Alterations In Vascular Reactivity Research Articles

Esculetin attenuates alterations in Ang II and acetylcholine mediated vascular reactivity associated with hyperinsulinemia and hyperglycemia

Esculetin (6, 7- dihydroxycoumarin) was found to be protective against hepatic and renal damage associated with Streptozotocin (STZ) induced type 1 diabetes, because of its radical scavenging property. However, there are no reports regarding its effect on vascular dysfunction under hyperinsulinemic and hyperglycemic conditions. Hence, the present study aimed to investigate the effect of esculetin on vascular dysfunction under these conditions. Non-genetic model of hyperinsulinemia and hyperglycemia were developed by high fat diet (HFD) feeding and HFD + Streptozotocin (STZ, 35 mg/kg, I.P) treatment in Wistar rats, respectively. Esculetin was administered at 50 and 100 mg/kg/day (P.O, 2 weeks) doses and biochemical, vascular reactivity and immunohistochemical experiments were performed to assess the effect of esculetin on vascular dysfunctions. Esculetin treatment significantly attenuates metabolic perturbations, alleviates insulin levels in hyperinsulinemic condition. Thoracic aorta of hyperinsulinemic and hyperglycemic rats showed hyper-responsiveness to Ang II mediated contraction and impaired acetylcholine mediated relaxation, and esculetin attenuates alterations in vascular reactivity to Ang II and acetylcholine challenges. In addition, immunohistochemical evaluations revealed that esculetin prevents increase in AT1R, AT2R, Keap1, TGF-β, and decrease in ACE2 expression in aorta of hyperinsulinemic and hyperglycemic rats.

Expression and activity of matrix metalloprotease-2 in canine early placenta

Expression and activity of matrix metalloprotease-2 in canine early placenta

Wire Myography to Study Vascular Tone and Vascular Structure of Isolated Mouse Arteries.

Atherosclerosis is characterized by endothelial dysfunction and alterations in vascular reactivity, which can be investigated by wire myography. The method allows ex vivo monitoring of the transversal isometric tension developed by a vessel segment in response to different pathophysiological stimuli. Here we describe in detail how to use the wire myograph to evaluate endothelial function and vasoconstrictor or vasodilator properties of the vessel, as well as to identify and characterize different factors and molecular pathways that control vascular tone. We also describe how to use the wire myograph to analyze biomechanical and passive properties of vessels such as diameter and elasticity.

Effects of exercise training on stress-induced vascular reactivity alterations: role of nitric oxide and prostanoids.

Background:Physical exercise may modify biologic stress responses. Objective:To investigate the impact of exercise training on vascular alterations induced by acute stress, focusing on nitric oxide and cyclooxygenase pathways. Method:Wistar rats were separated into: sedentary, trained (60-min swimming, 5 days/week during 8 weeks, carrying a 5% body-weight load), stressed (2 h-immobilization), and trained/stressed. Response curves for noradrenaline, in the absence and presence of L-NAME or indomethacin, were obtained in intact and denuded aortas (n=7-10). Results:None of the procedures altered the denuded aorta reactivity. Intact aortas from stressed, trained, and trained/stressed rats showed similar reduction in noradrenaline maximal responses (sedentary 3.54±0.15, stressed 2.80±0.10*, trained 2.82±0.11*, trained/stressed 2.97± 0.21*, *P<0.05 relate to sedentary). Endothelium removal and L-NAME abolished this hyporeactivity in all experimental groups, except in trained/stressed rats that showed a partial aorta reactivity recovery in L-NAME presence (L-NAME: sedentary 5.23±0,26#, stressed 5.55±0.38#, trained 5.28±0.30#, trained/stressed 4.42±0.41, #P<0.05 related to trained/stressed). Indomethacin determined a decrease in sensitivity (EC50) in intact aortas of trained rats without abolishing the aortal hyporeactivity in trained, stressed, and trained/stressed rats. Conclusions:Exercise-induced vascular adaptive response involved an increase in endothelial vasodilator prostaglandins and nitric oxide. Stress-induced vascular adaptive response involved an increase in endothelial nitric oxide. Beside the involvement of the endothelial nitric oxide pathway, the vascular response of trained/stressed rats involved an additional mechanism yet to be elucidated. These findings advance on the understanding of the vascular processes after exercise and stress alone and in combination.

