1,720,999 research outputs found
Increased efficacy of dietary supplement containing wax ester-rich marine oil and xanthophylls in a mouse model of dry macular degeneration
Full text linkAge-related macular degeneration (AMD) is nowadays considered among the retinal diseases whose clinical management lacks established treatment approaches, mainly for its atrophic (dry) form. In this respect, the use of dietary patterns enriched in omega-3 and antioxidant xanthophylls has emerged as a promising approach to counteract dry AMD progression although the prophylactic potential of omega-3 of fish origin has been discussed. Whether enriched availability of omega-3 and xanthophylls may increase the effectiveness of diet supplementation in preventing dry AMD remains to be fully established. The present study aims at comparing the efficacy of an existing orally administered formulation based on lutein and fish oil, as a source of omega-3, with a novel formulation providing the combination of lutein and astaxanthin with Calanus oil (COil), which contains omega-3 together with their precursors policosanols. Using a mouse model of dry AMD based on subretinal injection of polyethylene glycol (PEG)-400, we assessed the comparative efficacy of both formulations on PEG-induced major hallmarks including oxidative stress, inflammation, glial reactivity and outer retinal thickness. Dietary supplementation with both mixtures has been found to exert a significant antioxidant and anti-inflammatory activity as reflected by the overall amelioration of the PEG-induced pathological hallmarks. Noteworthy, the formulation based on COil appeared to be more protective than the one based on fish oil, presumably because of the higher bioavailability of omega-3 in COil. These results support the use of dietary supplements combining omega-3 and xanthophylls in the prevention and treatment of AMD and suggest that the source of omega-3 might contribute to treatment efficacy
Pial microvascular responses induced by transient bilateral common carotid artery occlusion in zucker rats.
No full textThis study was aimed to assess the in vivo geometric and functional characteristics of lean Zucker (ZL) and obese Zucker rat (ZO) pial microvascular networks and to evaluate the vascular responses to cerebral hypoperfusion-reperfusion. Rat pial microcirculation was observed by fluorescence microscopy through a closed cranial window. Bilateral common carotid artery occlusion (BCCAO) lasted 30 min and reperfusion 60 min. Arterioles were classified according to Strahler's ordering scheme. Arteriolar diameter was determined by computer assisted-method as well as permeability increase, leukocyte adhesion and perfused capillary length. Neuronal damage was evaluated by TTC staining. ZO rats did not show order 5 vessels; ZO pial arterioles showed high asymmetry in the largest vessels and reduced number of branchings compared with those detected in ZL and Wistar rats. BCCAO and reperfusion caused more severe microvascular damages in ZO compared with ZL and Wistar rats. Vascular responses to acetylcholine and papaverine in ZO rats were significantly reduced compared with Wistar and ZL rats under baseline condition and at the end of reperfusion. Moreover, ZO rats showed more pronounced lesion in the cortex and striatum. Obesity and hyperglycemia could increase vascular remodeling in cerebral networks, with elevated risk of adverse outcome after brain hypoperfusion-reperfusion
Evidence in hypertensive rats of hypotensive effect after mandibular extension
Full text linkPrevious studies in anesthetized normotensive rats demonstrated that a single mouth opening for 10 min obtained by an ad hoc dilator (mandibular extension [ME]) produced a blood pressure reduction by about 20 mmHg lasting for about 2 h and that once-repeated ME prolonged this effect. We here describe these effects in hypertensive rats. Mean (intra) arterial blood pressure (MABP) and heart rate (HR) was followed for up to a maximum of 470 min after single or repeated 10 min-lasting ME in two groups of anesthetized, male, 6-9 months old hypertensive rats. In one group, hypertension was induced by dexamethasone (20 μg/kg/day, subcutaneously for 7 days; Dex-HT); the other group was spontaneously hypertensive rats (SHR). Studies were done, in Dex-HT rats, after only surgical procedures (no ME, sham-operated rats), single ME, early repeated (after 10 min) ME (ER-ME) and late repeated (after 160 min) ME (LR-ME) and, in SHR, after only surgical procedures and ER-ME. One-way ANOVA for repeated measures revealed no significant effect on MABP and HR in sham-operated groups. In Dex-HT rats, single ME was followed by a significant MABP decline by 25 mmHg, lasting for 100 min; ER-ME and LR-ME were followed by an even greater significant MABP decline by 40 mmHg, which outlasted the experimental observation period. In SHR, ER-ME gave similar results as in Dex-HT rats. HR significantly declined in all, except sham-operated groups. In conclusions, ME is followed by a prolonged MABP decline also in hypertensive rats. This effect is even more pronounced, in length and magnitude, after repeated ME
