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In the present study, the free vibration of functionally graded graphene platelet‐reinforced (FG‐GPLs) and functionally graded carbon nanotube‐reinforced (FG‐CNTs) hybrid laminated nanocomposite truncated conical shells and panels are analyzed. Multi‐layers truncated conical shell and panel of pure FG‐CNTs, pure FG‐GPLs and hybrid CNTs‐GPLs reinforcement were evaluated. In light of its high accuracy in the calculation of thin and thick shells, a third‐order shear deformation theory is adopted. The governing equations and boundary conditions is derived using Hamilton's principle and is solved numerically using the systematic differential quadrature method (DQM) which uses Kronecker delta function. The effective mechanical properties of the CNT‐reinforced nanocomposite layers are estimated using the rule of mixtures, whereas those of the GPL‐reinforced nanocomposite layers is calculated using the Halpin‐Tsai micromechanical model. Convergence and accuracy evaluation of the presented study are confirmed and a number of parameters, including the CNTS volume fraction, GPLs mass fraction, distribution patterns (i.e., Uniform distribution (UD), Functionally graded O‐distribution (FG‐O), Functionally graded X‐distribution (FG‐X), Functionally graded V‐distribution (FG‐V) and FG‐A), different boundary conditions and the vertex angle of the cone, are investigated. The results obtained in this article for the combination of two different materials, GPLs and CNTs, showed that in controlling the natural frequency of the system, without changing the percentage of fiber and only by changing the arrangement, very wonderful results can be achieved. [ABSTRACT FROM AUTHOR]

Background/Aims: Acute cholestasis is associated with cardiovascular complications. The purpose of the present study was to investigate the effect of cholestasis on heart apoptosis and the involvement of nitric oxide (NO) and oxidative stress in the possible altered apoptosis of cholestatic hearts. Methods: Cholestasis was induced by bile duct–ligation, and sham-operated mice served as controls. Three days after the surgery, heart tissues were evaluated for apoptosis and the level of malondialdehyde (MDA), and the activities of catalase (CAT), glutathione peroxidase (GSHPx) and superoxide dismutase (SOD) have been studied in cardiac tissues. The role of treatment withl-NAME, a non-selective inhibitor of NO synthase, or withd-NAME, an inactive isomer ofl-NAME, on cholestatic and sham cardiac apoptosis, level of MDA and CAT, SOD and GSHPx activities was also investigated. The content of NO in cardiac tissue was also determined. Results: Cholestatic hearts showed structural abnormalities and increased apoptosis compared with sham hearts. Treatment withl-NAME, but notd-NAME, improved both structural abnormalities and enhanced apoptosis of cholestatic hearts. Cholestatic hearts also had an increased level of MDA and decreased activities of CAT and GSHPx, which were not modified byd-NAME treatment. Byl-NAME treatment, the level of MDA decreased and activities of CAT, GSHPx and SOD increased in BDL mice. The content of NO was higher in cholestatic cardiac tissue, which was decreased byl-NAME treatment. Conclusion: In conclusion, apoptosis in cholestatic heart might have occurred because of NO overproduction, which could induce oxidative stress in the heart of cholestatic mice. [ABSTRACT FROM AUTHOR]

OBJECTIVE To verify the effect of chronic lithium administration on the endothelium-dependent relaxation of rat corpus cavernosum, as lithium is a major drug for treating bipolar disorder and some studies showed that lithium might cause erectile dysfunction in such patients, by a mechanism as yet unknown. MATERIALS AND METHODS LiCl (600 mg/L) was dissolved in drinking water and Sprague–Dawley rats received the solution for 30 days; control rats received tap water. After 30 days corporeal strips were prepared from both groups, mounted under tension in oxygenated organ baths, and pre-contracted with phenylephrine (7.5 µm). After equilibration, the strips were relaxed by acetylcholine (10 nm to 1 mm) in the presence or absence of indomethacin (a cyclooxygenase inhibitor; 20 µm). Furthermore, the relaxant responses to sodium nitroprusside (1 nm to 1 mm), a nitric oxide (NO) donor, were investigated in both groups. NADPH-diaphorase histochemistry was used to identify NO synthase within cavernosal tissue strips of both groups. RESULTS The acetylcholine-dependent relaxation was significantly lower in lithium-treated rats than in controls. Although indomethacin decreased significantly the relaxant responses to acetylcholine in controls, it increased the relaxant responses in lithium-treated rats. NADPH-diaphorase staining was greater in the chronic lithium-treated than in control preparations. Sodium nitroprusside produced similar relaxation in both groups. CONCLUSION Chronic lithium administration can impair the endothelium-dependent relaxation of rat corpus cavernosum; NO availability might decrease after lithium administration and the cyclooxygenase pathways might have a role in this effect. [ABSTRACT FROM AUTHOR]