Alteration of vascular reactivity in heart failure: role of phosphodiesterases 3 and 4.

This study examined the role of the main vascular cAMP-hydrolysing phosphodiesterases (cAMP-PDE) in the regulation of basal vascular tone and relaxation of rat aorta mediated by β-adrenoceptors, following heart failure (HF). Twenty-two weeks after proximal aortic stenosis, to induce HF, or SHAM surgery in rats, we evaluated the expression, activity and function of cAMP-PDE in the descending thoracic aorta. HF rat aortas exhibited signs of endothelial dysfunction, with alterations of the NO pathway, and alteration of PDE3 and PDE4 subtype expression, without changing total aortic cAMP-hydrolytic activity and PDE1, PDE3 and PDE4 activities. Vascular reactivity experiments using PDE inhibitors showed that PDE3 and PDE4 controlled the level of PGF2α -stimulated contraction in SHAM aorta. PDE3 function was partially inhibited by endothelial NO, whereas PDE4 function required a functional endothelium and was under the negative control of PDE3. In HF, PDE3 function was preserved, but its regulation by endothelial NO was altered. PDE4 function was abolished and restored by PDE3 inhibition. In PGF2α -precontracted arteries, β-adrenoceptor stimulation-induced relaxation in SHAM aorta, which was abolished in the absence of functional endothelium, as well as in HF aortas, but restored after PDE3 inhibition in all unresponsive arteries. Our study underlines the key role of the endothelium in controlling the contribution of smooth muscle PDE to contractile function. In HF, endothelial dysfunction had a major effect on PDE3 function and PDE3 inhibition restored a functional relaxation to β-adrenoceptor stimulation.

Loss of lymphocyte‐specific adaptor protein, LNK, aggravates endothelial dysfunction in angiotensin II‐induced hypertension (669.9)

LNK, a lymphocyte‐specific adaptor protein, is a negative regulator of hematopoiesis and endothelial cell signaling. LNK reduces cytokine production and cellular proliferation. Recent genome wide association studies have identified a non‐synonymous single nucleotide polymorphism in LNK that is associated with human hypertension (HTN). We previously found that in mice, loss of LNK is associated with a marked increase in blood pressure and enhanced aortic infiltration of T cells in response to angiotensin II (AngII) infusion. We hypothesized that this HTN is due in part to altered vascular reactivity. LNK‐/‐ and wild type (WT) mice were treated with AngII or vehicle for two weeks and vascular reactivity was assessed. Aortic rings were pre‐constricted with phenylephrine and subsequent relaxations to acetylcholine (Ach) and nitroglycerin (NTG) were examined. Interestingly, relaxation responses to Ach in LNK‐/‐ mice were shifted to the right, indicating impairment of endothelial‐dependent relaxation. The responses to NTG were not significantly altered between LNK‐/‐ and WT aortic rings. Therefore, loss of LNK aggravates endothelial function in the setting of hypertension and may provide one mechanism by which LNK contributes to hypertension and the associated end organ damage. WT Sham WT AngII LNK ‐/‐ Sham LNK ‐/‐ AngII Ach‐Log(EC50) 6.87±0.12 6.60±0.10 6.33±0.11 5.88±0.10 LNK ‐/‐ vs WT p = 0.01; Ang vs Sham p = &lt; 0.0001 Data are mean ± SEM (n = 4‐6)

Tranilast Alleviates Endothelial Dysfunctions and Insulin Resistance via Preserving Glutathione Peroxidase 1 in Rats Fed a High-Fat Emulsion

