ABSTRACT
OBJECTIVE： To study the vasodilatory effect of oxysophocarpine （OSC） on isolated thoracic aortic rings of rats and its possible mechanism. METHODS： Thoracic aortic rings of rats were collected （called “vascular ring” for short）. Using K-H nutrient solution as blank control and the diastolic rate as index， the effects of different concentrations （0.2-1.0 mg/mL） of OSC on normal vascular rings in basal state， normal or endothelium-free vascular rings pre-contracted by norepinephrine （PE， 1×10－6 mol/L） were investigated. After pre-culturing normal thoracic aortic rings by nitric oxide synthase inhibitor L-nitro-arginine methyl ester（L-NAME）and cyclooxygenase inhibitor indomethacin（INDO），as well as pre-culturing endothelium-free vascular rings by potassium ion channel blocker BaCl2，tetraethylammonium（TEA）and 4-aminopyridine（4-AP）， the diastolic effects of OSC of different concentrations （0.2-1.0 mg/mL） on the above vascular rings were investigated by using the same method. RESULTS： Compared with blank control， there was no significant effects of different concentrations of OSC on the diastolic rate of normal vascular rings in basal state （P＞0.05）， but 0.4-1.0 mg/mL OSC could significantly improve the diastolic rate of normal or endothelium-free vascular rings pre-contracted by PE （P＜0.01）， in concentration-dependent manner. After preculturing with L-NAME， INDO， 4-AP and BaCl2， different concentrations of OSC had no significant effect on the diastolic rate of normal or endothelium-free vascular rings pre-contracted by PE （P＞0.05）. After pre-culturing with TEA and Gli， 0.4-1.0 mg/mL OSC could significantly reduce the diastolic rate of endothelium-free vas- cular rings pre-contracted by PE （P＜0.01）. CONCLUSIONS： OSC did not significantly dilate the thoracic aortic rings of rats in the basal state within the dose range （0.2-1.0 mg/mL）， but OSC of 0.4-1.0 mg/mL have significant diastolic effects on the normal or endothelium-free thoracic aortic rings of rats pre-contracted with PE. The mechanism of thoracic aortic rings dilation is endothelium-independent， which may be associated with receptor operational calcium channel，Ca2+-activated potassium channels and ATP-sensitive potassium channels.
ABSTRACT
Aim To investigate the effect of chronic intermittent hypobaric hypoxia ( CIHH) on the paeonol induced vasomotion of isolated rat ’ s thoracic aorta rings and its underlying mechanisms. Methods Spra-gue-Dawlay ( SD ) rats were randomly divided into 2 groups: control group ( CON ) and CIHH treatment group ( CIHH) . CIHH rats were exposed to hypoxia in a hypobaric chamber simulating 5 000 m altitude, 6 hours daily for 28 days. CON rats lived in the same en-vironment as CIHH animals except hypoxia. Organ bath technique was used to observe the effect of pae-onol on isolated thoracic aorta rings of rats. Results There were no significant differences of noradrenaline ( NE )- and KCl-induced contraction in thoracic aorta rings among CIHH and CON rats;CIHH enhanced va-sodilative effects of paeonol on isolated thoracic aorta rings of rats; the vasodilative effects on CIHH rats could be partly decreased by β-receptor blocker prop-ranolol,ATP-sensitive potassium channel ( KATP ) bloc-ker glibenclamide and NO synthase inhibitor L-NAME. Paeonol significantly inhibited NE-induced intracellular and extracellular calcium-dependent contraction in CIHH rats. Paeonol didn ’ t inhibit NE-induced con-traction by intracellular calcium release and its inhibi-tory effect couldn ’ t be blocked by glibenclamide in CON. Vasodilative effects of paeonol couldn ’ t be re-versed by indomethacin, a cyclooxygenase inhibitor, in CIHH and CON rats. Conclusion CIHH significantly enhances vasodilative effects of paeonol on isolated tho-racic aorta rings of rats. Besides promoting the signa-ling pathway of paeonol in CON, CIHH significantly enhances vasodilative effects of paeonol via activating KATP and inhibiting Ca2+ release from sarcoplasmic re-ticulum.
ABSTRACT
Objective To investigate the effect of specific cGMP-dependent protein kinase G (PKG) inhibitor (D)-DT-2 on the contractile function of rat vascular rings after being exposed to lipopolysaccharide (LPS).Methods The experiment was performed in 2 parts.Part Ⅰ:The Sprague-Dawley rat thoracic aortic rings were randomly divided into 3 groups (n =5 each):KH group,DT-2 group and (D)-DT-2 group.KH,DT-2 and (D)-DT-2 were added to the aortic ring after being dilated with 8-Br-cGMP 50 μmol/L for 25 min and the changes in tension of vascular rings were measured.Part Ⅱ:The rat thoracic aortic rings were randomly divided into 4 groups (n =5 each):control group,LPS group,LPS-DT2 group and LPS-(D)-DT2 group.After being incubated with LPS for 3 h in vitro.The Emax and EC50 were compared among the 4 groups.Results Part Ⅰ:Both DT-2 and (D)-DT-2 could contract the vascular rings dilated with 8-Br-cGMP and the Emax was significantly higher in (D)-DT-2 group than DT-2 group (P ＜0.05).Part Ⅱ]:Both DT-2 and (D)-DT-2 significantly improved the contractile function of vascular ring after being exposed to LPS.Emax was significantly higher,while EC50 was lower in groups DT-2 and (D)-DT-2 than in LPS group (P ＜0.01).Emax was significantly increased,while EC50 was decreased in LPS-(D)-DT-2 group as compared with LPS-DT-2 group (P ＜ 0.05).Conclusion PKG inhibitor can improve the contractile function of the vascular rings incubated with LPS and the efficacy of (D)-DT-2 is better than DT-2 in recovering the vascular reactivity.