Gravity-dependent blood pressure rise in essential hypertension: mechanism of orthostatic hypertension

Background: Orthostatic hypertension (oHTN)—a paradoxical increase in blood pressure upon standing—remains understudied despite its association with increased cardiovascular risk in individuals with essential hypertension. The role of low-pressure cardiopulmonary reflexes in mediating this condition is not well understood. Objective: This study aimed to determine whether greater reductions in central blood volume (CBV) from venous pooling during orthostatic stress, increased sensitivity of the low pressure cardiopulmonary reflex to this blood pooling, or both, contribute to the pathophysiology of oHTN. Materials and Methods: Twenty-three patients with untreated essential hypertension underwent graded head-up tilt testing (15°, 25°, 35°) to evaluate CBV changes using indocyanine green dye dilution. Simultaneous measurements of arterial pressure, total peripheral resistance index (TPRI), and plasma renin activity were recorded. Patients in the top quintile of diastolic blood pressure (DBP) response during tilt were categorized as having oHTN. Results: Patients with oHTN exhibited significantly greater CBV reduction (−28.6% vs. −19.5% at 35°; p < 0.05), steeper increases in TPRI (46.2% vs. 11.9%; p < 0.01), and greater increase in plasma renin activity (2.23 vs. 0.77 ng/ml/h; p < 0.05) compared to non-oHTN patients. A direct correlation between fall in CBV and increase in TPR was observed, suggesting a volume-sensitive reflex mechanism, but gain of the low pressure cardiopulmonary reflex (ΔTPR/ΔCBV) was normal, not contributing to the exaggerated hemodynamic changes. Conclusions: oHTN is characterized by excessive vasoconstriction and neurohumoral activation in response to exaggerated central hypovolemia during orthostatic stress. These findings support a pivotal role for the volume-sensitive reflex—rather than the arterial baroreflex—in the development of oHTN and identify potential therapeutic targets.