Plasma Concentrations Of Nitric Oxide Metabolites Research Articles

A high single oral dose of turmeric extract (Curcuma longa L.) does not improve skeletal muscle microvascular reactivity in older subjects

Increased production of reactive oxygen species reduces nitric oxide (NO) bioavailability and impairs vascular function with aging. Curcumin is a polyphenolic compound found in the rhizome of turmeric (Curcuma longa) with antioxidant properties. An increasing number of studies have demonstrated improvement in the vasodilatory response of conduit arteries following curcumin supplementation, which has been associated with increased NO production. However, less is known about the effects of curcumin on resistance vessels response. Therefore, the present study aimed to investigate the effects of a high single dose of turmeric extract on skeletal muscle microvascular reactivity and plasma concentrations of NO metabolites in older adults. Twenty-one older adults consumed 10 g of turmeric extract (CUR) or placebo (PLA) in a randomized, double-blind, and crossover design. Blood samples were drawn to assay NO metabolites (NO2− and NO3−), and changes in oxygen saturation parameters following arterial occlusion were used to evaluate microvascular reactivity. There were no significant changes in plasma concentrations of NO2− and NO3− as well the parameters of oxygen saturation were not affected after CUR. In conclusion, a high single dose of turmeric extract does not affect the plasma concentration of NO metabolites nor skeletal muscle microvascular reactivity in older adults.

Nitric Oxide Metabolism in Adults With Cyanotic Congenital Heart Disease

Endothelial-derived nitric oxide (NO) diffuses abluminally to regulate blood flow by activating soluble guanylate cyclase in medial smooth muscle. However, a significant fraction of NO diffuses luminally, where the extremely high reaction rate with red blood cell hemoglobin (Hb) effectively reduces luminal concentration to zero. The erythrocytosis of cyanotic congenital heart disease has potentially opposing effects, namely, a reduction in medial smooth muscle NO bioavailability because of the increase in luminal consumption of the molecule and, conversely, an increase in the elaboration of NO in response to the high endothelial shear stress of the erythrocytotic perfusate. NO metabolism in cyanotic congenital heart disease is unknown. Accordingly, this study aimed to establish the metabolic fate of NO and to determine the degree to which its levels are altered. Blood samples from 25 nonfasting patients with cyanotic congenital heart disease and 25 nonfasting normal controls were collected in Vacutainer tubes containing citrate dextrose and in separate Vacutainer tubes containing a solution that specifically preserves S-nitrosated Hb. Total NO species, plasma S-nitrosated proteins, iron nitrosyl Hb, and S-nitrosated Hb were quantified using chemiluminescence. In conclusion, a significant increase in plasma concentrations of NO metabolites and a modest increase in iron nitrosyl Hb levels were found, suggesting increased luminal consumption caused by erythrocytosis and further suggesting that hypoxemia might activate nonoxidative NO metabolic pathways and enhance tissue oxygen delivery.

Influence of intravenously administered leptin on nitric oxide production, renal hemodynamics and renal function in the rat

We investigated the effect of leptin on systemic nitric oxide (NO) production, arterial pressure, renal hemodynamics and renal excretory function in the rat. Leptin (1 mg/kg) was injected intravenously and mean arterial pressure (MAP), heart rate (HR), renal blood flow (RBF) and renal cortical blood flow (RCBF), were measured for 210 min after injection. Urine was collected for seven consecutive 30-min periods and blood samples were withdrawn at 15, 45, 75, 105, 135, 165 and 195 min after leptin administration. Leptin had no effect on MAP, HR, RBF, RCBF and creatinine clearance, but increased urine output by 37.8% (0–30 min), 32.4% (31–60 min) and 27.0% (61–90 min), as well as urinary sodium excretion by 175.8% (0–30 min), 136.4% (31–60 min) and 124.2% (61–90 min). In contrast, leptin had no effect on potassium and phosphate excretion. Plasma concentration of NO metabolites, nitrites+nitrates (NO x ), increased following leptin injection at 15, 45, 75 and 105 min by 27.7%, 178.1%, 156.4% and 58.7%, respectively. Leptin increased urinary NO x excretion by 241.6% (0–30 min), 552.6% (31–60 min), 430.7% (61–90 min) and 88.9% (91–120 min). This was accompanied by increase in plasma and urinary cyclic GMP. These data indicate that leptin stimulates systemic NO production but has no effect on arterial pressure and renal hemodynamics.

The role of nitric oxide in experimental cerulein induced pancreatitis.

An enhanced formation of nitric oxide (NO), due to the induction of inducible nitric oxide synthase (iNOS), has been implicated in the pathogenesis of shock and inflammation, but its role in acute pancreatitis still remains controversial. To clarify the role of NO in acute pancreatitis, the present experiment investigated the expression of iNOS and the effect of NOS inhibition on cerulein-induced pancreatitis in rats. Group I received intraperitoneal (ip) injection of normal saline. Group II received two ip injections of cerulein (20 microgram/kg). Group III received injections of N(G)-nitro-L-arginine methyl ester (L-NAME) (30 mg/kg) with cerulein. Group IV received L-arginine (250 mg/kg) with cerulein and L-NAME. The expression of iNOS in the pancreas was examined by western blot analysis. The plasma concentration of NO metabolites was measured. The severity of pancreatitis was assessed by measuring serum amylase, pancreas water content and histopathological examination. Compared with controls, the cerulein group displayed significantly increased expression of iNOS and raised plasma NO metabolites. Treatment with L-NAME significantly decreased hyperamylasemia, plasma NO level, and the extent of pancreatic injury. Treatment with L-arginine reversed the effects of L-NAME. These findings suggest that an enhanced formation of NO by iNOS plays an important role in the development of acute pancreatitis, and inhibition of NO production has the beneficial effects in reducing pancreas injury.

