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Heat stress (HS) drastically reduces the yield and quality of wheat grains. High temperature during critical stages (pollination and grain-filling) causes improper fertilization and formation of defragmented granules and shriveled seeds. Hormones and signaling molecules modulates the tolerance potential of the plants under stress. Nitric oxide (NO) is an important signaling molecule involved in triggering diverse physiological and bio-chemical processes under adverse conditions. Here, we studied the effect of sodium nitroprusside (SNP) (150 mu M set based on pilot experiment) on heat stress-tolerance and grain quality related traits of two contrasting wheat cultivars Raj3765 as thermotolerant and HD2932 as thermosusceptible under differential HS (T-1 - 30 degrees C, 1 h; T-2 - 38 degrees C, 1 h), as compared to control (22 +/- 2 degrees C) at different stages of growth. The expression of many important stress-associated genes (previously identified through Transcriptome sequencing) was observed upregulated in response to NO and HS; small HSP17 showed maximum fold increase in Raj3765. Similarly, the networks of antioxidant enzymes (SOD, CAT, and GPX) were observed triggered in response to NO, HS and NO + HS treatment in Raj3765 than HD2932. The accumulation of proline and free amino acid in cytoplasm were also reported higher under NO and HS treatment respectively in Raj3765, as compared to HD2932. Grain quality related traits like carbohydrate (starch) and proteins (gliadin) were observed higher in response to NO under HS in Raj3765. Heat stress was observed to increase the activities of alpha/beta amylases in developing grains involved in degrading the starch quality. NO was observed to decrease the amylolytic activity in both the cultivars; very low amylolytic activity was observed in thermotolerant, as compared to thermosusceptible cultivars. Exogenous application of NO (150 mu M) at different stages can be used as inexpensive technology for mitigating the problem of terminal HS in wheat - a farmer friendly approach for maintaining the quality of grains under present threat of global climate change.