(2001) Variation in the helminth community structure in bank voles (Clethrionomys glareolus) from three comparable localities in the Mazury Lake District region of Poland. Parasitology, 123 (4 A note on versions:The version presented here may differ from the published version or from the version of record. If you wish to cite this item you are advised to consult the publisher's version. Please see the repository url above for details on accessing the published version and note that access may require a subscription. We tested the null hypothesis that populations of hosts trapped in isolated neighbouring locations showing comparable habitat quality, should support similar helminth parasite communities. The study was undertaken in a 2-week period in late summer in NE Poland in a single year, thereby eliminating seasonal and between-year variation in parasite burdens. A total of 139 Clethrionomys glareolus (bank vole) were sampled from 3 forest sites of similar habitat quality. Total species richness was 11 (6 nematodes and 5 cestodes) with 85n6 % of the voles carrying at least 1 species and an overall mean species richness of 1n4. At the component community level, the fewest species of helminths were recorded from site 2 (n l 6, compared with 9 at each of the other sites), but site 3 had the lowest Berger-Parker Dominance Index and the highest Simpson 's Index of Diversity. At the infracommunity level, site 3 had the highest mean no. of helminth species\vole, the highest mean Brillouin 's Index of Diversity but the lowest mean no. of helminths\vole. Voles from sites 1 and 3 differed in the nematodes that were most common (site 1, Heligmosomum mixtum -95 % ; site 3, Heligmosomoides glareoli -79n3 %). At site 2 no species exceeded 50 % but prevalence of Syphacia petrusewiczi was higher than at the other sites. The prevalence of cestodes was too low to test reliably (12n9 %), but the highest prevalence of adult cestodes was recorded at site 1 (22n5 % compared with 4n9 and 1n7 % for sites 2 and 3 respectively). Host sex did not influence infection, but mean species richness increased with age. The different sites were responsible for most of the variation in our data, and the intrinsic factors (sex and age) were less important in shaping the component community structure of helminths. We conclude that even locations in relative close proximity to one another (13-25 km), selected on the basis of similar habitat quality, have rodent populations that differ in their helminth parasite communities, although for reasons other than the factors quantified in the present study.

Obesity is a risk factor for stroke, but the mechanisms by which obesity increases stroke risk are unknown. Because microvascular architecture contributes to the outcome of stroke, we hypothesized that middle cerebral arteries (MCA) from obese Zucker rats (OZR) undergo inward remodeling and develop increased myogenic tone compared to lean Zucker rats (LZR). We further hypothesized that OZR have an increased infarct following cerebral ischemia and that changes in vascular structure and function correlate with the development of hypertension in OZR. Blood pressure was measured by telemetery in LZR and OZR from 6 to 17 weeks of age. Vessel structure and function were assessed in isolated MCAs. Stroke damage was assessed after ischemia was induced for 60 minutes followed by 24 hours of reperfusion. While mean arterial pressure (MAP) was similar between young rats (6-8 weeks old), MAP was higher in adult (14-17 weeks old) OZR than LZR. MCAs from OZR had a smaller lumen diameter and increased myogenic vasoconstriction compared to those from LZR. Following ischemia, infarction was 58% larger in OZR than LZR. Prior to the development of hypertension, MCA myogenic reactity and lumen diameter as well as infarct size were similar between young LZR and OZR. Our results indicate that the MCAs of OZR undergo structural remodeling and that these rats have greater cerebral injury following cerebral ischemia. These cerebrovascular changes correlate with the development of hypertension and suggest that the increased blood pressure may be the major determinant for stroke risk in obese individuals.

Jackson-Weaver O, Osmond JM, Riddle MA, Naik JS, Gonzalez Bosc LV, Walker BR, Kanagy NL. Hydrogen sulfide dilates rat mesenteric arteries by activating endothelial large-conductance Ca 2ϩ -activated K ϩ channels and smooth muscle Ca 2ϩ sparks. Am J Physiol Heart Circ Physiol 304: H1446 -H1454, 2013. First published March 22, 2013 doi:10.1152/ajpheart.00506.2012We have previously shown that hydrogen sulfide (H2S) reduces myogenic tone and causes relaxation of phenylephrine (PE)-constricted mesenteric arteries. This effect of H2S to cause vasodilation and vascular smooth muscle cell (VSMC) hyperpolarization was mediated by large-conductance Ca 2ϩ -activated potassium channels (BKCa). Ca 2ϩ sparks are ryanodine receptor (RyR)-mediated Ca 2ϩ -release events that activate BKCa channels in VSMCs to cause membrane hyperpolarization and vasodilation. We hypothesized that H2S activates Ca 2ϩ sparks in small mesenteric arteries. Ca 2ϩ sparks were measured using confocal microscopy in rat mesenteric arteries loaded with the Ca 2ϩ indicator fluo-4. VSMC membrane potential (Em) was measured in isolated arteries using sharp microelectrodes. In PE-constricted arteries, the H2S donor NaHS caused vasodilation that was inhibited by ryanodine (RyR blocker), abluminal or luminal iberiotoxin (IbTx, BKCa blocker), endothelial cell (EC) disruption, and sulfaphenazole [cytochrome P-450 2C (Cyp2C) inhibitor]. The H2S donor NaHS (10 mol/l) increased Ca 2ϩ sparks but only in the presence of intact EC and this was blocked by sulfaphenazole or luminal IbTx. Inhibiting cystathionine ␥-lyase (CSE)-derived H2S with ␤-cyano-L-alanine (BCA) also reduced VSMC Ca 2ϩ spark frequency in mesenteric arteries, as did EC disruption. However, excess CSE substrate homocysteine did not affect spark activity. NaHS hyperpolarized VSMC E m in PE-depolarized mesenteric arteries with intact EC and also hyperpolarized EC Em in arteries cut open to expose the lumen. This hyperpolarization was prevented by ryanodine, sulfaphenazole, and abluminal or luminal IbTx. BCA reduced IbTx-sensitive K ϩ currents in freshly dispersed mesenteric ECs. These results suggest that H2S increases Ca 2ϩ spark activity in mesenteric artery VSMC through activation of endothelial BKCa channels and Cyp2C, a novel vasodilatory pathway for this emerging signaling molecule.cytochrome P-450 epoxygenase; sodium hydrosulfide; membrane potential HYDROGEN SULFIDE (H 2 S) is a recently described vasodilator produced in the vasculature by the enzymes cystathionine ␥-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3MST). H 2 S has been proposed to cause vasodilation through a variety of mechanisms (1,3,26,33) and genetic knockout of the CSE gene causes hypertension (32). We previously reported that inhibiting CSE or disrupting the endothelium enhances myogenic tone in small mesenteric arteries from rats and that exogenous H 2 S hyperpolarizes vascular smooth muscle cell (VSMC) membrane potential (E m ) and dilates arteries through activation of large-conductance Ca 2ϩ -activated K (4) and ...