Microvascular responses to aldosterone in hamster cheek pouch microcirculation
Full text linkThe aim of the present study was to assess the in vivo effects of aldosterone topically applied on the hamster cheek pouch microcirculation under baseline conditions or during ischemia-reperfusion. Male Syrian hamsters were anesthetized, tracheotomized and intubated. They were studied under baseline conditions or submitted to ischemia-reperfusion. Cheek pouch microvessels were visualized by fluorescence microscopy. Microvascular parameters were determined by computerized methods. Under baseline conditions, aldosterone (0.2, 0.5, 2.4 μM/L/2 min) induced dose-dependent constriction of all arterioles within 2.0 ± 0.5 min of administration. Diameter reduction was in the same range in smaller arterioles: A3 ones constricted by 24 ± 3% of baseline (at the highest dose). Aldosterone applied prior to ischemia and at reperfusion caused arteriolar constriction, marked microvascular permeability (0.66 ± 0.03 Normalized Grey Level), reduction in perfused capillary (-70 ± 4% of baseline) and leukocyte adhesion. All changes were statistically significant compared with ischemic animals. Potassium canrenoate (mineralcorticoid receptor inhibitor) prior to aldosterone did not abolish the aldosterone-induced effects, while valsartan (angiotensin II AT1 receptor inhibitor) prior to aldosterone ameliorated microvascular ischemia-reperfusion injury. In conclusion, aldosterone determined dose-dependent arteriolar constriction likely by angiotensin II type-1 receptor activation (non-genomic mechanism) worsening the effects of ischemia-reperfusion on capillary perfusion, while protecting from free radical formation
Novel Insights into Beta 2 Adrenergic Receptor Function in the rd10 Model of Retinitis Pigmentosa
Full text linkBackground: In retinitis pigmentosa (RP), inherited rod death is followed by cone loss and blindness. Why cones die is still a matter of consideration. Here, we investigate the pathogenic role of the sympathetic transmission in the rd10 mouse model of RP. Methods: Retinal levels of beta adrenergic receptor (BAR) 2 and norepinephrine (NE) were measured. After administration of the BAR1/2 blocker propranolol or the hypoxia-inducible factor (HIF)-1 activator dimethyloxalylglycine (DMOG), retinal levels of HIF-1α, BAR2 or proteins involved in BAR2 desensitization were also measured. In DMOG treated mice, expression and localization of BAR2, inflammatory markers and cone arrestin were determined. Finally, rd10 mice were subjected to electroretinogram (ERG) analysis to assess rod and cone function. Results: In the rd10 retina, BAR2 overexpression and NE accumulation were found, with BAR2 immunoreactivity localized to Müller cells. BAR2 overexpression was likely due to desensitization defects. Upregulated levels of BAR2 were drastically reduced by propranolol that also restored desensitization defects. Due to the low level of HIF-1 consequent to the hyperoxic environment in the rd10 retina, we hypothesized a link between HIF-1 and BAR2. HIF-1α stabilization with DMOG resulted in i. increased HIF-1α accumulation, ii. decreased BAR2 levels, iii. restored desensitization processes, iv. reduced expression of inflammatory markers and v. increased cone survival without improved retinal function. Conclusions: Our results support a pathogenic role of the sympathetic system in RP that might help to understand why rd10 mice show a positive response to BAR blockers
Effects of oleuropein and pinoresinol on microvascular damage induced by hypoperfusion and reperfusion in rat pial circulation
No full textObjective: The present study was aimed to assess the in vivo acute effects of oleuropein or/and pinoresinol, polyphenols widely diffused in natural sources, on rat pial microvascular responses during transient BCCAO and reperfusion.
