The brainstem, the core of the central nervous system, plays a vital role in controlling arterial blood pressure and its elevation of hypertension subtypes, especially essential hypertension. Integrative metabolic and proteomic profiling was performed on the brainstem samples of 11-week-old spontaneously hypertensive rats (SHRs) and age-matched normotensive Wistar rats, using hydrophilic interaction liquid chromatography-quadrupole/time-of-flight mass spectrometry (HILIC-Q/TOFMS) and nano-liquid chromatography-high-resolution-mass spectrometry (nano-LC-high-resolution-MS) combined with quantitative tandem mass tags (TMT).