Parabiosis Improves Endothelial Dysfunction in Aged Female Mice.

INTRODUCTION: The study aims to investigate the effect of parabiosis method on endothelial dysfunction in naturally aging mice and determine the time projections for predicted improvement in the mentioned target group. METHODS: The balb/c mice were separated into six groups, these being; isochronic old, heterochronic old (HP-O), isochronic young, heterochronic young, young control, and old control. After parabiosis protocol, animals were sacrificed at the third, fifth, seventh, and ninth weeks, and their thoracic aortas were isolated. The vasodilatation and vasoconstriction responses of the vessels were detected using potassium chloride and phenylephrine, acetylcholine (ACh), and sodium nitroprusside. RESULTS: Aging had a significant decreasing effect on maximum ACh relaxation responses (P < 0.01). However, in the HP-O group, the maximum ACh relaxation response in the third week was significantly lower (P < 0.05), but this effect disappeared in the ninth week. Maximum phenylephrine contraction responses were lower in the heterochronic parabiosis group (P < 0.05). CONCLUSIONS: ACh responses increased at the end of the ninth week in the HP-O group, therefore, the parabiosis model may have an improving effect on endothelial dysfunction seen in aging.

The contribution of carbon monoxide to vascular tonus.

OBJECTIVE: The aim of this descriptive study was to examine the contribution of CO in the maintenance of vascular tonus in different organs and different vessel segments; the underlying mechanism of CO-induced vasodilation was investigated. METHODS: Sixty Wistar albino rats, aged 6-8 months, were used in this study. Response to CO by isolated arteries from the thoracic and abdominal aorta and mesenteric, renal, gastrocnemius, and gracilis muscles as well as heart, lung, and brain vascular beds was endogenously and exogenously studied using organ baths or myograph. In addition, HO-2 protein expression was assessed using Western blot analysis in isolated vessel segments. RESULTS: Although CO was shown to contribute to the regulation of vascular tonus in all feed arteries except those of the gracilis vascular bed, no effect was observed in the resistance arteries, with the sole exception of the pial artery. No relationship between HO-2 protein level and CO contribution to endogenous vascular tonus was observed. CONCLUSIONS: While the vasodilator effect of CO in vessels smaller than 600 µm in diameter was found to be mediated via potassium channels, in vessels larger than 600 µm in diameter, the effect was through both the potassium channels and the cGMP pathway.

Effect of 20-HETE inhibition on L-NAME-induced hypertension in rats.

20-Hydroxyeicosatetraenoicacid (20-HETE) is an important mediator that regulates vascular tone and blood pressure (BP). Although various experimental animal hypertension models demonstrated that 20-HETE contributes to increased vascular resistance and BP, these effects have not been studied in Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced hypertension model. In this study, we investigated the effects of 20-HETE on the vascular responsiveness and BP in an L-NAME-induced hypertension. Wistar Albino rats were used in this study. Hypertension was induced by the addition of L-NAME to drinking water for 5 weeks. The study was performed in three stages: first, BP changes were monitored in real time in the presence of 20-HETE enzymatic inhibitor, N-hydroxy-N´-(4-butly-2-methylphenyl)-formamidine (HET-0016) for 1 h. Second, vascular responses of the conduit and resistance arteries were investigated in the presence or absence of HET-0016 in the organ bath. Third, BP was monitored weekly in some hypertensive animals treated with HET-0016 and vascular responses were investigated at the end of the experiment. We demonstrated an increase in 20-HETE levels in the resistance arteries of hypertensive animals. 20-HETE inhibition by HET-0016 significantly decreased BP in L-NAME-induced hypertension model. In addition, HET-0016 treatment caused significant improvement in vascular dilator and constrictor responses in the conduit and resistance arteries. This study demonstrates an important role of 20-HETE in increasing BP and altering vascular responsiveness in L-NAME-induced hypertension model, which suggests a possible involvement of 20-HETE in essential hypertension development in humans.

The Effect of Magnesium on Visual Evoked Potentials in L-NAME-Induced Hypertensive Rats.

