[Effect and mechanism of three kinds of drinking water on blood pressure of hypertensive mice].

OBJECTIVE: To explore the effect of three kinds of drinking water and its possible mechanism on blood pressure of hypertensive mice. METHODS: The water quality parameters were measured for three kinds of drinking water, and the parameters includedtotal dissolved solids( TDS), oxygen consumed( OC), p H, oxidation reduction potential( ORP), electric conductivity( EC), dissolved hydrogen, calcium and magnesium. Establishment of mouse model of high blood pressure by using N'-nitro-L-arginine methyl ester hydrochloride( L-NAME) for 30 days. Then the mice were randomly divided into 4 groups: normal control group, model control group, group of tap water and group of filtered water. Blood pressure in mice was detected every month. After 3 months, nitric oxide( NO), nitric oxide synthase( NOS), total superoxide dismutase( T-SOD), malondialdehyde( MDA), glutathione peroxidase( GSH-Px), endothelin( ET), angiotensin( Ang), aldosterone( ALD), catecholamine( CA), high-sensitivity C-reactive protein( hs-CRP), interleukin 6( IL-6) and cyclic guanosine monophosphate( c-GMP) in serum of the mice were determined. Simultaneously morphological changes of heart, kidney and thoracic aorta paraffin section were observed. RESULTS: The p H, TDS, OC, EC, calcium and magnesium in filtered water were higher than that of pure and tap water. The negative ORP and great quantities of dissolved hydrogen were found in filtered water; The systolic blood pressure and mean blood pressure(( 106. 24 ± 5. 31) and( 90. 73 ± 4. 99)mm Hg) of filtered water were lower than those of the pure water( 119. 58 ± 6. 08 and 96. 44± 6. 48 mm Hg)( P < 0. 05). The NO(( 87. 05 ± 39. 82) µmol/L) in the mice with filtered water were higher than those of with pure and tap water(( 45. 01 ± 9. 62) and( 46. 56 ±30. 54) µmol/L)( P < 0. 05). Compared with those of the mice with pure water, significant decrease in IL-6(( 201. 42 ± 36. 41) and( 173. 99 ± 114. 96) vs. ( 363. 14 ± 149. 00)pg/m L) and Ang(( 1319. 20 ± 111. 90) and( 1349. 38 ± 180. 15) vs. ( 1736. 17 ±242. 86) ng/L) were observed in mice treated with tap and filtered water( P < 0. 05). The T-SOD and GSH-Px(( 268. 37 ± 12. 25) and( 712. 45 ± 30. 59) U/m L) in the mice with filtered water were significant higher than those of pure water(( 250. 46 ± 15. 60) and( 678. 36 ± 35. 80) U/m L)( P < 0. 05). CONCLUSION: Compared with pure and tap water, filtered water can reduce the blood pressure of the hypertensive mice by antioxidation and anti-inflammatory.

Pharmacological postconditioning against myocardial infarction with a slow-releasing hydrogen sulfide donor, GYY4137.

Exogenous hydrogen sulfide (H2S) protects against myocardial ischemia/reperfusion injury but the mechanism of action is unclear. The present study investigated the effect of GYY4137, a slow-releasing H2S donor, on myocardial infarction given specifically at reperfusion and the signalling pathway involved. Thiobutabarbital-anesthetised rats were subjected to 30min of left coronary artery occlusion and 2h reperfusion. Infarct size was assessed by tetrazolium staining. In the first study, animals randomly received either no treatment or GYY4137 (26.6, 133 or 266µmolkg(-1)) by intravenous injection 10min before reperfusion. In a second series, involvement of PI3K and NO signalling were interrogated by concomitant administration of LY294002 or L-NAME respectively and the effects on the phosphorylation of Akt, eNOS, GSK-3ß and ERK1/2 during early reperfusion were assessed by immunoblotting. GYY4137 266µmolkg(-1) significantly limited infarct size by 47% compared to control hearts (P<0.01). In GYY4137-treated hearts, phosphorylation of Akt, eNOS and GSK-3ß was increased 2.8, 2.2 and 2.2 fold respectively at early reperfusion. Co-administration of L-NAME and GYY4137 attenuated the cardioprotection afforded by GYY4137, associated with attenuated phosphorylation of eNOS. LY294002 totally abrogated the infarct-limiting effect of GYY4137 and inhibited Akt, eNOS and GSK-3ß phosphorylation. These data are the first to demonstrate that GYY4137 protects the heart against lethal reperfusion injury through activation of PI3K/Akt signalling, with partial dependency on NO signalling and inhibition of GSK-3ß during early reperfusion. H2S-based therapeutic approaches may have value as adjuncts to reperfusion in the treatment of acute myocardial infarction.

Hypertonicity increases NO production to modulate the firing rate of magnocellular neurons of the supraoptic nucleus of rats.

Increases in plasma osmolality enhance nitric oxide (NO) levels in magnocellular neurosecretory cells (MNCs) of the supraoptic nucleus (SON) and modulate the secretion of both vasopressin (VP) and oxytocin (OT). In this paper, we describe the effects of hypertonicity on the electrical properties of MNCs by focusing on the nitrergic modulation of their activity in this condition. Membrane potentials were measured using the patch clamp technique, in the presence of both glutamatergic and GABAergic neurotransmission blockers, in coronal brain slices of male Wistar rats. The recordings were first made under a control condition (295 mosm/kg H2O), then in the presence of a hypertonic stimulus (330 mosm/kg H2O) and, finally, with a hypertonic stimulus plus 500 µM L-Arginine or 100 µM N-nitro-L-Arginine methyl ester hydrochloride (L-NAME). Hypertonicity per se increased the firing frequency of the neurons. L-Arginine prevented the increase in fire frequency induced by hypertonic stimulus, and L-NAME (inhibitor of nitric oxide synthase) induced an additional increase in frequency when applied together with the hypertonic solution. Moreover, L-Arginine hyperpolarizes the resting potential and decreases the peak value of the after-hyperpolarization; both effects were blocked by L-NAME and hypertonicity and/or L-NAME reduced the time constant of the rising phase of the after-depolarization. These results demonstrate that an intrinsic nitrergic system is part of the mechanisms controlling the excitability of MNCs of the SON when the internal fluid homeostasis is disturbed.