Nitric oxide (NO) released from a new NO donor has lower activity in vascular smooth muscle cells from renal hypertensive rat

Increased production of superoxide anion (O 2 − ) reduces the biovailability of NO released by the new NO donor cis ‐[Ru(bpy) 2 (py)NO](PF 6 ) 2 (RUNOCL) in rat aortic smooth muscle cells (SMC). NO is a messenger molecule that plays an important role in the control of vascular tone due to the activation of soluble guanylyl cyclase (sGC)‐ cGMP‐ protein kinase G pathway that causes the decrease of cytosolic Ca 2+ concentration ([Ca 2+ ] c ). This study aimed to investigate the effect of the NO released from RUNOCL on the [Ca 2+ ] c in SMC from normotensive (2K) and renal hypertensive rats (2K‐1C). [Ca 2+ ] c , [NO] c and [O 2 − ] c were measured with fluorescent probes FLUO‐3AM (510 nm), DAF‐2DA (545 nm) and DHE (595 nm), respectively, excited by 488 nm using a laser scanning confocal microscopy. [NO] c released from RUNOCL (10 μmol/L) was greater in 2K cells (15.9±0.6%) than in 2K‐1C cells (10.9±1.1%, n=3, P<0.001). On the other hand, in 2K‐1C cells the basal [O 2 − ] was 2.6 times greater than in 2K cells (P<0.05). RUNOCL decreased [Ca 2+ ] c from 100% to 60.0±10%, n=3) in 2K cells and from 100% to 77.2 ± 2%, n=3 (P<0.001) in 2K‐1C cells. These results indicate that the NO donor RUNOCL has greater effect in reducing [Ca 2+ ] c in 2K than in 2K‐1C cells. This impaired effect of the NO donor is related to the lower [NO] c available in 2K‐1C cells. It could be due to an increased production of O 2 − that reacts with NO reducing its bioavailability. Supported by FAPESP and CNPq.