SUMMARYWe have investigated whether differences seen in the pharmacological and morphological properties of mesenteric resistance vessels from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) controls are also present in vessels from young SHR and WKY rats in which there is little difference in blood pressure (BP). Segments of small arteries (lumen diameter 150 ^m) were taken from a specific location in the mesenteric bed of 6-, 12-, and 24-week-old SHR and WKY rats, and mounted on a myograph capable of directly measuring their tension. Vessels were set to internal circumference L, = 0.8 Lin,, where L l00 was an estimate of the internal circumference the vessels would have had when relaxed in situ and under a transmural pressure of 100 mm Hg. At all ages, compared with WKY vessels, the effective lumen diameter, I, = L,/x, was smaller in the SHR vessels. However, media hypertrophy was seen only in vessels from 12-and 24-week-old SHRs. In physiological salt solution the noradrenaline sensitivity of all vessels was similar (ED M * 2.4 nM). However, inhibition of neuronal uptake with cocaine revealed that at all ages the noradrenaline sensitivity of the vascular smooth muscle cells in the SHR vessels was greater than that of the cells in the WKY vessels. The results also suggested that the neuronal noradrenaline uptake was greater in the SHR vessels at all ages. The main increase in BP in the SHRs occurred between the ages of 6 week and 12 weeks. The results are therefore consistent with the hypothesis that differences in the structure of the resistance vessels are among the factors responsible for the development and maintenance of genetic hypertension. However, they point also to the possible involvement of differences in the noradrenaline sensitivity of the smooth muscle cells in the resistance vessel wails. 1 is associated with an increased peripheral resistance.' The increased resistance may be due to a decreased caliber in the resistance vessels 4 '' or to vessel rarification,"" 8 but, in any case, the factors that determine the caliber of the resistance vessels must play an important part. These factors include the morphological characteristics of Received July 16, 1979; revision accepted February 6, 1980. the vessels and the degree of their activation, which in part is controlled by the autonomic nervous system. The primary transmitter is noradrenaline, and the sensitivity of the vessels to this agonist together with their morphology are two factors of importance to our understanding of the etiology of hypertension in the SHR.We have shown' that, compared with vessels from Wistar-Kyoto rat (WKY) controls, third-branch mesenteric resistance vessels from 20-week-old SHRs have a smaller lumen, a thicker media, but the same in vitro noradrenaline sensitivity. Recently, however, Whall and colleagues, 10 using a preparation similar to ours, have demonstrated that destruction of the nervous supply in vitro by 6-hydroxy-dopamine 11 reveals that smooth muscle cell sensitivity to noradrenal...

C-reactive protein (CRP) is a sensitive marker for low-grade inflammation. Long-chain n-3 polyunsaturated fatty acids (PUFA) have anti-inflammatory effects. The objective of the present study was to investigate the effect on serum levels of CRP of n-3 PUFA at two different doses. We also investigated correlations between CRP and the cellular contents of PUFA. Sixty healthy volunteers (twenty-five women and thirty-five men) were randomly assigned to three treatment groups in a double-blind design. The subjects received a supplement of either 6·6 g n-3 PUFA/d, 2·0 g n-3 PUFA/d or placebo (olive oil) for 12 weeks. CRP was measured using a highly sensitive assay. The median serum CRP concentration was 0·78 mg/l. No significant correlations were found between CRP and the content of n-3 PUFA in granulocytes or platelets. Subjects receiving n-3 PUFA had a significant (P, 0·01) increase in the cellular contents of 20 : 5n-3, 22 : 5n-3 and 22 : 6n-3, with the largest increase occurring in the group receiving 6·6 g PUFA/d. A significant (P, 0·01) decrease in cellular content of 18 : 2n-6 and 20 : 4n-6 was observed simultaneously. Serum CRP concentrations, however, were unaffected by the PUFA-containing supplements. The present study shows that dietary supplementation with PUFA-containing supplements has no effect on serum concentrations of CRP, measured with a highly sensitive assay, in healthy subjects.