We investigated the effects of treatment with tranilast on vascular and metabolic dysfunction induced by a high-fat emulsion intragastric administration. Wistar rats were randomized to receive water or high-fat emulsion with or without tranilast treatment (400 mg/kg per day) for 4 weeks. Insulin sensitivity was determined with a hyperinsulinemic-euglycemic clamp experiment and short insulin tolerance test. Vascular reactivity was evaluated using aortic rings in organ chambers. Glutathione peroxidase 1 (GPX1) expressions, eNOS phosphorylation and activity, MCP-1, H2O2 formation, and NO production were determined in vascular or soleus tissues. Tranilast treatment was found to prevent alterations in vascular reactivity and insulin sensitivity and to prevent increases in plasma glucose and insulin noted in the high-fat emulsion-treated rats. These were associated with increased antioxidant enzyme GPX1 expression, eNOS phosphorylation and activity, and NO production, but reductions in H2O2 accumulation. Moreover, tranilast preserved GPX1 expression in palmitic acid (PA)-treated endothelial cells with a consequent decreased ROS formation and increased eNOS phosphorylation and NO production. Therefore, oxidative stress induced by a relatively short-term high-fat diet could cause the early development of vascular and metabolic abnormalities in rats, and tranilast has a beneficial effect in vascular dysfunctions and insulin resistance via preserving GPX1 and alleviating oxidative stress.

PP106—Predictors for the improvement of left ventricular ejection fraction in dilated cardiomyopathy: Results from a cohort from the clinical county hospital CLUJ-napoca

2013 e49 induced relaxation was not changed significantly. The contractile response to Phe significantly increased in arteries that were incubated with ET-1, compared with controls. In addition, PARP-1 and PARP expressions increased significantly in thoracic aorta rings incubated with ET-1. The diminished vasoreactivity in response to ACh and Phe as well as ET-1-related changes in expressions of PARP-1 and PAR were significantly improved by the concomitant incubation with either PEG-SOD plus apocynin, or PJ34. Conclusion: The results of this study suggest that ET-1 causes a significant alteration in vascular reactivity of thoracic artery, and this alteration seems to be via oxidative stress in thoracic artery endothelium with subsequent DNA damage and activation of PARP pathway. Disclosure of Interest: None declared.

Mice Long-Term High-Fat Diet Feeding Recapitulates Human Cardiovascular Alterations: An Animal Model to Study the Early Phases of Diabetic Cardiomyopathy

Background/AimHypercaloric diet ingestion and sedentary lifestyle result in obesity. Metabolic syndrome is a cluster of clinical features secondary to obesity, considered as a pre-diabetic condition and recognized as an independent risk factor for cardiovascular diseases. To better understand the relationship between obesity, metabolic syndrome and cardiovascular disease as well as for the development of novel therapeutic strategies, animal models that reproduce the etiology, course and outcomes of these pathologies are required. The aim of this work was to characterize the long-term effects of high-fat diet-induced obesity on the mice cardiovascular system, in order to make available a new animal model for diabetic cardiomyopathy.Methods/ResultsMale C57BL/6 mice were fed with a standardized high-fat diet (obese) or regular diet (normal) for 16 months. Metabolic syndrome was evaluated testing plasma glucose, triglycerides, cholesterol, insulin, and glucose tolerance. Arterial pressure was measured using a sphygmomanometer (non invasive method) and by hemodynamic parameters (invasive method). Cardiac anatomy was described based on echocardiography and histological studies. Cardiac function was assessed by cardiac catheterization under a stress test. Cardiac remodelling and metabolic biomarkers were assessed by RT-qPCR and immunoblotting. As of month eight, the obese mice were overweight, hyperglycaemic, insulin resistant, hyperinsulinemic and hypercholesterolemic. At month 16, they also presented normal arterial pressure but altered vascular reactivity (vasoconstriction), and cardiac contractility reserve reduction, heart mass increase, cardiomyocyte hypertrophy, cardiac fibrosis, and heart metabolic compensations. By contrast, the normal mice remained healthy throughout the study.ConclusionsMice fed with a high-fat diet for prolonged time recapitulates the etiology, course and outcomes of the early phases of human diabetic cardiomyopathy.

