Effect of iron oxide nanoparticles on vascular function and nitric oxide production in acute stress-exposed rats.

We investigated whether polyethylene glycol-coated Fe3O4 nanoparticles (IONs), acute stress and their combination modifies vascular functions, nitric oxide synthase (NOS) activity, mean arterial pressure (MAP) as well as hepcidin and ferritin H gene expressions in Wistar-Kyoto rats. Rats were divided into control, ION-treated rats (1 mg Fe/kg i.v.), repeated acute air-jet stress-exposed rats and IONs-and-stress co-exposed rats. Maximal acetylcholine (ACh)-induced and sodium nitroprusside (SNP)-induced relaxations in the femoral arteries did not differ among the groups. IONs alone significantly elevated the N?-nitro-L-arginine methyl ester (L-NAME)-sensitive component of ACh-induced relaxation and reduced the sensitivity of vascular smooth muscle cells to SNP. IONs alone also elevated NOS activity in the brainstem and hypothalamus, reduced NOS activity in the kidneys and had no effect in the liver. Acute stress alone failed to affect vascular function and NOS activities in all the tissues investigated but it elevated ferritin H expression in the liver. In the ION-and-stress group, NOS activity was elevated in the kidneys and liver, but reduced in the brainstem and hypothalamus vs. IONs alone. IONs also accentuated air-jet stress-induced MAP responses vs. stress alone. Interestingly, stress reduced ION-originated iron content in blood and liver while it was elevated in the kidneys. In conclusion, the results showed that 1) acute administration of IONs altered vascular function, increased L-NAME-sensitive component of ACh-induced relaxation and had tissue-dependent effects on NOS activity, 2) ION effects were considerably reduced by co-exposure to repeated acute stress, likely related to decrease of ION-originated iron in blood due to elevated decomposition and/or excretion.

Lack of reactive oxygen species deteriorates blood pressure regulation in acute stress.

This study investigated the contribution of reactive oxygen species (ROS) to blood pressure regulation in conscious adult male Wistar rats exposed to acute stress. Role of ROS was investigated in rats with temporally impaired principal blood pressure regulation systems using ganglionic blocker pentolinium (P, 5 mg/kg), angiotensin converting enzyme inhibitor captopril (C, 10 mg/kg), nitric oxide synthase inhibitor L-NAME (L, 30 mg/kg) and superoxide dismutase mimeticum tempol (T, 25 mg/kg). Mean arterial pressure (MAP) was measured by the carotid artery catheter and inhibitors were administered intravenously. MAP was disturbed by a 3-s air jet, which increased MAP by 35.2+/-3.0 % vs. basal MAP after the first exposure. Air jet increased MAP in captopril- and tempol-treated rats similarly as observed in saline-treated rats. In pentolinium-treated rats stress significantly decreased MAP vs. pre-stress value. In L-NAME-treated rats stress failed to affect MAP significantly. Treatment of rats with P+L+C resulted in stress-induced MAP decrease by 17.3+/-1.3 % vs. pre-stress value and settling time (20.1+/-4.2 s). In P+L+C+T-treated rats stress led to maximal MAP decrease by 26.4+/-2.2 % (p<0.005 vs. P+L+C) and prolongation of settling time to 32.6+/-3.3 s (p<0.05 vs. P+L+C). Area under the MAP curve was significantly smaller in P+L+C-treated rats compared to P+L+C+T-treated ones (167+/-43 vs. 433+/-69 a.u., p<0.008). In conclusion, in rats with temporally impaired blood pressure regulation, the lack of ROS resulted in greater stress-induced MAP alterations and prolongation of time required to reach new post-stress steady state.