Resveratrol did not alter blood pressure in rats with nitric oxide synthase-inhibited hypertension.

BACKGROUND: Inhibition of nitric oxide synthase (NOS) is a well-known experimental model of hypertension (HT). It was shown that oxidative stress contributes to the pathogenesis of HT. Resveratrol is a potent anti-oxidant that is found in red grapes, peanuts and red wine. It improves the NO response and increases endothelial NOS expression, which causes endothelium-dependent vasorelaxation as well as renal vasodilation. We aimed to explore the effects of resveratrol on blood pressure, the water-salt balance and sodium excretion as a reflection of renal function in NOS-inhibited rat models. METHODS: Thirty-five male Sprague-Dawley rats (200-250 g) were used in this study. In order to obtain hypertension models, an NOS inhibitor, N-nitro-L-arginin (L-NNA) was used. The rats were randomly divided into five groups: controls (given water and 0.8% salty diet) and four groups [given L-NNA, resveratrol (RSV) eluent, RSV, and L-NNA + RSV]. Blood pressures were measured indirectly by the tailcuff method on the first, seventh and 10th days. At the end of the study protocol (10th day), fluid balance, glomerular filtration rate, fractional sodium excretion, and blood and urine sodium and creatinine levels were measured. RESULTS: At the end of the study protocol, blood pressures were higher in only the L-NNA group (117.8 ± 3.5 vs 149.5 ± 2.1 mmHg; p < 0.05), as expected. Additional applications of RSV with L-NNA could not prevent the increase in blood pressure (122.8 ± 7.3 vs 155.4 ± 4.4 mmHg; p < 0.05). There were no remarkable changes in water-salt balance and renal function with the application of resveratrol. CONCLUSION: Resveratrol was unable to prevent or reverse blood pressure increase in NOS-inhibited rats.

The prevalence of VKORC1 1639 G>A and CYP2C9*2*3 genotypes in patients that requiring anticoagulant therapy in Turkish population.

The aim was to investigate the prevalence of VKORC1 and CYP2C9 genotypes in patients requiring anticoagulant therapy in two different region's populations of Turkey. The recent cohort included 292 patients that needed anticoagulant therapy, and who had a history of deep vein thrombosis and/or pulmonary artery thromboembolism. Genomic DNA was isolated from peripheral blood samples and the StripAssay reverse hybridization or Real Time PCR technique was used for genotype analysis. Genotypes for CYP2C9 were detected as follows: 165 (56.5 %) for CYP2C9*1/*1, 67 (23.0 %) for CYP2C9*1/*2, 25 (8.6 %) for CYP2C9*1/*3, 9 (3.0 %) for CYP2C9*2/*2, 21 (7.2 %) for CYP2C9*2/*3, 5(1.7 %) for CYP2C9*3/*3 for CYP2C9 and the allele frequencies were: 0.723 for allele*1, 0.182 for allele*2 and 0.095 for allele*3 respectively. Genotypes for VKORC1 were detected as follows: 64 (21.9 %) for GG, 220 (75.4 %) for GA and 8 (2.7 %) for AA alleles. The G allele frequency was detected as 0.596, and the A allele frequency was 0.404. The VKORC1 1639 G>A and CYP2C9 mutation prevalence and allele frequency of the current results from two different populations (Sivas and Canakkale) showed similarly very variable profiles when compared to the other results from the Turkish population.

Salt and nitric oxide inhibition induced hypertension: the role of prostacycline and 8-isoprostane.

Renal prostacycline (PGI(2)) and oxidative stress are known to be important factors that effect the natriurezis and diuresis. 8-iso prostaglandin F(2)α± (8-isoprostane), a member of F(2)-isoprostanes, is formed from the nonenzymatic reaction of arachidonic acid and oxygen radicals in vivo and in vitro, and also it is a marker of oxidative stress in vivo. The aim of this study is to determine the role of renal PGI(2) and 8-isoprostane in a salt and nitric oxide (NO) inhibition-induced hypertension model. Rats were distributed equally among four groups (n = 6 per group). Control rats were given normal salt diet (0.32%); high-salt (HS) rats were given high salt diet (3.2%); NG-nitro-L-arginine (L-NNA) rats were given normal salt diet and 25 mg/kg L-NNA; HS+L-NNA rats were given high salt diet and 25 mg/kg L-NNA. Rats were placed in individual metabolic cages for 17 days. Systolic blood pressure (SBP) was measured at days initial, 7th and 14th .Urinary 8-isoprostane and PGI(2) levels were analyzed. Salt- loading alone did not change SBP values. The average SBP in L-NNA and HS+L-NNA groups were shown to significantly enhance compared to initial and day 7th in the same groups, respectively. The levels of 8-isoprostane in the HS+L-NNA group was significantly enhanced compared to the other groups. L-NNA or HS diet alone did not change the levels of 8-isoprostane compared to the control group. L-NNA alone did not change PGI(2) levels in urine compared to the control. PGI(2) levels in the HS, and the HS+L-NNA group was significantly higher compared to the control group. This study concluded that NOS inhibition plus salt-loading induced oxidative stress and increased renal PGI(2). Also, it is suggested that augmented oxidative stress may aggravate the hypertension. But the renal synthesis of PGI(2) is increased in order to augment the diuresis and natriuresis without the effect of blood pressure (BP).

