Role of aspirin activated nitric oxide synthase in controlling DOCA-salt-induced hypertension in rats through the stimulation of renal r-cortexin in kidney cortex cells

Objectives: Because the damage of kidney tissue is associated with hypertension and impaired nitric oxide (NO) synthesis, and as aspirin is reported to stimulate the synthesis of renal r-cortexin, an anti-hypertensive protein, we investigated the role of aspirin as bolus dose on elevated blood pressure induced by deoxycorticosterone acetate (DOCA)-salt in animal model. Methods: The chronic antihypertensive effect of aspirin on DOCA treated with ASA group of rats (n = 6) was evaluated after ingestion of 0.35 mu M aspirin as a bolus dose in every 24 h using tail cuff methods. The plasma aspirin, NO, and r-cortexin levels were determined by spectrophotometric, methemoglobin, and ELISA methods, respectively. Synthesis of r-cortexin mRNA was determined. Aspirin activated nitric oxide synthase (AANOS) was purified by chromatographic methods. Results: Our results showed after 3 h of administration of aspirin (0.35 mu M) to the DOCA treated with ASA group of rats decreased the systolic blood pressure from 139.39 +/- 7.36 mm of Hg to 116.57 +/- 6.89 mm of Hg and diastolic blood pressure from 110.4 +/- 7 mm of Hg to 86.4 +/- 2.76 mm of Hg. The reduction of BPs was found to be related to the increased plasma aspirin from 0.00 mu M to 0.042 mu M, plasma NO from 0.4 +/- 0.19 nM to 1.9 +/- 0.5 nM, and cortexin levels from 64.36 +/- 12.6 nM to 216.7 +/- 21.3 nM. The molecular weight of purified AANOS is 18 kDa. Conclusion: It can be concluded that aspirin possesses antihypertensive effect on blood pressure in chronic administration. Aspirin can stimulate NO synthesis through the activation of AANOS, which stimulated the production of r-cortexin in kidney cortex cells and thereby reducing elevated BP in hypertensive rats.