Palmitic Acid Regulation of Cardiac Inotropy and Calcium Handling in Healthy and Angiotensin II‐Induced Hypertensive Rat

Abstract

Background and aimPalmitic acid (PA) is a predominant metabolic substrate. However, the effect of PA on cardiac contraction and underlying mechanisms in healthy and diseased heart remain unclear. Here, we analyzed PA‐regulation of myocyte contraction in left ventricular (LV) myocytes from sham and angiotensin II (Ang II)‐induced hypertensive rats.ResultsOur results showed that PA (100 μM) increased the amplitude of sarcomere shortening in LV myocytes (field stimulation, 2Hz,IonOptix Corp) from shams but not in hypertension. PA increased intracellular ATP level in shams.In contrast, etomoxir, a selective carnitine palmitoyl transferase I inhibitor, blunted the positive inotropic effect of PA, suggesting that increased beta‐oxidation may be fundamentally importantin PA‐regulation of cardiac inotropy. Mechanistically, PA did not increase the amplitude of Ca2+ transients or the density of peak L‐type Ca2+ current (ICa) or Na+‐Ca2+ exchanger activity, INCX, in either group. Paradoxically, PA did not affect the amplitude of Ca2+ transient or myofilament Ca2+ sensitivity (Myo‐Ca‐Sen) in shams. In hypertension, PA did not affect myocyte contraction or Ca2+ transient amplitude. Reactive oxygen species (ROS) scavenger did not affect PA‐induced increase in LV myocyte contraction in sham or hypertension.PA reduced neuronal nitric oxide synthase (nNOS) production of NO in shams but increased nNOS production of NO in hypertension. Importantly, nNOS inhibition with S‐methyl‐l‐thiocitrulline (SMTC) increased the amplitude of Ca2+ transients and restored PA‐induced cardiac inotropy in hypertension.ConclusionPA increases myocardial ATP production and potentiates LV myocyte contraction in healthy heart. nNOS restricts PA‐dependent cardiac inotropy by modulating Ca2+ handling in hypertension.