Methods: Rat pial microcirculation was visualized by fluorescence microscopy through a closed cranial window. Pial arterioles were classified into five orders of branching. Capillaries were assigned order 0, the smallest arterioles order 1 and the largest ones order 5.
Results: Rats subjected to BCCAO and reperfusion showed: arteriolar diameter decrease, microvascular leakage, leukocyte adhesion in venules, and reduction in capillary perfusion. Pretreatment with oleuropein or pinoresinol, a higher dose before BCCAO determined dilation in all arteriolar orders RE. Microvascular leakage was reduced as well as leukocyte adhesion and ROS formation, while capillary perfusion was protected. Inhibition of endothelium nitric oxide synthase prior to oleuropein or pinoresinol reduced the effect of these polyphenols on pial arteriolar diameter and leakage. These substances, administered together, prevented microvascular damage to a larger extent.
Conclusion: Oleuropein and pinoresinol were both able to protect pial microcirculation from I-reperfusion injury, to increase nitric oxide release and to reduce oxidative stress preserving pial blood flow distribution
Repeated mandibular extension in rat: A procedure to modulate the cerebral arteriolar tone
Full text linkPrevious data have shown both in the rat and in the human that a single mandibular extension lasting 10 min induces a significant important and prolonged reduction in blood pressure and heart rate, affecting also rat pial microcirculation by the release of endothelial factors. In the present work, we assessed whether repeated mandibular extension could further prolong these effects. We performed two mandibular extensions, the second mandibular extension being applied 10 min after the first one. The second mandibular extension produced a reduction in blood pressure and heart rate for at least 240 min. As in the case of a single mandibular extension, pial arterioles dilated persisting up to 140 min after the second extension. Spectral analysis on 30 min recordings under baseline conditions and after repetitive mandibular extensions showed that the pial arterioles dilation was associated with rhythmic diameter changes sustained by an increase in the frequency components related to endothelial, neurogenic, and myogenic activity while a single mandibular extension caused, conversely, an increase only in the endothelial activity. In conclusion, repetitive mandibular extension prolonged the effects of a single mandibular extension on blood pressure, heart rate and vasodilation and induced a modulation of different frequency components responsible of the pial arteriolar tone, in particular increasing the endothelial activity
Evidence in the human of a hypotensive and a bradycardic effect after mouth opening maintained for 10 min
No full textPurpose: We have recently shown that in humans submaximal mouth opening associated with partial masticatory movements for 10 min is followed by a small but significant and prolonged reduction of blood pressure and heart rate. We here report the effects of a fixed mouth opener. Methods: In 22 seated normotensive volunteers the effect on blood pressure and heart rate was studied in randomized order after fixed mandibular extension and after a control procedure consisting in keeping a stick between the incisor teeth (both for 10 min). Automated recordings every 10 min were done for 40 min before and 120 min following the procedure. Results: Two-way ANOVA for repeated measures on absolute values (actual recordings) and on changes from baseline revealed that, compared to controls, systolic, diastolic and mean blood pressure and heart rate were significantly lower after mandibular extension. Compared to controls, mandibular extension induced an average blood pressure drop of 2.88 mmHg (systolic), 2.55 mmHg (diastolic) and 2.42 mmHg (mean) over the entire observation period. The average decline over the central part of the observation period (30th to 80th min) was, respectively, of 3.62, 3.70 and 3.61 mmHg. The decrements of heart rate were of 2.11 and 2.66 beats per min. All these differences were statistically significant. The hypotensive and bradycardic responses persisted for 70–120 min. Conclusions: This study shows that, in normotensives, a single fixed submaximal mouth opening for 10 min is followed by prolonged albeit small reductions of blood pressure and heart rate
Effetti della stimolazione del nervo trigemino sui parametri cardiovascolari e sul microcircolo piale in ratti ipertesi
No full textRIASSUNTO
Numerosi studi hanno dimostrato che la stimolazione a livello orofacciale del nervo trigemino, il più grande dei nervi cranici, induce nell’uomo una serie di riflessi, definiti riflessi trigemino-cardiaci, che influenzano i parametri cardiovascolari (Schaller et al., 1999).