It is well known that chronotropic and inotropic responses to β-adrenergic stimulation are impaired in cirrhosis, but the exact reason is not clear. Considering the inhibitory effect of endogenous opioid peptides and nitric oxide (NO) on β-adrenergic pathway, we examined their roles in hyporesponsiveness of isolated atria and papillary muscles to isoproterenol stimulation in cirrhotic rats. Cirrhosis was induced by chronic bile duct ligation. Four weeks after ligation or sham operation, the responses of the isolated atria and papillary muscles to isoproterenol stimulation were evaluated in the absence and presence of naltrexone HCl (10−6 m), N( ω)-nitro-l-arginine methyl ester (l-NAME, 10−4 m), and naltrexone plusl-NAME in the organ bath. Considering the role of inducible NOS (iNOS) in hemodynamic abnormalities of cirrhotic rats, the chronotropic and inotropic responses of cirrhotic rats to isoproterenol stimulation were also assessed in the presence of aminoguanidine (a selective inhibitor of iNOS, 3 × 10−4 m). Sham operation had no significant effect on basal atrial beating rate, contractile force, and maximal time derivatives for the development and the dissipation of papillary muscle tension. The basal atrial beating rate of cirrhotic rats did not show any significant difference compared with the sham-operated ones; however, the basal contractile parameters were significantly decreased in cirrhosis. Although the maximum effects of isoproterenol on chronotropic and inotropic responses were significantly reduced in cirrhotic rats, there was no difference in half-maximal effective concentrations of isoproterenol in these concentration–response curves. The basal abnormalities and the attenuated chronotropic and inotropic responses to isoproterenol were completely corrected by the administration of naltrexone,l-NAME and aminoguanidine. Concurrent administration of naltrexone andl-NAME also restored to normal the basal abnormalities and the blunted responses to isoproterenol in cirrhotic rats, and did not show any antagonistic effect. Based on these findings, both the endogenous opioid peptides and NO may be involved in the attenuated chronotropic and inotropic responses to β-adrenergic stimulation in cirrhosis. It seems that the iNOS activity results in NO-induced hyporesponsiveness to β-adrenergic stimulation in cirrhosis. [ABSTRACT FROM AUTHOR]

Recent evidence indicates that sildenafil may exert some central effects through enhancement of nitric oxide (NO)-mediated effects. NO is known to have modulatory effects on seizure threshold, raising the possibility that sildenafil may alter seizure susceptibility through NO-mediated mechanisms. This study was performed to examine whether sildenafil influences the threshold of clonic and/or generalized tonic seizures through modulation of nitric oxide (NO)–cGMP pathway.The effect of sildenafil (1–40 mg kg−1) was investigated on clonic seizures induced by intravenous administration of GABA antagonists pentylenetetrazole (PTZ) and bicuculine and on generalized tonic seizures induced by intraperitoneal administration of high dose PTZ in male Swiss mice. The interaction of sildenafil-induced effects with NO–cGMP pathway was examined using nitric oxide synthase (NOS) inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), NOS substrate L-arginine, NO donor, sodium nitroprusside (SNP) and guanylyl cyclase inhibitor methylene blue (MB).Sildenafil induced a dose-dependent proconvulsant effect in both models of clonic, but not generalized tonic type of seizures. Pretreatment with either MB or L-NAME inhibited the proconvulsant effect of sildenafil, indicating the mediation of this effect by NO–cGMP pathway. In addition, a subeffective dose of sildenafil induced an additive proconvulsant effect when combined with either L-arginine or SNP.Sildenafil induces a proconvulsant effect on clonic seizure threshold that interacts with both exogenously and endogenously released NO and may be linked to activation of NO–cGMP pathway.British Journal of Pharmacology (2006) 147, 935–943. doi:10.1038/sj.bjp.0706680; published online 6 February 2006 [ABSTRACT FROM AUTHOR]