[Clonidine prevents development of hypertension in N (omega)-nitro-L-arginine-treated rats]. / Klonidin N (omega)-nitro-L-arjinin aracili hipertansiyon gelisimini önler.

OBJECTIVE: Although, there are some evidences on the contribution of increased sympathoadrenergic activity on long-term nitric oxide synthase (NOS) inhibition induced hypertension, the contribution of sympathetic activity to the development of this model of hypertension are not sufficiently studied. The aim of the present study is to investigate the effects of clonidine on blood pressure and vascular alpha-adrenergic receptors in the long-term N (omega)-nitro-L-arginine (L-NNA) treated rats. METHODS: Sixty two Wistar rats were randomly divided into 8 groups. All groups were administrated L-NNA and/or clonidine in two different concentrations for ten days. L-NNA was administrated in concentrations of 15 and 45 mg/100ml to L-NNA15 and L-NNA45 groups, respectively. Clonidine was also administrated in concentrations of 150 and 225 microg/100ml to KLO150 and KLO225 groups, respectively. Blood pressure and heart rates were measured with tail-cuff method and plasma NOx levels with spectrophotometer. The a-adrenoreceptors responses were evaluated in thoracic aorta rings in "in vitro" conditions. RESULTS: Clonidine prevented the L-NNA induced hypertension dose-dependently, but did not effect the heart rates decreased by L-NNA. The heart rates and blood pressure of normotensive rats were not changed by clonidine alone. Plasma NOx levels increased in L-NNA15 group (0.62+/-0.11 micromol/L, p=0.003) but did not change in other groups. The sensitivity of aorta to phenylephrine (-7.33+/-0.11 micromol/L, p=0.001) and clonidine (-7.60+/-0.27 micromol/L, p=0.003) in L-NNA45 group and phenylephrine (-6.94+/-0.13 micromol/L, p=0.002) in L-NNA15 group increased. The sensitivity of aorta to phenylephrine (7.93+/-0.16 micromol/L, p=0.001) in KLO225 group and to clonidine (-7.20+/-0.10 micromol/L, p=0.009) in KLO150 group increased. CONCLUSION: This study supports the idea suggesting that symphathetic nervous system activation is partly responsible for the development of the long-term NOS inhibition induced hypertension. In conclusion, it was shown for the first time that clonidine prevents the development of long-term NOS inhibition induced hypertension dose-dependently.

Nitric oxide synthase inhibition in rats: melatonin reduces blood pressure and ischemia/reperfusion-induced infarct size.

Reduction in the synthesis or bioavailability of nitric oxide plays a significant role in the development of myocardial infarction and hypertension. Numerous studies suggest that melatonin reduces blood pressure (BP) and ischemia/reperfusion (I/R) injury in rats. The effects of melatonin on the BP and I/R-induced cardiac infarct size in L-NAME-induced hypertensive rats remains unknown. This study was designed to investigate the effects of melatonin on BP and the I/R-induced infarct size in chronic nitric oxide synthase inhibited rats by L-NAME. Rats received L-NAME for 15 days to produce hypertension and melatonin the last 5 days before I/R studies. To produce cardiac damage, the left coronary artery was occluded for 30 min, followed by 120 min reperfusion. L-NAME led to a significant increase in BP. Melatonin administration (10 mg/kg) to L-NAME treated rats significantly reduced BP and infarct size. Also, melatonin attenuated the mortality resulting from I/R, but this was not statistically significant. Melatonin administration would seem important to reduce BP and infarct size resulting from I/R in L-NAME-induced hypertensive rats.

[Myocardial ischemia-reperfusion injury and melatonin]. / Miyokardiyal iskemi-reperfüzyon hasari ve melatonin.

It is believed that myocardial ischemia-reperfusion injury is related to increased free radical generated and intracellular calcium overload especially during the period of reperfusion. The pineal secretory product, melatonin, is known to be a potent free radical scavenger, antioxidant and can inhibit the intracellular calcium overload. In this review, we have summarized the fundamental of cardiac ischemia-reperfusion injury and the effects of melatonin on myocardial damage that related to cardiac ischemia-reperfusion injury. The total antioxidant capacity of human serum is related to melatonin levels. Incidence of sudden cardiac death is high in the morning hours. It has been shown that melatonin levels are significantly low at these times and patients with coronary heart disease have lower than normal individuals. These findings thought that melatonin would be valuable to test in clinical trials for prevention of possible ischemia-reperfusion-induced injury, especially life threatening arrhythmias and infarct size, effecting life quality, associated with thrombolysis, angioplasty, coronary artery spasm or coronary bypass surgery.