 2 (both p<0.01). Vagal nerve stimulation during muscarinic and β-adrenergic blockade releases VIP or a `VIP-like' substance that significantly decreases circumflex coronary artery vascular resistance and increases RV dP/dtmax and dP/dtmin. |
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