Spranger Marty D, Kaur Jasdeep, Sala-Mercado Javier A, Krishnan Abhinav C, Abu-Hamdah Rania, Alvarez Alberto, Machado Tiago M, Augustyniak Robert A, O'Leary Donal S
Department of Physiology and Cardiovascular Research Institute, Wayne State University School of Medicine, Detroit, Michigan.
Department of Physiology and Cardiovascular Research Institute, Wayne State University School of Medicine, Detroit, Michigan
Am J Physiol Heart Circ Physiol. 2017 Jan 1;312(1):H68-H79. doi: 10.1152/ajpheart.00417.2016. Epub 2016 Oct 21.
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 α-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/dt, and cardiac output were markedly reduced to only 32 ± 13, 26 ± 11, and 28 ± 12% of the changes observed in control. In HTN, α-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.
NEW & NOTEWORTHY: We found that metaboreflex-induced increases in coronary blood flow and ventricular contractility are attenuated in hypertension. α-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.
运动期间心肌氧耗增加主要通过冠状动脉血流量（CBF）增加来实现，因为即使在静息时心脏的氧摄取率也很高。然而，交感神经对冠状动脉的收缩作用会限制CBF的增加。运动期间交感神经活动（SNA）增加可能是通过骨骼肌传入神经激活、中枢指令以及动脉压力反射重调定的作用和相互作用而发生的。由于高血压（HTN）患者即使在静息时SNA也会升高，我们测试了HTN是否会在轻度跑步机运动并激活肌肉代谢反射（MMA；通过将后肢血流量减少约60%引发）期间导致犬类冠状动脉过度收缩，从而限制CBF增加和心室功能。在α-肾上腺素能阻断（哌唑嗪；75μg/kg）后以及在同一动物诱导HTN（改良的Goldblatt 2K1C模型）后重复实验。HTN使静息时平均动脉压从97.1±2.6 mmHg升高至132.1±5.6 mmHg，MMA诱导的CBF、左心室dP/dt和心输出量增加显著降低，仅为对照中观察到变化的32±13%、26±11%和28±12%。在HTN中，α-肾上腺素能阻断恢复了冠状动脉舒张并使心室功能增加至血压正常时观察到的水平。我们得出结论，MMA诱导的SNA过度增加在功能上使冠状动脉血管收缩，损害CBF增加，这限制了HTN中的氧输送和心室功能。
我们发现代谢反射诱导的冠状动脉血流量和心室收缩力增加在高血压中减弱。α-肾上腺素能阻断使这些参数恢复到正常水平。这些发现表明，介导高血压中代谢反射诱导的心室功能增加受损的主要机制是冠状动脉过度收缩。
