M. Alvarez de Sotomayor

Effects of chronic treatment with simvastatin on endothelial dysfunction in spontaneously hypertensive rats.

OBJECTIVE To investigate the effects of chronic treatment with simvastatin (SV) on endothelium-dependent relaxation and ouabain-induced contractions in aortic rings from spontaneously hypertensive rats (SHR), comparing with normotensive Wistar-Kyoto rats (WKY). METHODS After a 12-week period of administration of 1 or 2 mg/kg SV to SHR and WKY, systolic blood pressure (SBP) and vascular reactivity in endothelium-intact aortic rings were assessed. RESULTS Relaxation in response to acetylcholine (ACh) in WKY remained unaltered, but in SHR treated with 1 mg/kg SV, enhanced ACh-induced relaxation (P<0.05 versus untreated SHR) reached values observed in untreated WKY. The 2 mg/kg treatment also improved ACh relaxation (P<0.01 and P<0.05 versus untreated SHR and WKY respectively). Inhibiting cyclo-oxygenase (COX) with indomethacin (INDO) improved ACh relaxation in SHR (P<0.05) but not in WKY, independent of treatment with SV. Inhibition of nitric oxide synthase (NOS) with N(G)-nitro-L-arginine (L-NOARG) abolished ACh relaxations in all cases (P<0.001). The result was unaltered when combining INDO plus L-NOARG. SV treatment also decreased ouabain-induced contractions in endothelium-intact aortic rings from SHR, diminishing the percentage effect of contraction from 64.56+/-2.95 (untreated SHR) to 26.98+/-7.06 and 38.10+/-8.21 (1 and 2 mg/kg treated SHR respectively). Response to ouabain in WKY was not significantly affected by SV treatment CONCLUSIONS Chronic treatment of SHR with SV improves endothelium-dependent ACh relaxation of the aortic rings, probably by an NO-involving mechanism more than by inhibiting contractile COX-derived factors. An improvement in endothelial modulation of ouabain-induced contractions was also observed after treatment with SV in SHR, which might be due to an inhibition of a calcium-sodium exchanger.

Uterine relaxant effect of zolpidem: a comparison with other smooth muscle relaxants.

Zolpidem is an imidazopyridine sedative-hypnotic which interacts with central benzodiazepine- receptors. To examine its effects on uterine smooth muscle we have compared with those obtained by diltiazem, papaverine and diazepam on different experimental models. The IC50 values obtained indicate similar behaviour of zolpidem and diazepam. They showed more active against the spontaneous contractions and those induced by KCl (60 mᴍ) or by CaCl2 (0.01-10 mᴍ) in Ca2+-free depolarizing medium than against acetylcholine (0.1 mᴍ)-induced contractions. Both of them also showed more effectiveness against the tonic component of the acetylcholine-evoked contraction than against the phasic one. All the drugs tested were less powerful against contractions induced by oxytocin than against those induced by other agonists. This observation let us speculate that the mechanism of action of zolpidem may be related to an action on Ca2+ influx through voltage-dependent Ca2+ channels due to an interaction with low affinity receptor located at the plasmalemma as has been suggested for diazepam