Mechanism of the Vasodilator Action of Pinacidil

The mechanism of the vasodilator action of pinacidil has been studied in rat mesenteric small arteries. The results show, first, that the use of flux studies to make measurements of ion permeability requires knowledge of the membrane potential, especially as regards K+ permeability. Second, the results confirm that the vasodilator effect of pinacidil is due to an increase in K+ permeability. Lastly, the results suggest that the K+ channels involved are sensitive to glibenclamide

Micro-Water harvesting and soil amendment increase grain yields of barley on a Heavy-Textured alkaline sodic soil in a rainfed Mediterranean environment

This paper focuses on the adverse effects of soil sodicity and alkalinity on the growth of barley (Hordeum vulgare L.) in a rainfed environment in south-western Australia. These conditions cause the accumulation of salt (called ‘transient salinity’) in the root zone, which decreases the solute potential of the soil solution, particularly at the end of the growing season as the soil dries. We hypothesized that two approaches could help overcome this stress: (a) improved micro-water harvesting at the soil surface, which would help maintain soil hydration, decreasing the salinity of the soil solution, and (b) soil amelioration using small amounts of gypsum, elemental sulfur or gypsum plus elemental sulfur, which would ensure greater salt leaching. In our experiments, improved micro-water harvesting was achieved using a tillage technique consisting of exaggerated mounds between furrows and the covering of these mounds with plastic sheeting. The combination of the mounds and the application of a low rate of gypsum in the furrow (50 kg ha−1) increased yields of barley grain by 70% in 2019 and by 57% in 2020, relative to a control treatment with conventional tillage, no plastic sheeting and no amendment. These increases in yield were related to changes in ion concentrations in the soil and to changes in apparent electrical conductivity measured with the EM3

Eosinophils are key regulators of perivascular adipose tissue and vascular functionality

Obesity impairs the relaxant capacity of adipose tissue surrounding the vasculature (PVAT) and has been implicated in resultant obesity-related hypertension and impaired glucose intolerance. Resident immune cells are thought to regulate adipocyte activity. We investigated the role of eosinophils in mediating normal PVAT function. Healthy PVAT elicits an anti-contractile effect, which was lost in mice deficient in eosinophils, mimicking the obese phenotype, and was restored upon eosinophil reconstitution. Ex vivo studies demonstrated that the loss of PVAT function was due to reduced bioavailability of adiponectin and adipocyte-derived nitric oxide, which was restored after eosinophil reconstitution. Mechanistic studies demonstrated that adiponectin and nitric oxide are released after activation of adipocyte-expressed β3 adrenoceptors by catecholamines, and identified eosinophils as a novel source of these mediators. We conclude that adipose tissue eosinophils play a key role in the regulation of normal PVAT anti-contractile function

The contribution of previous lameness events and body condition score to the occurrence of lameness in dairy herds: a study of 2 herds

It has been demonstrated that low body condition and previous occurrence of lameness increase the risk of future lameness in dairy cows. To date the population attributable fraction (PAF), which provides an estimate of the contribution that a risk factor makes toward the total number of disease events in a population, has not been explored for lameness using longitudinal data with repeated measures. Estimation of PAF helps to identify control measures that could lead to the largest improvements on-farm. The aim of this study was to use longitudinal data to evaluate the proportion of lameness that could be avoided in 2 separate herds (2 populations) through (1) reduced recurrence of previous lameness events, (2) and moving body condition score (BCS) into more optimal ranges. Data were obtained from 2 UK dairy herds: herd A, a 200-cow herd with 8 yr of data from a total of 724 cows where lameness events were based on weekly locomotion scores (LS; 1 to 5 scale), and herd B, a 600-cow herd with data recorded over 44 mo from a total of 1,040 cows where treatment of clinical cases was used to identify lameness events. The PAF for categories of BCS were estimated using a closed equation appropriate for multiple exposure categories. Simulation models were used to explore theoretical scenarios to reflect changes in BCS and recurrence of previous lameness events in each herd. For herd A, 21.5% of the total risk periods (cow-weeks) contained a lameness event (LS 3, 4, or 5), 96% of which were repeat events and 19% were recorded with BCS 16 wk before a risk period. The median PAF estimated for changes in BCS were in the region of 4 to 11%, depending on severity of lameness. Repeated bouts of lameness made a very large contribution to the total number of lameness events. This could either be because certain cows are initially susceptible and remain susceptible, due to the increased risk associated with previous lameness events, or due to interactions with environmental factors. This area requires further research

Low body condition predisposes cattle to lameness: An 8-year study of one dairy herd