Effects of Reduced Uterine Perfusion Pressure on Cerebral Artery Tone in Pregnant Rats

Preeclampsia is the leading cause of maternal and fetal mortality and it occurs in 5–10% of pregnancies. The etiology of the disease is not well understood but reductions in placental perfusion are central to disease. In patients with preeclampsia (PE) and rodent models of PE alterations in vascular reactivity are indicated. However, the vascular reactivity of the cerebral circulation has not been well characterized, despite the fact that preeclampsia may lead to seizures (eclampsia). We hypothesize that reduced uterine perfusion pressure (RUPP) in pregnant rats, a well accepted model of preeclampsia pathophysiology, will increase vascular reactivity of cerebral arteries isolated from RUPP pregnant rats. For this study, pregnant Sprague Dawley rats were subjected to a surgery to reduce uterine perfusion pressure or a sham operation at gestational day 14. At gestational day 20, cerebral arteries were isolated and studied in an isobaric arteriograph. Active and passive diameters were measured at pressure steps ranging from 25 to 200 mmHg. Our results showed an increase in tone in cerebral arteries of RUPP compared to sham controls (i.e. 12% vs. 6% at 125mmHg). These results support our hypothesis that RUPP surgery in rats can alter cerebral vascular reactivity and allow us to explore the mechanism which may predispose the PE patients to seizures and strokes.

Increased Myogenic Reactivity of Resistance‐Caliber Mesenteric Arteries from Pregnant Rats with Differential Reductions in Uterine Perfusion Pressure: Impact of Thromboxane

Reductions in uterine perfusion pressure are central to the pathogenesis of preeclampsia and may trigger increased production of vasoconstrictor prostanoids such as thromboxane (TX). This may lead to the altered maternal vascular reactivity observed in preeclampsia. The purpose of this study is to determine the impact of TX on resistance artery vascular behavior after reductions in uterine perfusion pressure in gravid rats. Pregnant dams were subjected to periodic (Occluder) and chronic (RUPP) reductions in uterine perfusion pressure on GD 14 and compared to SHAM operated controls. On GD 21, resistance‐sized mesenteric arteries were investigated using a pressurized arteriograph where myogenic reactivity and TX constriction were analyzed. Myogenic reactivity was increased to a similar degree in mesenteric arteries from Occluder and RUPP rats compared to SHAM (p&lt;0.05). Pretreatment of arteries with meclofenamate (non‐specific COX inhibitor) or SQ29548 (TX receptor antagonist) ameliorated the increased myogenic reactivity in Occluder and RUPP arteries (p&lt;0.05). Vasoconstriction with U‐46619 was increased in mesenteric arteries from Occluder and RUPP compared to SHAM (p&lt;0.05). These data provide evidence that the vasoconstrictor prostanoids such as TXA2 at least partially mediates the maternal vascular dysfunction that occurs in response to reduced uterine perfusion during pregnancy.

Cystathionine Gamma‐Lyase Deficiency Impairs H2S Biosynthesis And Vessel Reactivity In Type‐2 Diabetes