In the literature, although there are many studies regarding complications of hypertension, information concerning its influence on visual evoked potentials (VEPs) is limited. This study aims to clarify the possible therapeutic effects of the preferential magnesium (Mg) treatment on VEPs in an experimental hypertension model. Rats were divided into four groups as follows: control, Mg treated (Mg), N(omega)-nitro-L-arginine methyl ester (L-NAME) hypertension, and L-NAME hypertension + Mg treated (L-NAME + Mg). Hypertension was induced by L-NAME which was given to rats orally over 6 weeks (25 mg/kg/day in drinking water). A magnesium-enriched diet (0.8 g/kg) was given to treatment groups for 6 weeks. Systolic blood pressure (SBP) was determined by using the tail-cuff method. Flash VEPs were recorded. Our results revealed that the SBP was significantly increased in the L-NAME group compared to control. Magnesium treatment significantly attenuated SBP in the hypertensive rats compared to the L-NAME group. The mean latencies of P1, N1, P2, N2, and P3 components were significantly prolonged in hypertensive rats compared to control. Treatment with Mg provided a significant decrease in the latencies of P1, N1, P2, N2, and P3 potentials in the L-NAME + Mg group compared to the L-NAME group. Plasma Mg levels were increased in the L-NAME + Mg group compared to the L-NAME group. No change was detected in the Mg levels of the brains in all experimental groups. Magnesium treatment had no effect on the brain nitrate/nitrite and thiobarbituric acid-reactive substances (TBARS) levels in hypertensive rats compared to non-treated rats. There was a positive correlation between the brain TBARS levels and SBP of the rats. The present study suggests that Mg supplementation has the potential to prevent VEP changes in the L-NAME-induced hypertension model.

Effect of magnesium on vascular reactivity in NOS inhibition-induced hypertension.

This study investigated the effect of magnesium on the vascular reactivity of conduit and resistance arteries in a nitric oxide synthase inhibition-induced hypertension model. The aorta and third-order branches of the mesenteric artery were dissected from normotensive control and hypertensive rats, and their constriction and dilation responses in physiological saline solution containing normal (1.2 mM) or high (4.8 mM) magnesium concentrations were examined. The responses of the vessels were evaluated using potassium chloride (KCl) and phenylephrine (Phe), acetylcholine (ACh) and sodium nitroprusside. The Phe-induced constriction response of the aortic rings increased, whereas the ACh-induced dilation response decreased, in the hypertensive group compared to controls, in the presence of a normal magnesium concentration. High magnesium did not alter these responses in either group. Both the KCl- and Phe-induced constriction responses of the mesenteric arteries increased, and the ACh-induced dilation response decreased in the hypertensive group compared to controls, in the presence of a normal magnesium concentration. High magnesium significantly decreased the KCl and Phe-induced constriction and increased the ACh-induced dilation response of the mesenteric arteries in the hypertensive group, while it did not alter these responses in controls. This study suggests that high magnesium improves vascular reactivity of resistance-, but not conduit-type arteries in the nitric oxide synthase inhibition-induced hypertension model.

Effect of magnesium supplementation on blood pressure and vascular reactivity in nitric oxide synthase inhibition-induced hypertension model.

The aim of this study was to assess the effect of oral magnesium supplementation (Mg-supp) on blood pressure (BP) and possible mechanism in nitric oxide synthase (NOS) inhibition-induced hypertension model. Hypertension and/or Mg-supp were created by N-nitro-l-arginine methyl ester (25 mg/kg/day by drinking water) and magnesium-oxide (0.8% by diet) for 6 weeks. Systolic BP was measured weekly by tail-cuff method. The effects of hypertension and/or Mg-supp in thoracic aorta and third branch of mesenteric artery constriction and relaxation responses were evaluated. NOS-inhibition produced a gradually developing hypertension and the magnitude of the BP was significantly attenuated after five weeks of Mg-supp. The increased phenylephrine-induced contractile and decreased acetylcholine (ACh)-induced dilation responses were found in both artery segments of hypertensive groups. Mg-supp was restored ACh-relaxation response in both arterial segments and also Phe-constriction response in thoracic aorta but not in mesenteric arteries. The contributions of NO, prostaglandins and K(+) channels to the dilator response of ACh were similar in the aorta of all the groups. The contribution of the NO to the ACh-mediated relaxation response of mesenteric arteries was suppressed in hypertensive rats, whereas this was corrected by Mg-supp. The flow-mediated dilation response of mesenteric arteries in hypertensive rats failed and could not be corrected by Mg-supp. Whereas, vascular eNOS protein and magnesium levels were not changed and plasma nitrite levels were reduced in hypertensive rats. The results of this study showed that Mg-supp lowered the arterial BP in NOS-inhibition induced hypertension model by restoring the agonist-induced relaxation response of the arteries.