Lameness in dairy cows is a multifactorial and progressive disease with complex interactions between risk factors contributing to its occurrence. Detailed records were obtained from one United Kingdom dairy herd over an 8-yr period. Weekly locomotion scores were used to classify cows as not lame (score 1 to 2), mildly lame (score 3) and severely lame (score 4 to 5). These outcomes were used to investigate the hypothesis that low body condition score (BCS) is associated with an increased risk of lameness in dairy cows. Mixed effect multinomial logistic regression models were used to investigate the association between prior BCS and repeat lameness events during the longitudinal period of the study. Discrete time survival models were used to explore the relationship between prior BCS and first lifetime lameness events. In total, 79,565 cow weeks at risk were obtained for 724 cows. The number of lameness events was 17,114, of which 8,799 were categorized as mildly lame and 8,315 as severely lame. The median BCS was 2.25 (range, 0.75 to 4.25) and the mean body weight (BW) and age at first calving were 619.5 kg (range, 355.6 to 956.4 kg) and 25.8 mo (range, 20.5 to 37.8 mo), respectively. Subsets of the data were used in the discrete time survival models: 333 mild and 211 severe first lifetime lameness events in heifers (first lactation cows), and 81 mild and 49 severe first lifetime lameness events in cows second lactation or greater. Low BCS 3 wk before a repeated lameness event was associated with a significantly increased risk of lameness. Cows with BCS <2 were at greatest risk of mild or severe lameness, and an increased BCS above 2 was associated with a reduced risk of mild or severe lameness. Low BCS 16 or 8 wk before a first mild or severe lifetime lameness event, respectively, also had a positive association with risk of lameness in cows second lactation or greater. This provides evidence to support targeting management toward maintaining BCS to minimize the risk of lameness. Low BW (independent of BCS) and increased age at first calving above 24 mo were also associated with increased long-term risk of repeated lameness events. Overall, the model explained 62 and 60% of the variability for mild and severe lameness, respectively, highlighting the importance of these variables as risk factors and hence where management could be targeted to significantly affect reducing the risk of lameness

Lameness in dairy heifers; impacts of hoof lesions present around first calving on future lameness, milk yield and culling risk

The importance of lameness in primiparous dairy heifers is increasingly recognised. Although it is accepted that clinical lameness in any lactation increases the risk of future lameness, the impact of foot lesions during the first lactation on long-term lameness risk is less clear. This retrospective cohort study aimed to investigate the impacts of foot lesions occurring around the time of first calving in heifers on future lameness risk, daily milk yield and survival within a dairy herd. Records were obtained for 158 heifers from one UK dairy herd. Heifers were examined in 2 month blocks from 2 months pre-calving through to 4 months post-calving. Sole lesions and white line lesions were scored on a zero to 10 scale and digital dermatitis on a zero to 3 scale. Outcomes investigated were; lameness risk based on weekly locomotion scores, average daily milk yield and culling risk. Mixed effect models were used to investigate associations between maximum lesion scores and outcomes. Lesion scores in the highest score categories for claw horn lesions (sole lesions and white line lesions) in the 2 to 4 month post-calving period were associated with an increased risk of future lameness; heifers with white line lesion scores ≥3 compared with scores zero to 1 and heifers with sole lesion scores ≥4 compared with score 2, at this time point, had a predicted increased risk of future lameness of 1.6 and 2.6 respectively. Sole lesions ≥4 were also associated with a reduction in average daily milk yield of 2.68 kg. Managing heifers to reduce claw horn lesions during this time period post-calving may provide health, welfare and production benefits for the long-term future of those animals. A novel finding from the study was that mild lesion scores compared with scores zero to 1, were associated with a reduced risk of future lameness for white line lesions and sole lesions occurring in the pre-calving or 2 to 4 months post-calving periods respectively. Mild sole lesions in the pre-calving period were also associated with a reduced risk of premature culling. One hypothesis for this result is that a mild insult may result in adaptive changes to the foot leading to greater biomechanical resilience and so increased longevity

Intravenous leiomyomatosis of the uterus with extension to the right heart

A 42-year-old woman admitted with debilitation and engorgement both lower extremities. Transthoracic two-dimensional echocardiography, abdominal ultrasound and computerized tomography revealed a lobulated pelvic mass, a mass within right internal iliac vein, both common iliac vein, as well as the inferior vena cava, extending into the right atrium. In addition, echocardiography and abdominal ultrasound showed the tumor of right atrium and inferior vena cave has no stalk and has well-demarcated borders with the wall of right atrium and inferior vena cave. Hence, the presumptive diagnosis of IVL was made by echocardiography and abdominal ultrasound and the presumptive diagnosis of sarcoma with invasion in right internal iliac vein, both common iliac vein, the inferior vena cava, as well as the right atrium was made by multi-detector-row computerized tomography. The patient underwent a one-stage combined multidisciplinary thoraco-abdominal operation under general anaesthetic. Subsequently the pathologic report confirmed IVL

Raised tone reveals ATP as a sympathetic neurotransmitter in the porcine mesenteric arterial bed

