Uric acid modulates vascular endothelial function through the down regulation of nitric oxide production

Abstract

Endothelial dysfunction characterized by decreased nitric oxide (NO) bioavailability is the first stage of coronary artery disease. It is known that one of the factors associated with an increased risk of coronary artery disease is a high plasma level of uric acid. However, causative associations between hyperuricaemia and cardiovascular risk have not been definitely proved. In this work, we tested the effect of uric acid on endothelial NO bioavailability. Electrochemical measurement of NO production in acetylcholine-stimulated human umbilical endothelial cells (HUVECs) revealed that uric acid markedly decreases NO release. This finding was confirmed by organ bath experiments on mouse aortic segments. Uric acid dose-dependently reduced endothelium-dependent vasorelaxation. To reveal the mechanism of decreasing NO bioavailability we tested the effect of uric acid on reactive oxygen species production by HUVECs, on arginase activity, and on acetylcholine-induced endothelial NO synthase phosphorylation. It was found that uric acid increases arginase activity and reduces endothelial NO synthase phosphorylation. Interestingly, uric acid significantly increased intracellular superoxide formation. In conclusion, uric acid decreases NO bioavailability by means of multiple mechanisms. This finding supports the idea of a causal association between hyperuricaemia and cardiovascular risk.     

Responses of wild plants to nitrate availability

Summary Two annual species of Bromus, an invader (B. hordeaceus, ex B. mollis) and a non-invader (B. intermedius), were grown for 28 days in growth chambers, at 5 and 100 M NO ₃ ^- in flowing nutrient solution. No differences between the two species were observed at either NO ₃ ^- level, in terms of relative growth rate (RGR) or its components, dry matter partitioning, specific NO ₃ ^- absorption rate, nitrogen concentration, and other characteristics of NO ₃ ^- uptake and photosynthesis. The effects of decreasing NO ₃ ^- concentration in the solution were mainly to decrease the NO ₃ ^- concentration in the plants through decreased absorption rate, and to decrease the leaf area ratio through increased specific leaf mass and decreased leaf mass ratio. Organic nitrogen concentration varied little between the two treatments, which may be the reason why photosynthetic rates were not altered. Consequently, RGR was only slightly decreased in the 5-M treatment compared to the 100-M treatment. This is in contrast with other species, where growth is reduced at much higher NO ₃ ^- concentrations. These discrepancies may be related to differences in RGR, since a log-linear relationship was found between RGR and the NO ₃ ^- concentration at which growth is first reduced. In addition, a strong linear relationship was found between the RGR of these species and their maximum absorption rate for nitrate, suggesting that the growth of species with low maximum RGR may be partly regulated by nutrient uptake.     

Disturbed lipid metabolism in diabetic coronary vessels

The aim of this study was to clarify whether or not arachidonic acid metabolic disorders are caused by a substrate inavailability and whether such disorders might contribute to circulatory disturbances in the diabetic myocardium. Norepinephrine induced a decrease in the conductivity of both coronary arterial bed and myocardial microcirculation in alloxan-diabetic dogs. It was markedly (p < 0.05) attenuated both by indomethacin and acetylsalicylic acid pretreatments indicating an imbalance among the vasoactive prostanoids in diabetes. TXA₂ release from the diabetic coronary rings was found to be elevated and could be normalized after the blockade of vascular adrenoceptors by phentolamine (p < 0.05). PGIZ synthesis was also enhanced by adrenergic blockade in the diabetic arterial rings. After pretreatment with ^l4C arachidonic acid, in order to measure substrate availability, the arachidonic acid metabolic rate was less in the diabetic coronary arteries than in healthy vessels (p < 0.05). Ten µmol/1 norepinephrine decreased arachidonic acid metabolism in the presence of prelabelled substrate in the diabetic animals, compared to an increase observed in metabolically healthy dogs. Therefore diabetes appears to diminish arachidonic acid metabolism and uptake independent of adrenoceptors and to induce an imbalance between vasoconstrictor and vasodilator cyclooxygenase products, resulting in elevated TXA₂ release controlled by adrenergic mechanisms which may contribute to an impairment in myocardial microcirculation.Abbreviations 6-oxo-PGF₁ 6-oxo prostaglandin F₁ - HPLC High Pressure Liquid Chromatograph - LAD Left Anterior Descending (coronary artery) - PGI₂ Prostacyclin - TXA₂ Thromboxane     

Distribution of the pulmonary artery and vein of the orangutan lung

The distribution of the pulmonary artery and vein of the orangutan lung was examined. The right pulmonary artery runs obliquely across the ventral side of the right bronchus at the caudally to the right upper lobe bronchiole. It then runs across the dorsal side of the right middle lobe bronchiole. Thereafter it runs obliquely across the dorsal side of the right bronchus, and then along the dorso-medial side of the right bronchus. This course is different from that in other mammals. During its course, it gives off branches which run mainly along the dorsal or lateral side of each bronchiole. The left pulmonary artery runs across the dorsal side of the left middle lobe bronchiole, then along the dorso-lateral side of the left bronchus, giving off branches which run along each bronchiole. The pulmonary veins run mainly the ventral or medial side of, along or between the bronchioles. In the left lung, the left middle lobe vein has two trunks; one enters the left atrium, and the other enters the left lower lobe pulmonary venous trunk. This is also different from that found in most mammals. Finally, the pulmonary veins enter the left atrium with four large veins.     

