Effect Of Nitroglycerin And Sympathetic Withdrawal On Splanchnic Capacitance And Cardiac Blood Volumes

The splanchnic vasculature is the largest blood volume reservoir in the human body. Reduced capacitance of this vascular bed, in part due to sympathetic venoconstriction, is proposed to play a role in hypertension and heart failure. Thus, interventions that increase splanchnic capacitance or decrease sympathetic activity may be beneficial in these conditions. In a proof-of-concept study in healthy and hypertensive subjects, we evaluated whether venodilation with nitroglycerin (NTG; Study 1) or sympathetic withdrawal with trimethaphan (Study 2) increase splanchnic capacitance and reduce cardiac and stroke volumes. In Study 1 (n=10, 36±4 yrs, BMI 26.1±1.7, 4 men), abdominal and chest scintigrams, to measure regional blood volumes, were obtained before and after 0.6 mg sublingual NTG. Splanchnic capacitance (volume-pressure relationships, VPR) and compliance (VPR slope) were estimated by recording abdominal scintigrams during progressive escalation of intrathoracic pressure using continuous positive airway pressure (CPAP) at 0, 4, 8, 12, and 16 cm H 2 O, each for ≤2 min. We found that NTG increased splanchnic blood volume at rest (4%, IQR 1.81-9.95; P<0.01) resulting in a rightward parallel shift in splanchnic VPR (P slope =0.46 and P intercept =0.01), indicating an increase in splanchnic capacitance. This was associated with a decrease in cardiac blood volume (-9%, IQR 2.2-10.3; P<0.01). In Study 2, we measured blood pressure (BP) and stroke volume, used as a surrogate of venous return, during the same CPAP protocol before and during autonomic blockade with trimethaphan in 12 hypertensive subjects (49±2 yrs, BMI 29.9±1.7, 5 men). Sympathetic withdrawal decreased systolic BP (-27±14 mmHg) and produced a leftward parallel shift in VPR (i.e. reduced stroke volume; P slope =0.12 and P intercept <0.01), indicating a reduction in venous return likely due to an increase in splanchnic capacitance. In conclusion, venodilation with NTG increased splanchnic capacitance and decreased cardiac volume. Sympathetic withdrawal had similar hemodynamic effects. These findings highlight the importance of splanchnic capacitance in cardiovascular regulation.