[Effect of endogenous nitric oxide on cardiac ischemic preconditioning in rat]

Ischemic Preconditioning [IPC] is the phenomen that happens on the heart by one or several short periods of ischemia followed by reperfusion that improve the postischemic recovery of mechanical function. Ischemic preconditioning [IPC] may protect the heart from ischemia reperfusion injury by nitric oxide formation. This study investigated the effect of ischemic preconditioning on heart and the relationship between nitric oxide. 28 male Sprague dawley rats [200-250 g] in Tehran University of Medical Sciences were used. Rats were anesthetized and hearts were rapidly isolated and perfused in the Langendorff mode at a constant perfusion pressure and temperature of 37°C. hearts were divided to 4 groups. Control group was perfused 170 minutes with buffer solution. ischemic reperfusion [IR] group was subjected to 30 minutes ischemia. [Ischemic preconditioning] IPC group was elicited by 5 min ischemia followed 5 min reperfusion before IR and L-NAME + IPC group, L-NAME [0.1mM] was added into the perfusion solution. Heart rate [HR], left ventricular development [LVDP], RPP [LVDPXHR], infarct size and coronary flow [CF] were measured. ANOVA tests[with TUKEY post test if p<0.05] were used for statistical analyses. IPC improve the postischemic recovery and reduced postischemic ventricular dysfunction in heart and reduction of infarction size. No significant differences were observed between IPC and IPC + L-NAME groups. L-NAME did not affect postischemic recovery of IPC so in the isolated heart NO isn't involved in the cardioprotective effect of IPC

Effect of biliary cirrhosis on nonadrenergic noncholinergic-mediated relaxation of rat corpus cavernosum: Role of nitric oxide pathway and endocannabinoid system

Relaxation of the corpus cavernosum plays a major role in penile erection. Nitric oxide [NO] is known to be the most important factor mediating relaxation of corpus cavernosum, which is mainly derived from nonadrenergic noncholinergic [NANC] nerves. The aim of the present study was to investigate the effect of biliary cirrhosis on nonadrenergic noncholinergic [NANC]-mediated relaxation of rat corpus cavernosum as well as the possible relevant roles of endocannabinoid and nitric oxide systems. Corporal strips from sham-operated and biliary cirrhotic rats were mounted under tension in a standard oxygenated organ bath with guanethidine sulfate [5 micro M] and atropine [1 micro M] to induce adrenergic and cholinergic blockade. The strips were precontracted with phenylephrine hydrochloride [7.5 micro M] and electrical field stimulation was applied at different frequencies [2, 5, 10, 15 Hz] to obtain NANC-mediated relaxation. In separate precontracted strips of the sham and cirrhotic groups, the concentration-dependent relaxant responses to sodium nitroprusside [10 nM-1mM], as an NO donor, were assessed. The NANC-mediated relaxation was significantly enhanced in cirrhotic animals [P < 0.01]. Anandamide potentiated the relaxations in both groups [P < 0.05]. The cannabinoid CB1 receptor antagonist AM251 [10 micro M] and the vanilloid receptor antagonist capsazepine [10 micro M] each significantly prevented the enhanced relaxations in cirrhotic rats [P < 0.01]. The CB2 receptor antagonist AM630 had no effect on relaxations in the cirrhotic group. In a concentration-dependent manner, L-NAME [30-1000 nM] inhibited relaxations in both the sham and cirrhotic groups, although cirrhotic groups were more resistant to the inhibitory effects of L-NAME. The degree of relaxation induced by sodium nitroprusside [10 nM-1 mM] was similar in the two groups. Biliary cirrhosis enhances the neurogenic relaxation in rat corpus cavernosum probably via the NO pathway and cannabinoid CB1 and vanilloid VR1 receptors

Effects of glycyrrhiza derivatives against acetaminophen-induced hepatotoxicity

Glycyrrhyzin, extracted from the roots of licorice [Glycyrrhiza glabra] and its aglycone [glycyrrhetinic acid] exhibit various anti-inflammatory, anti-allergic, anti-gastric ulcer, anti-hepatitis and anti-hepatotoxic activities. It has been shown that glycyrrhiza derivatives have antihepatotoxic activity and protect against carbon tetrachloride and D-galactosamine induced acute liver injury and cirrhosis. Methods The influences of glycyrrhiza derivatives such as deglycyrrhizined licorice [DGL], glycyrrhetinic acid monohemiphthalate disodium [GAMHPH] and high glycyrrhizinised licorice [HGL] on acetaminophen induced liver damage was studied in male Sprague-Dawley rats. The rats were given a single dose of these derivatives [200 mg/kg, ip] 2 hours before ip injection of acetaminophen toxic dose [750 mg/kg]. Liver damage was assessed by transmission electron microscopic examination and measurements of serum hepatic transaminase enzymes performed 6 hours after treatment with acetaminophen. All glycyrrhiza derivatives prevented acetaminophen induced hepatotoxicity, as reflected by decreased level of serum transaminases and lesser degree of hepatic necrosis. Action of glycyrrhizin and its analogues as antioxidants and their ability to disturb intracellular calcium in hepatic cells, are possible mechanisms of their protective effects on acetaminophen-induced hepatotoxicity. Glycyrrhiza derivatives must be taken into account as protective agents in hepatotoxicity when large doses of acetaminophen must be used for longer period of time