title: Exaggerated coronary vasoconstriction limits muscle metaboreflex-induced increases in ventricular performance in hypertension.
abstract: Increases in myocardial oxygen consumption during exercise mainly occur via increases in coronary blood flow (CBF) as cardiac oxygen extraction is high even at rest. However, sympathetic coronary constrictor tone can limit increases in CBF. Increased sympathetic nerve activity (SNA) during exercise likely occurs via the action of and interaction among activation of skeletal muscle afferents, central command, and resetting of the arterial baroreflex. As SNA is heightened even at rest in subjects with hypertension (HTN), we tested whether HTN causes exaggerated coronary vasoconstriction in canines during mild treadmill exercise with muscle metaboreflex activation (MMA; elicited by reducing hindlimb blood flow by ~60%) thereby limiting increases in CBF and ventricular performance. Experiments were repeated after α1-adrenergic blockade (prazosin; 75 µg/kg) and in the same animals following induction of HTN (modified Goldblatt 2K1C model). HTN increased mean arterial pressure from 97.1 ± 2.6 to 132.1 ± 5.6 mmHg at rest and MMA-induced increases in CBF, left ventricular dP/dtmax, and cardiac output were markedly reduced to only 32 ± 13, 26 ± 11, and 28 ± 12% of the changes observed in control. In HTN, α1-adrenergic blockade restored the coronary vasodilation and increased in ventricular function to the levels observed when normotensive. We conclude that exaggerated MMA-induced increases in SNA functionally vasoconstrict the coronary vasculature impairing increases in CBF, which limits oxygen delivery and ventricular performance in HTN.
  We found that metaboreflex-induced increases in coronary blood flow and ventricular contractility are attenuated in hypertension. α1-Adrenergic blockade restored these parameters toward normal levels. These findings indicate that the primary mechanism mediating impaired metaboreflex-induced increases in ventricular function in hypertension is accentuated coronary vasoconstriction.
authors: Department of Physiology and Cardiovascular Research Institute, Wayne State University School of Medicine, Detroit, Michigan.
authors: Marty D
authors: MD
authors: Spranger
authors: Department of Physiology and Cardiovascular Research Institute, Wayne State University School of Medicine, Detroit, Michigan.
authors: Jasdeep
authors: J
authors: Kaur
authors: Department of Physiology and Cardiovascular Research Institute, Wayne State University School of Medicine, Detroit, Michigan.
authors: Javier A
authors: JA
authors: Sala-Mercado
authors: Department of Physiology and Cardiovascular Research Institute, Wayne State University School of Medicine, Detroit, Michigan.
authors: Abhinav C
authors: AC
authors: Krishnan
authors: Department of Physiology and Cardiovascular Research Institute, Wayne State University School of Medicine, Detroit, Michigan.
authors: Rania
authors: R
authors: Abu-Hamdah
authors: Department of Physiology and Cardiovascular Research Institute, Wayne State University School of Medicine, Detroit, Michigan.
authors: Alberto
authors: A
authors: Alvarez
authors: Department of Physiology and Cardiovascular Research Institute, Wayne State University School of Medicine, Detroit, Michigan.
authors: Tiago M
authors: TM
authors: Machado
authors: Department of Physiology and Cardiovascular Research Institute, Wayne State University School of Medicine, Detroit, Michigan.
authors: Robert A
authors: RA
authors: Augustyniak
authors: Department of Physiology and Cardiovascular Research Institute, Wayne State University School of Medicine, Detroit, Michigan doleary@med.wayne.edu.
authors: Donal S
authors: DS
authors: O'Leary
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D062186:Arterial Pressure; D002302:Cardiac Output / Q000187:drug effects / Q000502:physiology*; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology*; D003331:Coronary Vessels / Q000187:drug effects / Q000503:physiopathology*; D004285:Dogs; D005260:Female; D006614:Hindlimb / Q000098:blood supply; D006973:Hypertension / Q000503:physiopathology; D006978:Hypertension, Renovascular / Q000503:physiopathology*; D018482:Muscle, Skeletal / Q000098:blood supply; D010805:Physical Conditioning, Animal; D011224:Prazosin / Q000494:pharmacology; D012018:Reflex; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D016276:Ventricular Function / Q000187:drug effects / Q000502:physiology*
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D011224:Prazosin
keywords: contractility; coronary blood flow; exercise pressor reflex; hypertension