Human leptin stimulates systemic nitric oxide production in the rat.

Apart from having an effect on energy balance, leptin is also involved in cardiovascular regulation and in the pathogenesis of obesity-associated hypertension. We investigated the effect of leptin on nitric oxide (NO) production. Wistar rats were placed in metabolic cages, and urine was collected in 2-hour periods. After the control period, leptin (1 mg/kg intraperitoneal) was administered, and urine collection was continued for up to 6 hours. Blood was obtained 0.5, 1, 2, 4, and 6 hours after hormone injection. Leptin increased plasma concentrations of NO metabolites (nitrates + nitrites, NO(x)) by 32.5%, 58.0%, and 29.7% at 1, 2, and 4 hours, respectively. Urinary NO(x) excretion increased by 28.8% in the first and by 20.1% in the second 2-hour period after injection. The plasma concentration of the NO second messenger, cyclic guanosine 3',5'-monophosphate (cGMP), increased by 83% and 50.6% at 2 and 4 hours after leptin administration, respectively. Urinary excretion of cyclic GMP increased by 36.1% in the first and by 43.1% in the second 2-hour period. Leptin had no effect on the plasma concentration of atrial natriuretic peptide (ANP). The effect of leptin on plasma and urinary NO(x) was abolished by the NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME) (30 mg/kg intraperitoneal) administered 15 minutes before leptin injection. L-NAME alone caused a 32.2% increase in systolic blood pressure, but this increase was not observed in rats receiving L-NAME and leptin. The results indicate that leptin stimulates systemic NO production; leptin prevents blood pressure elevation induced by acute NO blockade, suggesting that leptin also triggers additional hypotensive mechanisms; and ANP is not involved in renal and vascular effects of leptin.

Cerebral Thrombosis And Microcirculation Of The Rat During The Oestrous Cycle And After Ovariectomy

1. The effects of oestrogen on thrombogenesis and the cerebral microcirculation of the female rat were studied during the oestrous cycle and after ovariectomy. 2. Serum levels of oestradiol (E2) and plasma concentrations of nitric oxide (NO) metabolites were significantly greater at pro-oestrus than at dioestrus. Blood vessel diameter, mean red cell velocity, wall shear rate and blood flow at pro-oestrus were significantly higher than at dioestrus. Thrombotic tendency, assessed using a He-Ne laser-induced thrombosis model, was significantly decreased at pro-oestrus compared with dioestrus. 3. The long-term deprivation of oestrogen by ovariectomy significantly depressed serum levels of E2 and plasma concentrations of NO metabolites. Thrombotic tendency was significantly increased 4 weeks after ovariectomy. Vessel diameter, mean red cell velocity, wall shear rate and blood flow in pial arterioles were significantly reduced after ovariectomy. 4. Exogenous administration of oestrogen (17 beta-oestradiol) after surgery reversed the increased thrombotic tendency mediated by ovariectomy. 5. These results strongly indicate that oestrogen mediates beneficial effects on the cerebral microcirculation and moderates cerebral thrombotic mechanisms in the female rat.

Two patterns of lipid deposition in the cholesterol-fed rabbit.

A central feature of arterial lipid deposition is its nonuniform and variable distribution. In immature human and rabbit aortas, spontaneous lesions occur most frequently downstream of branch points, but they tend to occur upstream of the same branches at later ages. In cholesterol-fed rabbits, the juvenile pattern has been seen regardless of age. These distributions may be determined by transport properties of the arterial wall, because uptake of plasma macromolecules is elevated downstream of aortic branches in immature rabbits and upstream in mature ones, except during cholesterol feeding, when the juvenile pattern is seen in adult vessels. The effect of cholesterol could reflect its inhibitory influence on the nitric oxide (NO) pathway because the adult transport pattern is NO dependent. Using protocols expected to preserve NO function and the mature pattern of transport during hypercholesterolemia, we made 2 attempts to induce upstream disease in rabbits. In trial I, plasma concentrations of cholesterol were kept within the normal human range for 15 weeks by using dietary levels of 0.05% to 0.2%. Although disease patterns reverse with age in human vessels exposed to these concentrations, lesions in both immature and mature rabbits occurred downstream of intercostal branch ostia. Trial II used older rabbits, a different base diet containing more vitamin E (96 mg/kg rather than 57 mg/kg), and higher levels of cholesterol (1%, administered for 8 weeks). For some animals, extra vitamin E (2000 mg/kg) was added to the diet. The mature pattern of lipid deposition was apparent around intercostal branches in the first group and was accentuated by the additional vitamin E, a change that was associated with a significant increase in the plasma concentration of NO metabolites. Spontaneous lesions, assessed on the base diet, were too rare to have influenced these distributions. This is the first report of upstream disease in the cholesterol-fed rabbit. The results support but do not prove the view that NO and transport are important in atherogenesis.

Circulating levels of nitric oxide in fertile women in relation to the menstrual cycle

To investigate nitric oxide (NO) production in the two phases of normal menstrual cycle. Prospective clinical study. Normal human volunteers in an academic research environment. Fifteen normally cycling women. Follicle growth monitoring by ultrasound, serum, and plasma sampling in the midfollicular phase, at ovulation, and in the midsecretory phase. Plasma concentration of NO stable oxidation products and serum concentrations of E2 and P. Plasma concentration of NO metabolites resulted higher in the follicular phase with respect to the secretory phase and peaked at midcycle. The results strongly support the existence of an E2 control of NO production and release. The significant reduction in NO metabolites observed in the secretory phase suggests a possible opposing action of P on either NO production or release.