Fatty acid (FA)–dependent mitochondrial activities of atrial myocardium in hypertension (HTN) and its regulation by nitric oxide (NO) remain unidentified. Here, we have studied palmitic acid (PA) regulation of cardiac mitochondrial oxygen consumption rate (OCR) in left atrial (LA) myocardium of sham and angiotensin II–induced HTN rats and their regulations by endothelial NO synthase (eNOS) and neuronal NO synthase (nNOS). The effects were compared with those of left ventricular (LV) myocytes. Our results showed that OCR was greater in HTN-LA compared with that in sham-LA. PA increased OCR in sham-LA, sham-LV, and HTN-LV but reduced it in HTN-LA. Inhibition of nNOS (S-methyl-l-thiocitrulline, SMTC) or eNOS/nNOS (Nω-nitro-l-arginine methyl ester hydrochloride, l-NAME) reduced PA increment of OCR in sham-LA but exerted no effect on OCR in HTN-LA. SMTC reduced OCR in HTN-LV and l-NAME reduced OCR in sham-LV. nNOS was the predominant source of NO in LA and LV. nNOS-derived NO was increased in HTN-LA and HTN-LV. PA reduced eNOS^Ser1177, nNOS^Ser1417, and NO level in HTN-LA but exerted no effect in sham-LA. In contrast, PA increased NO in HTN-LV and enhanced nNOS^Ser1417 but reduced NO level in sham-LV without affecting eNOS^Ser1177, eNOS^Thr495, or nNOS^Ser1417. 2-Bromopalmitate (2BP), which blocks the S-palmitoylation of target proteins, prevented PA-dependent decrease of nNOS^Ser1417 and OCR in HTN-LA. In HTN-LV, 2BP prevented PA-induced OCR without affecting nNOS^Ser1417. Our results reveal that FA-induced mitochondrial activity in atrial myocardium is impaired in HTN which is mediated by reduced nNOS activity and NO bioavailability. Metabolic dysregulation may underlie diastolic dysfunction of atrial myocardium in HTN.

高血压（HTN）心房心肌的脂肪酸（FA）依赖性线粒体活性及其通过一氧化氮（NO）的调节仍未确定。在这里，我们研究了棕榈酸 (PA) 对假手术和血管紧张素 II 诱导的 HTN 大鼠左心房 (LA) 心肌中心脏线粒体耗氧率 (OCR) 的调节及其通过内皮 NO 合酶 (eNOS) 和神经元 NO 合酶的调节(nNOS)。将这些效果与左心室 (LV) 肌细胞的效果进行比较。我们的结果表明，与假 LA 相比，HTN-LA 的 OCR 更高。PA 在假 LA、假 LV 和 HTN-LV 中增加了 OCR，但在 HTN-LA 中降低了 OCR。抑制 nNOS（S-甲基-l-硫代瓜氨酸，SMTC）或 eNOS/nNOS（Nω-硝基-l-精氨酸甲酯盐酸盐，l -NAME) 降低了 sham-LA 中 OCR 的 PA 增量，但对 HTN-LA 中的 OCR 没有影响。SMTC 降低了 HTN-LV 中的 OCR，而l - NAME 降低了假 LV 中的 OCR。nNOS 是 LA 和 LV 中 NO 的主要来源。nNOS 衍生的 NO 在 HTN-LA 和 HTN-LV 中增加。PA 降低了 HTN-LA 中的eNOS ^Ser1177、nNOS ^Ser1417和 NO 水平，但对假 LA 没有影响。与此相反，在PA HTN-LV增加NO和增强的nNOS ^Ser1417但减少假-LV NO水平，而不影响的eNOS ^Ser1177，eNOS的^Thr495，或nNOS的^Ser1417。2-溴棕榈酸酯 (2BP)，可阻断靶蛋白的S-棕榈酰化，阻止 PA 依赖性 nNOS 减少HTN-LA 中的^Ser1417和 OCR。在 HTN-LV 中，2BP 在不影响 nNOS ^{Ser1417 的}情况下阻止 PA 诱导的 OCR 。我们的结果表明，在 HTN 中，FA 诱导的心房心肌线粒体活性受损，这是由 nNOS 活性和 NO 生物利用度降低介导的。代谢失调可能是 HTN 心房心肌舒张功能障碍的基础。