Total Body Irradiation Affects the Integrity of Nitric Oxide/cGMP Signaling in Rat Tissues

Vascular injury is one of the most common effects of radiation exposure and its molecular mechanisms remain unknown. NO/cGMP signaling pathway is critical for regulating vascular tone and platelets aggregation. Experimental Design Control and irradiated rats (male, conscious, N=5/group) were used. Irradiated animals received a cumulative dose of 2 Gy (0.1 Gy/min) and sacrificed 3 hrs post exposure in parallel with the control group. Lysates were prepared from vascular bed‐rich tissues (heart, lung, kidney, liver and gut) and analyzed for nitrite/nitrates contents by HPLC. Results were normalized to total protein in lysates and expressed as mean ± SD. cGMP‐dependant protein kinase (PKG) was assessed by Western blotting, analyzed by densitometry and normalized to β‐actin. Results 2 Gy irradiation decreased the total content of nitrite in gut and kidney. Nitrate content significantly decreased in all tissues with highest changes occurring in kidney. There was a decrease in protein expression of sGC subunits in lung: α1 (49.9 ± 16.4%); kidney: α1 (58.1 ± 4.2%); β1 (57.7 ± 7.6%). No changes in PKG protein levels were detected. Conclusion Our data demonstrate 2 Gy irradiation affects levels of nitrogenic compounds and sGC protein as early as 3 hrs. post exposure. This data suggest irradiation impairs NO/cGMP signaling which can result in blunted NO vasorelaxation response.