Abstract P49: Periodic Acceleration (pGz) Increases Endothelial and Neuronal Nitric Oxide Synthase in Healthy Rat Heart
Whole body periodic acceleration (pGz) is the sinusoidal motion of the body in a head-foot direction in the spinal axis. pGz is a novel method to increase pulsatile vascular shear stress. pGz increases regional blood flow to vital organs, provides cardiopulmonary support during CPR with cardioprotective properties, and increases nitrite (a marker for nitric oxide production) in vivo and in vitro.
Hypothesis: pGz through increased pulsatile stress increases NO production by increased phosphorylation of eNOS as well as upregulating expression of nitric oxide synthase isoforms (NOS).
Methods: Male (300±15 g) unsedated restrained rats were randomized to two groups: Control (n=4), and pGz (n=8) who received 1 hour pGz treatment at a frequency of 360 cpm (6 Hz) and Gz force of ±3.5 m/sec2. Heart and lungs were harvested at 4 and 24 hours after these interventions for protein levels of NOS isoforms, Akt and ERK1/2 pathways by immunoblotting analysis.
Results: pGz had no significant effect on heart rate, blood pressure or blood gases. Compared to the controls, pGz significantly increased nitrosylated protein levels (130% of Control, p<0.05) indicating increased NO production. The phosphorylated eNOS (Ser-1177) levels increased to 261% of Control (p<0.05). As early as 4 hrs after pGz, cardiac eNOS protein levels increased to 393% of Control (p<0.05) and lungs to 238% of Control (p<0.01). The increase lasted at least 24 hours after pGz was discontinued. pGz also significantly increased Akt phosphorylation at Thr 308 to 217% of Control (p<0.05) without change in total Akt or phosphorylated ERK1/2. nNOS levels in heart also significantly increased to 167% of Control (p<0.01). iNOS levels, in both heart and lungs, were undetectable in either pGz or Control.
Conclusion: pGz increased NO production by increasing eNOS phosphorylation. pGz upregulated eNOS and nNOS in heart, and, eNOS in lung, which are ERK1/2-independent. We postulate that upregulation of eNOS and nNOS by pGz is at least partly mediated through Akt pathway, but the exact mechanism needs to be further explored. The cardioprotective properties observed with pGz are in part related to its ability to increase NO production and upregulate the attendant NOS isoforms eNOS and nNOS via increased pulsatile shear stress.