Oxymatrine improves palmitic acid-induced vascular endothelial cell injury through Akt-eNOS-NO signaling pathway / 中国药理学通报

Aim To investigate the protective effect of oxymatrine (OMT) on vascular endothelial cell injury induced by palmitic acid ( PA) and its mechanism. Methods Cell viability was detected by MTT assay. Cell apoptosis was detected by flow cytometry. The levels of oxygen species ( ROS) in cells, and lactate de-hydrogenase, malondialdehyde (MDA), superoxide dismutase (SOD) , glutathione peroxidase (GSH-PX) and nitric oxide ( NO) in cell culture medium were detected by ELISA. The protein expressions of bcl-2, bax, caspase-3, Akt and eNOS in HUVECs were detected by Western blot. Results OMT significantly inhibited PA-induced decrease in cell viability and increase in level of LDH in HUVECs. OMT also significantly inhibited PA-induced increase in cell apoptosis, and up-regulated the protein expression ratio of bcl-2/ bax and down-regulated the protein expression of caspase-3. In addition, OMT reduced the levels of ROS and MDA, and increased the levels of SOD, GSH-Px and NO in cell-culture medium treated with PA. Furthermore, OMT increased the protein phospho-rylation of Akt and eNOS in injured cells. Conclusion OMT ameliorates PA-induced vascular endothelial cell injury through Akt-eNOS-NO signaling pathway.

Ca2+-induced Ca2+ Release from Sarcoplasmic Reticulum Negatively Regulates Myocytic ANP Release in Beating Rabbit Atria

It is not clear whether Ca2+-induced Ca2+ release from the sarcoplasmic reticulum (SR) is involved in the regulation of atrial natriuretic peptide (ANP) release. Previously, we have shown that nifedipine increased ANP release, indicating that Ca2+ entry via voltage-gated L-type Ca2+ channel activation decreases ANP release. The purpose of the present study was two-fold: to define the role of SR Ca2+ release in the regulation of ANP release and whether Ca2+ entry via L-type Ca2+ channel is prerequisite for the SR-related effect on ANP release. Experiments were performed in perfused beating rabbit atria. Ryanodine, an inhibitor of SR Ca2+ release, increased atrial myocytic ANP release (8.69+/-3.05, 19.55+/-1.09, 27.31+/-3.51, and 18.91+/-4.76% for 1, 2, 3, and 6microM ryanodine, respectively; all P< 1) with concomitant decrease in atrial stroke volume and pulse pressure in a dose-dependent manner. In the presence of thapsigargin, an inhibitor of SR Ca2+ pump, ryanodine-induced increase in ANP release was not observed. Thapsigargin attenuated ryanodine-induced decrease in atrial dynamic changes. Blockade of L-type Ca2+ channel with nifedipine abolished ryanodine-induced increase in ANP release (0.69+/-5.58% vs. 27.31+/-3.51%; P< 0.001). In the presence of thapsigargin and ryanodine, nifedipine increased ANP release and decreased atrial dynamics. These data suggest that Ca2+-induced Ca2+ release from the SR is inversely involved in the regulation of atrial myocytic ANP release.

Effects of K+ Channel Opener WAY120491 on Renal Function in Rabbits / 대한신장학회잡지

BACKGROUND: K+ channel opener has been considered as a vasorelaxing agent working through hyperpolarization of vascular smooth muscle cells. Renal tubules-proximal, thick ascending limb of Henle and cortical collecting duct-are the site of the diversity of the K+ channel. ATP-sensitive K+ channel has been observed in the apical membranes of the thick ascending limb of Henle and collecting duct, and basolateral membrane of the proximal tubule. It was also shown that K+ channel opener increased renal hemodynamics and elicited diuretic and natriuretic effects. METHODS: To clarify the renal effects of WAY120491, a K+ channel opener, experiments were performed in unanesthetized normotensive and renal hypertensive rabbits allowing unilateral renal arterial infusion of agent. RESULTS: Intrarenal arterial infusion (0.13, 0.32 and 0.64 microgram/kg/min) of WAY120491 increaased CPAH, CCr, urine volume, UNaV, UKV and CH2O. Renal hemodynamic effects and increments of urine volume and free water clearance were completely blocked by glibenclamide (8.2 g/kg/min), while increments of UNaV and FENa were not significantly affected. Renal hemodynamic and tubular effects of WAY120491 were not significantly different in two-kidney one clip Goldblatt hypertensive rabbits from sham-operated rabbits. CONCLUSIONS: These results suggest that WAY120491 elicits renal effects through ATP-sensitive K+ channel in the renal vasculatures and renal tubules and the renal effects of WAT120491 may not be altered in the hypertension.

Effects of Intrarenal Arterial Infusion of Atrial Natriuretic Peptide Analogs on Renal Function in Unanesthetized Rabbits / 대한신장학회잡지

BACKGROUND: Atrial cardiomyocytes synthesize, store and release atrial natriuretic peptide(ANP) which has potent physiological effects, including natriuresis, diuresis, relaxation of vascular smooth muscle and inhibition of aldosterone and renin secretion. A family of atrial peptides are derived from a precursor proANP. However, the structure-activity relationship of several C-terminal ANPs are not yet well documented. METHODS: The effects of structural difference of ANP analogs on the renal function were studied with a sensitive and reproducible bioassay using intrarenal arterial infusion in unanesthetized rabbits. RESULTS: Rat ANP-(1-28)(rANP, 12-Ile), a-human ANP-(1-28)(hANP, 12-Met), atriopeptin III [APIII, rANP-(5-28)], atriopeptin II[APII, rANP-(5- 27)], atriopeptin I[API, rANP-(5-25)], a-human ANP- (7-28)[hANP-(7-28)], and ANP fragments(13-28) [ANP-(13-28)] and (17-28)[ANP-(17-28)] were infused into left renal artery. No significant differences were observed between rANP and hANP. Diuretic and natriuretic activities of APIII were significantly lower than those of rANP and hANP, but were similar to those of hANP-(7-28). Diuretic and natriuretic effects of APII were similar to rANP and hANP in terms of peak responses. Duration of the effects of APII were longer than those of rANP and hANP. No significant changes were observed by infusions of API, and ANP fragments, ANP-(13-28) and ANP-(17-28). rANP, hANP and APIII decreased active but increased inactive renin secretion. CONCLUSION: These data suggest that substitution of isoleucine to methionine at 12 position of ANP does not affect the renal effects of ANP and that disulfide bond and C-terminal segment of ANP are important for the possession of natriuretic and diuretic activities.