Nebivolol prevents remodeling in a rat myocardial infarction model: an echocardiographic study.

OBJECTIVE: Ventricular remodeling (VR) which develops after myocardial infarction (MI) plays an important role in progressive left ventricular dysfunction. We aimed to investigate the role of nebivolol treatment on VR after a MI in a rat ischemia-reperfusion model. METHODS: Rats were divided into 3 groups of 12 each: sham operated (sham-control), MI-induced (MI-control) and nebivolol treated (MI-nebivolol). Left ventricular (LV) diameters, volumes, and diastolic filling parameters were evaluated by echocardiography. On the 28th day, after recording the systemic and LV pressures and determining the plasma nitric oxide (NO) and peroxynitrite (ONOO-) levels , animals were sacrificed and heart, body and LV weights (HW, BW, LVW) were measured and infarct sizes were determined. Results were evaluated statistically by ANOVA for repeated measurements 3x3 factorial design with post-hoc Bonferroni test. RESULTS: After MI, while VR (an increase in LV diameters and volumes associated with a decrease in EF, FS and posterior wall thickness change (LWPc) was significant in MI-control rats (p<0.05 for; all comparisons) these changes were significantly less in MI-nebivolol group (p=0.08 and p=0.06 for EF and FS respectively). LV end diastolic pressure (LVEDP) was lower (p<0.005) and Delta+/- dp/dt's (p<0.05) were higher in MI-nebivolol group compared to MI-control animals. Although infarct sizes were similar in MI-induced groups (p=0.79); LVW/HW and HW/BW's were significantly greater in the MI-control group compared to sham-control (p<0.01 for all comparisons), these changes were not statistically significant in MI-nebivolol group. The increase in plasma NO and ONOO- levels were also prevented with nebivolol. CONCLUSION: Nebivolol therapy reduced the effects of VR in rats after MI. These beneficial effects were not related to its heart rate and blood pressure reducing effects. Nitric oxide regulatory action of this compound may contribute these beneficial effects on VR developed after MI.

Synthesis and evaluation of analgesic, anti-inflammatory and antioxidant activities of new 6-acyl-3-alkyl-5-methyl-2(3H)-benzoxazolones.

A new series of 6-acyl-3-alkyl-5-methyl-2(3H)-benzoxazolones have been obtained starting from 5-methyl-2(3H)-benzoxazolone. All the compounds have been characterized by IR, 1H-NMR and mass spectroscopy. The new compounds were screened for analgesic and anti-inflammatory activities and ulcerogenic effect. The in vitro antioxidant capacity of the synthesized compounds were tested by the nitric oxide radical scavenging assay. Most of the compounds showed antiinflammatory activity. Among them, 3-[4-(4-fluorophenyl)piperazinomethyl] -6-(3-chlorobenzoyl)-5-methyl-2(3H)-benzoxazolone (3j) was found more potent than the reference drug indometacin (CAS 53-86-1) with 41.66% decrease in edema. Compared with the control, some of the compounds exhibited analgesic effects. Similar to the anti-inflammatory activity results, compound 3j showed the highest analgesic profile with 48.56% inhibition. No active hemorragic focus was observed in the microscopic evaluation in the ulcerogenic effect studies of the tested compounds. 6-(3-Chlorobenzoyl)-5-methyl-2(3H)-benzoxazolone (2b) and 3-[4-(4-fluorophenyl-piperazino)methyl]-6-(3-chlorobenzoyl)-5-methyl-2(3H)-benzoxazolone (3j) showed nearly maximum antioxidant activity compared to ascorbic acid (CAS 50-81-7) with IC50 values of 27.6 and 30.1 microg/mL, respectively.