Un recente studio condotto su soggetti volontari normotesi ha mostrato che una breve (10 min) apertura sub-massimale della bocca (EM) causava una prolungata e significativa riduzione della pressione arteriosa (PA) e della frequenza cardiaca (FC) (Brunelli et al., 2012). Gli autori hanno attribuito questi effetti alla stimolazione delle branche periferiche del nervo trigemino.
Studi condotti nel ratto normoteso hanno dimostrato che EM ottenuta con un apposito divaricatore posto tra le arcate dentarie, oltre ad indurre riduzione della pressione arteriosa media (PAM) e di FC, produceva effetti anche sull’emodinamica cerebrale. E’ stato visto infatti che durante EM si verificava una notevole riduzione del diametro delle arteriole piali seguita da una significativa vasodilatazione che perdurava per l’intero periodo di osservazione (Lapi et al., 2013). Tutti questi effetti erano aboliti dalla dissezione del nervo trigemino. Inoltre, attraverso tecniche di biologia molecolare e di analisi spettrale delle variazioni ritmiche del diametro arteriolare, è stato dimostrato che EM induceva, a livello del microcircolo piale, un maggior rilascio di NO endoteliale rispetto alle condizioni basali.
Pertanto, la stimolazione del nervo trigemino sembra innescare specifici meccanismi che regolano sia i parametri cardiovascolari sia il microcircolo piale. Nel presente lavoro di tesi sono state valutate in vivo le variazioni di PAM, FC e dell’emodinamica del microcircolo piale prima, durante e dopo EM singola e ripetuta in ratti resi ipertesi sperimentalmente e, in un particolare protocollo di doppia EM, anche in ratti normotesi. La rilevazione di PAM e di FC è stata effettuata rispettivamente mediante un apposito trasduttore collegato ad un catetere posto in arteria femorale, e registrazione di ECG, usando un apposito software. Mediante microscopia in fluorescenza sono state visualizzate le arteriole piali a livello della corteccia parietale, dove proiettano la maggior parte delle afferenze trigeminali, per poi misurarne i diametri off-line. Ciò ha consentito di classificare per la prima volta le arteriole del microcircolo piale di ratti ipertesi in base allo schema di Strahler, e valutare gli effetti di EM sul calibro delle arteriole.
Inoltre, sono state analizzate le ritmiche oscillazioni del diametro delle arteriole di ordine 2 tramite analisi spettrale su acquisizioni di almeno 30 minuti nel periodo di osservazione basale e a circa metà del periodo post EM.
Per ottenere una descrizione comparativa del microcircolo piale dei ratti normotesi e ipertesi, sono state condotte acquisizioni al microscopio a fluorescenza in condizioni basali delle arteriole piali dei 5 ratti normotesi e dei 18 ratti ipertesi utilizzati. Le arteriole sono state classificate in base al diametro, considerando la lunghezza e il numero delle ramificazioni, secondo lo schema centripeto di Strahler. Nei ratti ipertesi il network arteriolare piale ha mostrato diametri maggiori nelle arteriole di ordine superiore. Sia negli animali normotesi sia negli ipertesi, le arteriole di ordine 2 sono risultate le più numerose e anche per questo sono state prese in considerazione nel nostro studio.