Together with the precursor L‐cysteine, cystathionine gamma‐lyase (CSE) is a key enzyme involved in the biosynthesis of hydrogen sulphide (H2S), a potent gaseous vasodilator. Since impaired vasodilation is a hallmark of diabetes the purpose of the current study was to assess the role of H2S in diabetes‐induced vascular dysfunction. Mesenteric arterioles from type‐2 diabetic (db/db) mice were found to express ~30% less CSE protein and 5 fold less CSE mRNA compared to nondiabetic (db/m) controls. In pressure myography experiments, addition of L‐cysteine (1 – 50 μM), to arterioles pre‐contracted with phenylephrine, dose‐dependently induced vasorelaxation in both db/m and db/db vessels, however, the efficacy of L‐cysteine was significantly lower in db/db. The CSE inhibitors D,L‐propargylglycine (PAG) and amino‐oxyacetic acid (AOAA) completely ablated L‐cysteine‐induced relaxation confirming that L‐cysteine operated through the H2S pathway. Incubating db/db vessels overnight with sulforaphane (500 nM), a phytochemical found in cruciferous vegetables, doubled its mRNA level. Taken together, these data suggest that reduced CSE expression and impaired H2S production may contribute to altered vascular reactivity in type‐2 diabetes and hint at the potential for sulforaphane to therapeutically correct H2S deficiency.

Effect of the administration of Solanum nigrum fruit on blood glucose, lipid profiles, and sensitivity of the vascular mesenteric bed to phenylephrine in streptozotocin-induced diabetic rats

BackgroundSolanum nigrum fruit is traditionally used in Asia to manage, control, and treat diabetes but there is no scientific evidence of the efficacy of Solanum nigrum fruit in treatment of diabetes. We designed this study to investigate the effect of the administration of oral doses of aqueous extract from Solanum nigrum fruit on plasma glucose, lipid profiles, and the sensitivity of the vascular mesenteric bed to Phenylephrine in diabetic and non-diabetic rats.Material/MethodsAnimals were divided into 5 groups (n=10): 2 groups served as non-diabetic controls (NDC), and the other groups had diabetes induced with a single injection of streptozotocin (STZ). Solanum nigrum-treated chronic diabetic (CD-SNE) and Solanum nigrum-treated controls (ND-SNE) received 1g/l of Solanum nigrum added to drinking water for 8 weeks. The mesenteric vascular beds were prepared using the McGregor method.ResultsAdministration of Solanum nigrum caused Ca/Mg ratio, plasma glucose, high-density lipoprotein (HDL), low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), total cholesterol, and triglyceride concentrations to return to normal levels, and was shown to decrease alteration in vascular reactivity to vasoconstrictor agents.ConclusionsOur results support the hypothesis that Solanum nigrum could play a role in the management of diabetes and the prevention of vascular complications in STZ-induced diabetic rats.

Impaired Inhibitory Function of Presynaptic A1-Adenosine Receptors in SHR Mesenteric Arteries

In hypertension, vascular reactivity alterations have been attributed to numerous factors, including higher sympathetic innervation/adenosine. This study examined the modulation of adenosine receptors on vascular sympathetic nerves and their putative contribution to higher noradrenaline spillover in hypertension. We assessed adenosine receptors distribution in the adventitia through confocal microscopy, histomorphometry, and their regulatory function on electrically-evoked [3H]-noradrenaline overflow, using selective agonists/antagonists. We found that: i) A1-adenosine receptor agonist (CPA: 100 nM) inhibited tritium overflow to a lower extent in SHR (25% ± 3%, n = 14) compared to WKY (38% ± 3%, n = 14) mesenteric arteries; ii) A2A-adenosine receptor agonist (CGS 21680: 100 nM) induced a slight increase of tritium overflow that was similar in SHR (22% ± 8%, n = 8) and WKY (24% ± 5%, n = 8) mesenteric arteries; iii) A2B- and A3-adenosine receptors did not alter tritium overflow in either strain; iv) all adenosine receptors were present on mesenteric artery sympathetic nerves and/or some adventitial cells of both strains; and v) A1-adenosine receptor staining fractional area was lower in SHR than in WKY mesenteric arteries. We conclude that there is an impaired inhibitory function of vascular presynaptic A1-adenosine receptors in SHR, likely related to a reduced presence of these receptors on sympathetic innervation, which might lead to higher levels of noradrenaline in the synaptic cleft and contribute to hypertension in this strain. [Supplementary Figures: available only at http://dx.doi.org/10.1254/jphs.12266FP]