Background: Studies of long-term intake of industrially produced trans fatty acids (TFA) and n-3 polyunsaturated fatty acids (PUFA) suggest opposite effects on cardiovascular disease risk. Common mechanisms of action are probable. Objective: To examine the effects on cardiovascular risk markers of dietary enrichment with TFA or n-3 PUFA. Design: Randomized, double-blind, parallel intervention trial. Setting: Department of Human Nutrition, The Royal Veterinary and Agricultural University. Subjects: In all, 87 healthy males included, 79 completed. Intervention: Subjects were randomly assigned to 8 weeks of a daily intake of 33 g of experimental fats from either partially hydrogenated soy oil containing 20 g of TFA, 12 g of fish oil with approximately 4 g of n-3 PUFA and 21 g of control fat, or 33 g of control fat. The experimental fats were incorporated into bakery products. Plasma lipids, blood pressure, heart rate variability (HRV), arterial dilatory capacity, compliance, and distensibility were recorded before and after intervention and at follow-up 12 weeks after the intervention. Results: High-density lipoprotein cholesterol (HDL-C) decreased in the TFA group and triglycerides and mean arterial blood pressure decreased in the n-3 PUFA group compared to the control group. HRV, arterial dilatory capacity, compliance, and distensibility were unchanged. Conclusion:The results indicate that the association between coronary heart disease risk and intake of TFA and n-3 PUFA relates only modestly to changes in traditional risk markers.

BackgroundIron deficiency anaemia is common in patients with chronic kidney disease, and intravenous iron is the preferred treatment for those on haemodialysis. The aim of this trial was to compare the efficacy and safety of iron isomaltoside 1000 (Monofer®) with iron sucrose (Venofer®) in haemodialysis patients.MethodsThis was an open-label, randomized, multicentre, non-inferiority trial conducted in 351 haemodialysis subjects randomized 2 : 1 to either iron isomaltoside 1000 (Group A) or iron sucrose (Group B). Subjects in Group A were equally divided into A1 (500 mg single bolus injection) and A2 (500 mg split dose). Group B were also treated with 500 mg split dose. The primary end point was the proportion of subjects with haemoglobin (Hb) in the target range 9.5–12.5 g/dL at 6 weeks. Secondary outcome measures included haematology parameters and safety parameters.ResultsA total of 351 subjects were enrolled. Both treatments showed similar efficacy with >82% of subjects with Hb in the target range (non-inferiority, P = 0.01). Similar results were found when comparing subgroups A1 and A2 with Group B. No statistical significant change in Hb concentration was found between any of the groups. There was a significant increase in ferritin from baseline to Weeks 1, 2 and 4 in Group A compared with Group B (Weeks 1 and 2: P < 0.001; Week 4: P = 0.002). There was a significant higher increase in reticulocyte count in Group A compared with Group B at Week 1 (P < 0.001). The frequency, type and severity of adverse events were similar.ConclusionsIron isomaltoside 1000 and iron sucrose have comparative efficacy in maintaining Hb concentrations in haemodialysis subjects and both preparations were well tolerated with a similar short-term safety profile.

Background and objectives Several studies have reported beneficial cardiovascular effects of marine n-3 polyunsaturated fatty acids. To date, no large studies have investigated the potential benefits of marine n-3 polyunsaturated fatty acids in recipients of renal transplants.Design, setting, participants, & measurements In this observational cohort study of 1990 Norwegian recipients of renal transplants transplanted between 1999 and 2011, associations between marine n-3 polyunsaturated fatty acid levels and mortality were investigated by stratified analysis and multivariable Cox proportional hazard regression analysis adjusting for traditional and transplant-specific mortality risk factors. Marine n-3 polyunsaturated fatty acid levels in plasma phospholipids were measured by gas chromatography in a stable phase 10 weeks after transplantation.Results There were 406 deaths (20.4%) during a median follow-up period of 6.8 years. Mortality rates were lower in patients with high marine n-3 polyunsaturated fatty acid levels ($7.95 weight percentage) compared with low levels (,7.95 weight percentage) for all age categories (pooled mortality rate ratio estimate, 0.69; 95% confidence interval, 0.57 to 0.85). When divided into quartiles according to marine n-3 polyunsaturated fatty acid levels, patients in the upper quartile compared with the lower quartile had a 56% lower risk of death (adjusted hazard ratio, 0.44; 95% confidence interval, 0.26 to 0.75) using multivariable Cox proportional hazard regression analysis. There was a lower hazard ratio for death from cardiovascular disease with high levels of marine n-3 polyunsaturated fatty acid and a lower hazard ratio for death from infectious disease with high levels of the marine n-3 polyunsaturated fatty acid eicosapentaenoic acid, whereas there was no association between total or individual marine n-3 polyunsaturated fatty acid levels and cancer mortality.Conclusions Higher plasma phospholipid marine n-3 polyunsaturated fatty acid levels were independently associated with better patient survival.