Nella prima parte del lavoro, ratti ipertesi sono stati sottoposti, dopo 30 minuti di osservazione basale, ad una singola EM della durata di 10 minuti e, dopo rimozione del divaricatore i parametri considerati sono stati rilevati per ulteriori 160 minuti. Durante EM, PAM e FC non hanno subito variazioni significative rispetto ai valori basali, mentre le arteriole piali si sono costrette. Invece, nel periodo post EM, PAM si è ridotta significativamente a partire da 20 minuti e fino a 100 minuti per poi recuperare il valore basale a 160 minuti; FC è diminuita più tardi, a 60 minuti post EM, senza recuperare il valore iniziale per tutto il periodo di osservazione. Il diametro delle arteriole è aumentato progressivamente, mantenendosi dilatato fino a 160 minuti.
L’analisi spettrale delle sei componenti di oscillazione che caratterizzavano le variazioni dei diametri delle arteriole ha evidenziato che nei ratti ipertesi vi era un significativo aumento delle componenti a bassa frequenza relative all’attività endoteliale, miogena e un marcato aumento della componente neurogena rispetto alle condizioni basali.
Al fine di prolungare nel tempo gli effetti indotti da una singola EM, sono stati condotti esperimenti nei quali, in ratti ipertesi, ad una prima EM (EM1) sono seguiti un periodo di 160 minuti per il recupero di PAM, uno di 10 minuti di osservazione (basale 2), e quindi l’applicazione di una seconda EM (EM2) per 10 minuti ed infine un periodo post EM2 della durata di 240 minuti. EM2 ha prodotto un ulteriore abbassamento di PAM che si è mantenuto per tutto il periodo di osservazione post EM2 e un’ulteriore significativa dilatazione delle arteriole piali. Invece, FC non si è ridotta ulteriormente, oscillando per tutti i 240 minuti di osservazione intorno ai valori raggiunti nel post EM1. L’analisi spettrale delle sei componenti che caratterizzavano le variazioni del diametro arteriolare ha evidenziato che nei ratti ipertesi EM2 prolungava l’effetto indotto da EM1.
Al fine di ottenere le stesse risposte cardiovascolari a lungo termine riducendo il tempo che intercorre tra una EM e la successiva, è stato sperimentato un ulteriore protocollo che prevedeva una seconda apertura della bocca (EM2) dopo soli 10 minuti dalla prima. Questa metodica è stata applicata, dapprima, in ratti normotesi e successivamente in ratti ipertesi. Nei primi, EM2 non ha causato un’ulteriore riduzione di PAM rispetto ad EM1, ma ha determinato un’ulteriore significativa riduzione di FC e vasodilatazione rispetto ad EM1. Nei ratti ipertesi PAM ha subito un ulteriore decremento significativo dopo EM2 rispetto ad EM1, mentre FC non ha subito variazioni né dopo EM1 né dopo EM2. A livello cerebrale, una seconda EM ravvicinata alla prima ha indotto anche nei ratti ipertesi un’ulteriore significativa dilatazione delle arteriole piali rispetto ad EM1, che perdurava per l’intero periodo di osservazione. L’analisi spettrale delle ritmiche variazioni del diametro delle arteriole di ordine 2 ha evidenziato che una seconda EM applicata a soli 10 minuti dalla prima causava, sia nei ratti normotesi che negli ipertesi, un pronunciato incremento delle componenti correlate all’attività endoteliale (ULF e VLF1), neurogena (VLF2) e miogena (LF), rispetto alle condizioni basali. Nei ratti ipertesi l’aumento relativo all’attività endoteliale e neurogena è più spiccato rispetto a quello evidenziato nei ratti normotesi.
Ratti ipertesi sottoposti alla sola procedura chirurgica, non hanno mostrato variazione dei parametri considerati per tutto il periodo di osservazione che è stato di 480 minuti.
I risultati ottenuti indicano che una semplice manovra non invasiva, come EM, è in grado di ridurre i parametri cardiovascolari e di incrementare la perfusione cerebrale a lungo termine. Pertanto, potrebbe rappresentare un valido sostegno alla terapia farmacologica dell’ipertensione, patologia oggi molto diffusa e in continuo aumento nei paesi industrializzati
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