Objective-To determine if elasticity in blood vessels is compromised in circadian clock-mutant mice (Bmal1-knockout [KO] and Per-triple KO) and if matrix metalloproteinases (MMPs) might confer these changes in compliance. Methods and Results-High-resolution ultrasonography in vivo revealed impaired remodeling and increased pulse-wave velocity in the arteries of Bmal1-KO and Per-triple KO mice. In addition, compliance of remodeled arteries and naïve pressurized arterioles ex vivo from Bmal1-KO and Per-triple KO mice was reduced, consistent with stiffening of the vascular bed. The observed vascular stiffness was coincident with dysregulation of MMP-2 and MMP-9 in Bmal1-KO mice. Furthermore, inhibition of MMPs improved indexes of pathological remodeling in wild-type mice, but the effect was abolished in Bmal1-KO mice. Key Words: circadian rhythm Ⅲ extracellular matrix Ⅲ matrix Ⅲ metalloproteinases Ⅲ peripheral arterial disease Ⅲ prostaglandins Ⅲ vascular biology Ⅲ vascular stiffness T he cardiovascular system is governed and characterized by 24-hour rhythms. Recent observations have begun to establish that the genetic components that underlie circadian rhythm (the circadian clock) impart a significant influence in the regulation of the vascular system. Mice with a mutation of circadian clock components, including the integral component and transcription factor, Bmal1, exhibit acute vascular dysfunction 1,2 and aberrant chronic vascular responses in angiogenesis, 3 vascular remodeling, and injury. 1 The vascular defects in circadian-mutant mice may stem, at least in part, from impairments in endothelial function. [1][2][3][4] Indeed, endothelial mediators control the structural and mechanical properties of arteries by influencing smooth muscle cellularity and of extracellular matrix turnover to control elasticity and stiffness, 5,6 whose respective dysfunction is significantly correlated with the onset of vascular disease. 7 In the current study, we examine if elasticity in arteries and arterioles is compromised in Bmal1-knockout (KO) mice and if matrix metalloproteinases (MMPs) might confer these changes in compliance. Conclusion-Circadian Methods AnimalsAll experiments were conducted in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals and approved and monitored by the Medical College of Georgia, Augusta, Institutional Animal Care and Use Committee. Studies were conducted in 2 mouse models of circadian dysfunction having distinct mutations in the circadian clock; mice with disruption of the Bmal1 gene (Bmal1-KO) and disruption of all the Period gene isoforms (Period-1, Period-2, and Period-3/Per-triple KO [TKO]) and respective littermate control mice were used. Mice were housed under standard 12-hour light/dark conditions. Bmal1-KO and littermate wild-type (WT) mice were formerly produced by gene targeting in 129Sv/J embryonic stem cells, which we backcrossed 5 times to C57BL/6J. Animals were anesthetized by intraperitoneal injection of ketamine and xylazine. Ultra...

Hydrogen sulfide (HS) is a recently described gaseous vasodilator produced within the vasculature by the enzymes cystathionine γ-lyase and 3-mercaptopyruvate sulfurtransferase. Previous data demonstrate that endothelial cells (EC) are the source of endogenous HS production and are required for HS-induced dilation. However, the signal transduction pathway activated by HS within EC has not been elucidated. TRPV4 and large-conductance Ca-activated K channels (BK channels) are expressed in EC. HS-induced dilation is inhibited by luminal administration of iberiotoxin and disruption of the endothelium. Calcium influx through TRPV4 may activate these endothelial BK channels (eBK). We hypothesized that HS-mediated vasodilation involves activation of TRPV4 within the endothelium. In pressurized, phenylephrine-constricted mesenteric arteries, HS elicited a dose-dependent vasodilation blocked by inhibition of TRPV4 channels (GSK2193874A, 300 nM). HS (1 μM) increased TRPV4-dependent (1.8-fold) localized calcium events in EC of pressurized arteries loaded with fluo-4 and Oregon Green. In pressurized EC tubes, HS (1 μM) and the TRPV4 activator, GSK101679A (30 nM), increased calcium events 1.8- and 1.5-fold, respectively. HS-induced an iberiotoxin-sensitive outward current measured using whole cell patch-clamp techniques in freshly dispersed EC. HS increased K currents from 10 to 30 pA/pF at +150 mV. Treatment with NaS increased the level of sulfhydration of TRPV4 channels in aortic ECs. These results demonstrate that HS-mediated vasodilation involves activation of TRPV4-dependent Ca influx and BK channel activation within EC. Activation of TRPV4 channels appears to cause calcium events that result in the opening of eBK channels, endothelial hyperpolarization, and subsequent vasodilation.