Effect of oral sirolimus therapy on inflammatory biomarkers following coronary stenting

We studied the effect of oral sirolimus, administered to prevent and treat in-stent restenosis (ISR), on the variation of serum levels of inflammatory markers following coronary stenting with bare metal stents. The mean age of the patients was 56 ± 13 years, 65 percent were males and all had clinically manifested ischemia. Serum levels of high sensitivity C-reactive protein (hs-CRP) concentration were determined by chemiluminescence and serum levels of all other biomarkers by ELISA. One group of patients at high risk for ISR received a loading oral dose of 15 mg sirolimus and 5 mg daily thereafter for 28 days after stenting (SIR-G). A control group (CONT-G) was submitted to stenting without sirolimus therapy. The increase in hs-CRP concentration was highest at 24 h after stenting in both groups. A significant difference between SIR-G and CONT-G was observed at 4 weeks (-1.50 ± 5.0 vs -0.19 ± 0.4, P = 0.008) and lost significance 1 month after sirolimus discontinuation (-1.73 ± 4.3 vs -0.01 ± 0.7, P = 0.0975). A continuous fall in MMP-9 concentration was observed in SIR-G, with the greatest reduction at 4 weeks (-352.9 ± 455 vs +395.2 ± 377, P = 0.0004), while a positive variation was noted 4 weeks after sirolimus discontinuation (227 ± 708 vs 406.2 ± 472.1, P = 0.0958). SIR-G exhibited a higher increase in P-selectin after sirolimus discontinuation at week 8 (46.1 ± 67.9 vs 5.8 ± 23.7, P = 0.0025). These findings suggest that the anti-restenotic actions of systemic sirolimus include anti-proliferative effects and modulation of the inflammatory response with inhibition of adhesion molecule expression.

Effect of age and magnesium administration on the performance of SHR in the elevated plus-maze

It is currently accepted that young spontaneously hypertensive rats (SHR) have lower pressure levels than adult SHR in which the hypertension is well established, reaching the highest plateau at about 24 weeks, and that treatment with magnesium initiated during intrauterine life postpones the onset of cardiovascular alterations in SHR to about 90 days. These animals also show many behavioral alterations. The anxiety of SHR was measured in the elevated plus-maze, considering the age of the animals and previous ingestion of food supplemented with 1 percent magnesium oxide. Both young (1.5-2 months) and adult (5-6 months) SHR showed higher mean) (+ or - SEM) percent of entries (48 + or - 3 and 51 + or - 3, respectvely) and a longer mean (+ or - SEM) percent of time spent (43 + or - 5 and 55 + or - 5, respectively) in the open arms when compared to the mean (+ or - SEM) percent of entries and time spent in the open arms of young (35 + or - 3 and 20 + or - 4, respectively) and adult (36 + or - 7 and 17 + or - 5, respectively) normotensive Wistar rats. Treatment with magnesium oxide did not alter the performance of SHR in the elevated plus-maze. SHR showed an anxiolytic-like behavior which was neither influenced by age nor by antihypertensive treatment

Effects of the antihypertensive drugs Ó-methyldopa and hydralazine on the performance of spontaneously hypertensive rats in the elevated plus-maze

The effects of antihypertensive drugs on the performance of spontaneously hypertensive rats (SHR) in the elevated plus-maze were determined. Male SHR (3 months old) were submitted to long-term treatment (15 days) with Ó-methyldopa (ÓMD, 5g/l, N = 10) and hydralazine (HYD, 100 mg/l, N = 10) given orally, diluted in water. After the drug treatment, the performance of the rats in the plus-maze was observed for 5 min in a single test and mean arterial pressure (MAP) and heart rate (HR) were then measured. The antihypertensive drugs reduced MAP significantly (mean ñ SEM:CON = 176.2 ñ 5.2, ÓMD = 157.8 ñ 4.6 and HYD = 150 ñ 4.4 mmHg) and only ÓMD increased HR significantly (mean ñ SEM:CON = 391.7 ñ 13.8, ÓMD = 453.3 ñ 14 and HYD = 368.8 ñ 18.9 bpm). The ÓMD group presented a lower total number of entries (mean ñ SEM:CON = 12.7 ñ 0.7, ÓMD = 8.7 ñ 0.9 and HYD = 12 ñ 0.9) and spent less time in the open arms than the CON (N = 10) and HYD groups (mean ñ SEM:CON = 0.69 ñ 0.04, ÓMD = 0.48 ñ 0.07 and HYD = 0.65 ñ 0.06 s). ÓMethyldopa acts centrally and hydralazine acts peripherally. The behavioral change of SHR treated with Ó-methyldopa suggests that hypertension seems to be related to central nervous dysfunctions that are affected by an antihypertensive drug with central noradrenergic action