Chronic effects of direct vasodilation (pinacidil), alpha-adrenergic blockade (prazosin) and angiotensin-converting enzyme inhibition (captopril) in systemic hypertension |
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| Authors: | J L Izzo M R Licht R J Smith P S Larrabee K J Radke M C Kallay |
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| Affiliation: | 1. Department of Medicine, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA 70112, USA;2. Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, 1440 Canal Street, New Orleans, LA 70112, USA;3. Center for Health Research, Ochsner Clinic Foundation, 1514 Jefferson Highway, New Orleans, LA 70121, USA;1. Department of Medicine and Surgery, University of Milano-Bicocca, Milano, Italy;2. Istituto Auxologico Italiano, Milano, Italy;3. Department of Cardiology, Charité-University-Medicine Campus Virchow Klinikum, Berlin, Germany;4. IRCCS Multimedica, Sesto San Giovanni, Milano, Italy;5. University Children''s Hospital, Zurich, Switzerland;6. University Hospital Motol, Prague, Czech Republic;7. Shanghai Jiao Tong University, Shanghai, China;8. Department of Paediatrics, School of Medicine, University of Granada, Granada, Spain;9. Polytechnic University of Marche, Ancona, Italy;10. Université de Nantes, Nantes, France;11. Department of Pediatrics, University of Pécs, Pécs, Hungary;12. Department of Clinical Sciences, Pediatrics, Umeå University, Sweden;13. Newcastle University, Newcastle upon Tyne, UK;14. UCL Great Ormond Street Institute of Child Health, London, UK;15. University Medical Centre Ljubljana, Ljubljana, Slovenia;p. University Children''s Hospital, Tuebingen, Germany;q. University Sordonne-Paris-Cité, France;r. Paris-Descartes Medical School, Paris, France;s. Schneider Children''s Medical Center of Israel, Petach Tikva, Israel;t. Carmel Medical Center, Haifa, Israel;u. Great Ormond Street Hospital for Children, NHS Foundation Trust, UCL Institute of Child Health, London, UK;v. Children''s Hospital Zagreb, University of Zagreb School of Medicine, University of J. J. Strossmayer School of Medicine Osijek, Croatia;w. CHU La Réunion, Saint Pierre, France;x. Ev. Waldkrankenhaus Spandau, Berlin, Germany;y. Department of Pediatrics and Pediatric Surgery, Intensive Care, Erasmus MC-Sophia Children''s Hospital, Rotterdam, The Netherlands;z. Children''s Hospital, University of Zagreb School of Medicine, Zagreb, Croatia;11. k LMU – Ludwig-Maximilians-Universität Munich, Dr. von Hauner Children''s Hospital, Munich, Germany;12. Department of Pediatrics, Nutrition and Metabolic Diseases, The Children''s Memorial Health Institute, Warsaw, Poland;13. Paris-Descartes University, Paris, France;14. KU Leuven, Leuven, Belgium;15. Ulm University, Ulm, Germany;16. Helios Hospital, Pforzheim, Germany;17. Department of Pediatrics, Division of Neonatology, The Wilf Children''s Hospital, The Shaare Zedek Medical Center, Jerusalem, Israel;18. Tel Aviv University, Tel Aviv, Israel;19. Department of Nutrition, Exercise and Sports, University of Copenhagen, Paediatric Nutrition Unit, Rigshospitalet, Copenhagen, Denmark;110. Oslo University Hospital, Oslo, Norway;111. Laboratoire CarMEN, Claude Bernard University Lyon 1, Hopital croix rousse, Lyon, France;112. LMU – Ludwig-Maximilians-Universität Munich, Dr. von Hauner Children''s Hospital, Munich, Germany;113. The General Infirmary at Leeds, Leeds, UK;114. Bnai Zion Medical Center, Rappaport Faculty of Medicine, Technion, Haifa, Israel;115. Department of Neonatology, La Paz University Hospital, Red de Salud Materno Infantil y Desarrollo – SAMID, Universidad Autónoma de Madrid, Madrid, Spain;1p. CHU de Liège, CHR de la Citadelle, Université de Liège, Belgium;1q. Great Ormond Street NHS Trust, London, UK;1r. General University Hospital, First Faculty of Medicine, Charles University in Prague, Czech Republic;1s. Emma Children''s Hospital, Amsterdam UMC, Amsterdam, The Netherlands;1t. OLVG, Amsterdam, The Netherlands;1u. Xin Hua Hospital, Shanghai, China;1v. Department of Gastroenterology and Nutrition, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China;1. Erasmus MC-Sophia Children''s Hospital, Rotterdam, The Netherlands;2. Newcastle Neonatal Service, Newcastle Hospitals NHS Trust & Newcastle University, Newcastle upon Tyne NE1 4LP, UK;3. Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China;4. Service Universitaire de Néonatologie, Centre Hospitalier Régional (CHR) de la Citadelle, Centre Hospitalier Universitaire (CHU) de Liège, Université de Liège, Belgium;1. Division of Pulmonary, Critical Care, and Sleep Medicine, Icahn School of Medicine at Mount Sinai, 1 Gustave L Levy Place, PO Box 1232, New York, NY 10029, USA;2. Pulmonary and Intensive Care at Universite de Bourgogne, 1 Rue Marion, F21079, Dijon, France;1. Department of Medicine, University of Virginia, Charlottesville, Virginia;2. Department of Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama;3. Departments of Population Health Sciences, Medicine, Psychiatry and Behavioral Sciences and School of Nursing, Duke University, Durham, North Carolina;4. Department of Epidemiology, Tulane University, New Orleans, Louisiana |
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| Abstract: | Chronic responses of systemic hemodynamics and blood pressure counterregulatory ("pseudo-tolerance") mechanisms were investigated in matched groups of patients with essential hypertension after 1 month of vasodilator therapy with pinacidil (a direct arterial dilator), prazosin (an alpha 1-adrenergic blocking drug) or captopril (an angiotensin-converting enzyme inhibitor). For equivalent decreases in mean arterial pressure compared with placebo baseline (approximately 8 mm Hg supine and 12 mm Hg upright), prazosin and captopril did not increase cardiac index or heart rate. In contrast, marked decreases in systemic vascular resistance with pinacidil (approximately 25%, p less than 0.05) were accompanied by reflex increases in cardiac index (approximately 20%, p less than 0.05). Activity of the sympathetic nervous system, measured by supine and upright plasma norepinephrine (NE), increased approximately 50% with pinacidil and prazosin (p less than 0.001 each), whereas captopril decreased supine plasma NE by 12% (p less than 0.05) and did not change upright plasma NE. All 3 drugs caused an expansion of height-adjusted blood volume (approximately 14%). Pinacidil and prazosin caused reversible weight gains of 0.9 and 0.7 kg, respectively, whereas captopril reversibly decreased body weight by 0.8 kg (p less than 0.05), suggesting differential effects of the 3 drugs on interstitial fluid volume. During chronic therapy, all 3 drugs may require concomitant diuretic therapy, whereas concomitant sympatholytic therapy may be required with the potent vasodilator pinacidil. Captopril may be associated with the lowest cardiac risk because of its lack of stimulatory effects on the sympathetic nervous system and cardiac index. |
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