Heme oxygenase-1 induction protects against hypertension associated with diabetes: effect on exaggerated vascular contractility

Disturbances in vascular reactivity are important components of diabetes-evoked hypertension. Heme oxygenase-1 (HO-1) is a homeostatic enzyme upregulated in stress. This study aims to investigate the protective effect of HO-1 against diabetes-evoked hypertension. Rats were left 8weeks after diabetes induction with streptozotocin to induce vascular dysfunction in the diabetic groups. HO-1 inducers, hemin and curcumin, were daily administrated in the last 6weeks in the treated groups after 2weeks of induction. Then, at the end of the study (8weeks), HO-1 protein level was assessed by immunofluorescence; blood pressure (BP) was recorded; isolated aorta reactivity to phenylephrine (PE) and KCl was studied; reactive oxygen species (ROS) generation was determined; and serum level of glucose, advanced glycation end products (AGEs), and tumor necrosis factor alpha (TNF-α) were determined. While not affected by diabetes, HO-1 protein expression was strongly induced by hemin or curcumin administration. Compared with control animals, diabetes increased systolic and pulse BP. Induction of HO-1 by hemin or curcumin significantly reduced elevated systolic BP and abolished elevated pulse BP without affecting the developed hyperglycemia or AGEs level. The possibility that alterations in vascular reactivity contributed to diabetes-HO-1 BP interaction was investigated. Diabetes increased contractile response of the aorta to PE and KCl, while HO-1 induction by curcumin or hemin prevented aorta-exaggerated response to PE and KCl. Furthermore, the competitive HO inhibitor, tin protoporphyrin, abolished the protective effect of hemin. Diabetes was accompanied with elevated level of TNF-α and ROS generation, while HO-1 induction abrogated increased TNF-α and ROS generation. Collectively, induction of HO-1 protects against hypertension associated with diabetes via ameliorating exaggerated vascular contractility by reducing TNF-α and aortic ROS levels.

Effect of aging on calcium signaling in C57Bl6J mouse cerebral arteries

In cerebral arteries, alterations of vascular reactivity have been observed but not well molecularly characterized. Therefore, we have hypothesized that cerebrovascular reactivity could be modified by aging via a modification of Ca(2+) signaling in smooth muscle cells. Ca(2+) signals and gene expression implicated in contraction have been measured in posterior and middle cerebral arteries from young (2-3 months) and old (20-22 months) C57Bl6/J mice. Aging induced a decrease of KCl- and caffeine-induced contraction as well as a decrease of the amplitudes and an increase of the durations of KCl- and caffeine-induced Ca(2+) signals. These results could be linked with the decrease of gene expression coding for Cav1.2, RyR2, SERCA2, PLB, STIM1, TRIC-B, and the increase of FKBP12.6 and TPCN1 gene expression. Finally, aging induced a modification of InsP3 subtype expression pattern responsible for a modification of the InsP3 affinity to activate Ca(2+) signals. These results show that aging induces a decrease of contractility correlated with modifications of the expression of genes encoding Ca(2+) signaling toolkit. Globally, the amplitude of Ca(2+) signals was decreased, whereas their duration was increased by a defection of Ca(2+) store refilling.

Assessment of Vascular Reactivity in the Peripheral and Coronary Arteries by Cine 3T-Magnetic Resonance Imaging in Young Normotensive Adults after Surgery for Coarctation of the Aorta