The relative importance of ATP as a functional sympathetic neurotransmitter in blood vessels has been shown to be increased when the level of preexisting vascular tone or pressure is increased, in studies carried out in rat mesenteric arteries. The aim of the present study was to determine whether tone influences the involvement of ATP as a sympathetic cotransmitter with noradrenaline in another species. We used the porcine perfused mesenteric arterial bed and porcine mesenteric large, medium and small arteries mounted for isometric tension recording, because purinergic cotransmission can vary depending on the size of the blood vessel. In the perfused mesenteric bed at basal tone, sympathetic neurogenic vasocontractile responses were abolished by prazosin, an α1- adrenoceptor antagonist, but there was no significant effect of α,β-methylene ATP, a P2X receptor-desensitizing agent. Submaximal precontraction of the mesenteric arterial bed with U46619, a thromboxane A2 mimetic, augmented the sympathetic neurogenic vasocontractile responses; under these conditions, both α,β-methylene ATP and prazosin attenuated the neurogenic responses. In the mesenteric large, medium and small arteries, prazosin attenuated the sympathetic neurogenic contractile responses under conditions of both basal and U46619-raised tone. α,β-Methylene ATP was effective in all of these arteries only under conditions of U46619- induced tone, causing a similar inhibition in all arteries, but had no significant effect on sympathetic neurogenic contractions at basal tone. These data show thatATP is a cotransmitter with noradrenaline in porcine mesenteric arteries; the purinergic component was revealed under conditions of partial precontraction, which is more relevant to physiological conditions

Loss of anti-contractile effect of perivascular adipose tissue in offspring of obese rats

RATIONALE: Maternal obesity pre-programmes offspring to develop obesity and associated cardiovascular disease. Perivascular adipose tissue (PVAT) exerts an anti-contractile effect on the vasculature, which is reduced in hypertension and obesity. OBJECTIVE: The objective of this study was to determine whether maternal obesity pre-programmes offspring to develop PVAT dysfunction in later life. METHODS: Female Sprague–Dawley rats were fed a diet containing 10% (control) or 45% fat (high fat diet, HFD) for 12 weeks prior to mating and during pregnancy and lactation. Male offspring were killed at 12 or 24 weeks of age and tension in PVAT-intact or -denuded mesenteric artery segments was measured isometrically. Concentration–response curves were constructed to U46619 and norepinephrine. RESULTS: Only 24-week-old HFD offspring were hypertensive (P<0.0001), although the anti-contractile effect of PVAT was lost in vessels from HFD offspring of each age. Inhibition of nitric oxide (NO) synthase with 100 μM l-NMMA attenuated the anti-contractile effect of PVAT and increased contractility of PVAT-denuded arteries (P<0.05, P<0.0001). The increase in contraction was smaller in PVAT-intact than PVAT-denuded vessels from 12-week-old HFD offspring, suggesting decreased PVAT-derived NO and release of a contractile factor (P<0.07). An additional, NO-independent effect of PVAT was evident only in norepinephrine-contracted vessels. Activation of AMP-activated kinase (with 10 μM A769662) was anti-contractile in PVAT-denuded (P<0.0001) and -intact (P<0.01) vessels and was due solely to NO in controls; the AMPK effect was similar in HFD offspring vessels (P<0.001 and P<0.01, respectively) but was partially NO-independent. CONCLUSIONS: The diminished anti-contractile effects of PVAT in offspring of HFD dams are primarily due to release of a PVAT-derived contractile factor and reduced NO bioavailability

Maternal hyperleptinemia is associated with male offspring’s altered vascular function and structure in mice

Children of mothers with gestational diabetes have greater risk of developing hypertension but little is known about the mechanisms by which this occurs. The objective of this study was to test the hypothesis that high maternal concentrations of leptin during pregnancy, which are present in mothers with gestational diabetes and/or obesity, alter blood pressure, vascular structure and vascular function in offspring. Wildtype (WT) offspring of hyperleptinemic, normoglycemic, Lepr db/+ dams were compared to genotype matched offspring of WT-control dams. Vascular function was assessed in male offspring at 6, and at 31 weeks of age after half the offspring had been fed a high fat, high sucrose diet (HFD) for 6 weeks. Blood pressure was increased by HFD but not affected by maternal hyperleptinemia. On a standard diet, offspring of hyperleptinemic dams had outwardly remodeled mesenteric arteries and an enhanced vasodilatory response to insulin. In offspring of WT but not Leprdb/+ dams, HFD induced vessel hypertrophy and enhanced vasodilatory responses to acetylcholine, while HFD reduced insulin responsiveness in offspring of hyperleptinemic dams. Offspring of hyperleptinemic dams had stiffer arteries regardless of diet. Therefore, while maternal hyperleptinemia was largely beneficial to offspring vascular health under astandard diet, it had detrimental effects in offspring fed HFD. These results suggest that circulating maternal leptin concentrations may interact with other factors in the pre- and post-natal environments to contribute to altered vascular function in offspring of diabetic pregnancie