The bronchial tree,lobular division,and blood vessels of the lung of the silvered lutong (Presbytis cristata)

The lungs of three silvered lutongs (Presbytis cristata) were examined. The right and left lungs have the dorsal, lateral, ventral, and medial bronchiole systems, which arise from the corresponding sides of both bronchi, respectively. Bronchioles in the dorsal and lateral bronchiole systems are well developed, whereas those in the ventral and medial bronchiole systems are poorly developed and lack some portions. According to the fundamental structure of bronchial ramifications of the mammalian lung (Nakakuki, 1975, 1980), the right lung consists of the upper, middle, lower, and accessory lobes, whereas the left lung consists of a bilobed middle lobe and a lower lobe, in which the right upper lobe is extremely well developed. The right pulmonary artery runs across the ventral side of the right upper lobe bronchiole, and then across the dorsal side of the right middle lobe bronchiole. Initially it runs along the lateral side of the right bronchus and then gradually comes to run along the dorsal side. During its course, it gives off branches which run mainly along the dorsal or lateral side of the bronchiole. The left pulmonary artery runs across the dorsal side of the left middle lobe bronchiole, and then follows the same course as that in the right lower lobe. The pulmonary veins run medially or ventrally to the bronchioles, and finally enter the left atrium as four or five large veins.     

The effect of soil phosphorus on the external mycelium growth of arbuscular mycorrhizal fungi during the early stages of mycorrhiza formation

The effects of soil P amendments and time of application on the formation of external mycelium by different arbuscular mycorrhizal (AM) fungi were studied. In the first experiment the external mycelium produced in the soil by the AM fungus Glomus etunicatum Beck. and Gerd., during the early stages of root colonization (7 and 14 days after inoculation), was quantified by the soil-agar film technique. A Brazilian Oxisol was used with three different phosphate levels, varying from deficient to supra-optimal for the plant. Significant differences were observed in the phosphate and inoculation treatments for plant dry weight, P content in the tissue, root length and root colonization, at fourteen days after planting. At 7 days, mycelium growth, root colonization and their relationship were reduced at supra-optimal P concentrations. Applications of P one week after planting reduced mycelium growth and root colonization more than when applied to the soil before planting. In a second experiment the arbuscular mycorrhizal (AM) fungi, Scutellospora heterogama (Nicol. and Gerd.) Walker and Sanders and E3 were tested and compared with Glomus etunicatum. For the species studied, the length of external hyphae per unit of colonized root length was affected by small P additions but no further significant differences were observed at high P levels. The three AM endophytes showed marked differences in their response to P in the soil: Scutellospora heterogama, although producing external mycelium more profusely than the Glomus spp., showed a higher sensitivity to soil P supply.     

Simple electromyographic biofeedback treatment for chronic pediatric constipation/encopresis: Preliminary report

Pediatric constipation/encopresis is thought to be due, in part, to paradoxical constriction of the external anal sphincter (EAS) muscle during attempted defecation. This inappropriate contraction can lead to delayed, impacted, painful, and infrequent bowel movements. Standard Medical Care (SMC) involves disimpaction with enemas, followed by laxative therapy and diet modification, to maintain frequent soft stools. Using the case control method, the efficacy of SMC alone was compared with SMC plus EAS electromyographic biofeedback aimed at eliminating paradoxical contraction. Thirteen consecutive chronically constipated children received SMC plus biofeedback, and were compared with 13 age- and sex-matched children who received only SMC. Biofeedback subjects demonstrated post-treatment elimination of EAS paradoxical constriction. At 16 months follow-up parents of biofeedback children reported significantly greater improvement in constipation, encopresis, laxative use, and painful bowel movements compared to SMC.This research report was supported by the NIH under grant No. RO1 HD 28160.     

Matching models of left ventricle and systemic artery

To reveal how the matching models of the left ventricle and its afterload affect the pressure and flow in the aortic root, the differences between the measured pressure and flow waveforms and those determined by three kinds of matching model were compared. The results showed that, compared with the results by both matching models 1 and 2, the pressure and flow waveforms determined by matching model 3 established in this work were in the closest agreement with the corresponding experimental waveforms, therefore indicating that matching model 3 was a matching model that closely and rationally characterized the match between the left ventricle and the systemic artery.     

Filaments and rod-shaped tubulated bodies in the endothelia of anterior cerebral arteries in young rats

Summary Endothelia of the anterior cerebral arteries in rats aged 1 to 3 days were studied. Thin (about 50–90 Å) and thick (about 100–110 Å) filaments are present in the endothelia. Numerous spherical- or rod-shaped bodies, measuring approximately 0.07 to 0.3 m in diameter and up to 0.6 m in length occur in the endothelial cells. These bodies contain a tubular structure. The diameter of the individual tubules is about 200 Å. The present observations suggest that spherical- or rod-shaped inclusions are first synthesized in the rough endoplasmic reticulum and thereafter these materials are transported into the Golgi complex for maturation. A small number of the inclusions, however, may originate directly from the rough endoplasmic reticulum and not pass through the Golgi apparatus.A part of this study was demonstrated at the 70th Versammlung der Anatomischen Gesellschaft in Düsseldorf, April, 1–5, 1975The author thanks Mr. Tatsuro Fukushima for preparation of photographs