Functional involvement of L-type calcium channels and cyclic nucleotide-dependent pathways in cadmium-induced myometrial relaxation in rats.

Modulation of myometrial spontaneity by cadmium (Cd) and its regulatory pathways was studied in rat uterus in the absence and presence of blockers of different signaling pathways. Isometric tension in myometrial strips, under a resting tension of 1 g, mounted in organ bath containing Ringer-Locke solution (RLS) continuously aerated with carbogen, was measured using data acquisition system-based physiograph and Lab Chart Pro V7.3.7 software. Mean integral tension was measured for 8 min. Cd (1 nM-0.1 mM) not only produced concentration-dependent inhibitory effect on rat myometrium but it (10 µM) also significantly ( p < 0.05) inhibited calcium chloride and BAY K-8644-induced myometrial contraction. Glybenclamide (10 µM), 4-aminopyridine (1 mM), and propranolol (10 µM) failed to significantly attenuate Cd-induced inhibitory responses, while L-NAME (0.1 mM), 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 25 µM), and 9-(tetrahydro-2-furanyl)-9H-purin-6-amine (SQ 22536; 1 µM) significantly ( p < 0.05) produced inhibitory effects on Cd-induced myometrial relaxation. Phenylephrine (1 nM-10 µM) and salbutamol (0.01 nM-0.1 µM)-induced relaxant effects on rat myometrium were significantly potentiated by 10 µM Cd. Thus based on the results of present functional study, it may be inferred that inhibitory effects of Cd on rat myometrium are mediated through blockade of L-type calcium channels and activation of NOS-NO-sGC and/or AC-cAMP pathways.

Anti-inflammatory activity of Dalbergia sissoo leaves.

The possible anti-inflammatory activity of the 90% ethanolic extract of Dalbergia sissoo leaves (DSELE) was studied in different models of inflammation in rats after oral administration at doses of 100, 300 and 1000 mg/kg. DSELE significantly inhibited carrageenin, kaolin and nystatin-induced paw oedema, as well as the weight of granuloma induced by a cotton pellet. It also inhibited dye leakage in acetic acid-induced vascular permeability test in mice. DSELE was devoid of ulcerogenic effect on the gastric mucosa of rats in acute and chronic tests. In acute toxicity studies, it was found to be safe up to 10.125 g/kg, p.o. in the rat. It was concluded that the D. sissoo leaf extract possessed significant anti-inflammatory activity (in acute, sub-acute and chronic models of inflammation) without any side effect on gastric mucosa.

Effect of centrally administered nitric oxide modulators in Brewer's yeast-induced nociception in rats.

Possible modulation of Brewer's yeast-induced nociception by centrally (icv) administered nitric oxide (NO) modulators, viz., NO synthase (NOS) inhibitors, NO precursor, donors, scavengers and co-administration of NO donor (SIN-1) with NOS inhibitor (L-NAME) and NO scavenger (Hb) was investigated in rats. Administration of NOS inhibitors and NO scavenger Hb increased the pain threshold capacity significantly, whereas NO donors SIN-1, SNP and NO precursor L-arginine were found to be hyperalgesic. D-arginine, the inactive isomer of L-arginine and methylene blue, inhibitor of soluble guanylate cyclase failed to alter the nociceptive behaviour in rats. Co-administration of SIN-1 with L-NAME and Hb found to increase the nociceptive threshold. The results indicate, that centrally administered NO modulators alter the nociceptive transmission induced by Brewer's yeast in rats.