This study aimed to investigate whether coarctation of the aorta in infancy indicates an altered vascular reactivity in the peripheral and coronary arteries apart from the secondary effect of hypertension or other complications of the disease. Patients with repaired coarctation of the aorta have a high prevalence of premature cardiovascular complications. The etiology still is not fully understood, and the cause is most likely multifactorial. Endothelial function was assessed by peripheral flow mediated dilation (FMD) and coronary flow reserve (CFR) in a study of 10 control subjects and 10 patients with a successfully repaired coarctation of the aorta (mean age, 20.9 years; 20.5 years after repair). No one had re- or rest-coarctation of the aorta, hypertension, pathologic blood pressure response during exercise, or associated cardiac malformations such as bicuspid aortic valve. CFR was achieved by phase-contrast velocity encoding cine magnetic resonance imaging in the coronary sinus before and during infusion with adenosine (0.14mg/kg/min). FMD was measured in the brachial artery before and after 5min of arterial occlusion. A normal CFR and FMD was found in both groups. Most studies have been conducted with large, unselected groups. The current study group represented the best outcome of the coarctation spectrum (i.e., patients with no evidence of a residual gradient across the coarctation site or systemic hypertension). The findings reassuringly suggest that significant endothelial dysfunction and atherosclerotic changes were not present in this selected cohort.

Thrombospondin-1 in Early Flow-Related Remodeling of Mesenteric Arteries from Young Normotensive and Spontaneously Hypertensive Rats

We tested the hypotheses that TSP-1 participates in the initiation of remodeling of small muscular arteries in response to altered blood flow and that the N-terminal domain of TSP-1 (hepI) can reverse the pathological inward remodeling of resistance arteries from SHR.We measured (1) changes in gene/protein expression in MA of 6 week old WKY and SHR exposed to either increased (+ 100 %) or reduced blood flow (- 90 %) for 24-40 hours and (2) structural changes in MA of 12 week old SHR exposed for 3 days to hepI in organ culture.In both HF and LF of WKY, mRNA expression of eNOS, sGCα1 and PKG1β were significantly reduced (p < 0.05), whereas mRNA of TSP1 was markedly increased (p < 0.05). In MA of young SHR, similar results were obtained except that eNOS mRNA was not reduced in LF. Expression of TSP1 protein was significantly increased in LF of young WKY and SHR (p < 0.05). Exposure of MA of 12 week old SHR to hepI (1 µmol/L) resulted in a rapid lumen diameter increase (+ 12 ± 2% after 3 days) without alteration in vascular reactivity, distensibility, media surface area or cell number.These are the first observations of reduced gene expression of eNOS/sGC/PKG and increased expression of TSP1 at the initiation of arterial remodeling in young WKY and SHR, irrespective of its outward or inward outcome. Furthermore, a fragment of TSP-1 rapidly and directly reversed pathological inward arterial remodeling of SHR in vitro.

Effect of the administration of Psidium guava leaves on blood glucose, lipid profiles and sensitivity of the vascular mesenteric bed to Phenylephrine in streptozotocin-induced diabetic rats

The leaf of Psidium guava is traditionally used in Asia to manage, control and treat diabetes. We designed this study to elucidate the effect of the administration of oral doses of aqueous and ethanol extract from Psidium guava leaves on plasma glucose, lipid profiles and the sensitivity of the vascular mesenteric bed to Phenylephrine in diabetic and non diabetic rats. Animals were divided into 5 groups (n = 10): two groups served as non-diabetic controls (NDC), while the other groups had diabetes induced with a single injection of streptozotocin (STZ). Psidium guavatreated chronic diabetic (PSG-CD) and Psidium guava-treated controls (PSG-C) received 1 g/l of Psidium guava added to the drinking water for 8 weeks. The mesenteric vascular beds were prepared using the McGregor method. Administration of Psidium guava caused Ca/Mg ratio, plasma glucose, high density lipoprotein (HDL), low density lipoprotein (LDL), very low density lipoprotein (VLDL), total cholesterol and triglyceride concentrations to return to normal levels, and was shown to decrease alteration in vascular reactivity to vasoconstrictor agents. Our results support the hypothesis that Psidium guava could play a role in the management of diabetes and the prevention of vascular complications in STZ-induced diabetic rats.

Hot flushes, vascular reactivity and the role of the α-adrenergic system

ABSTRACTBackground Seventy percent of postmenopausal women suffer from hot flushes but the pathophysiology is poorly understood. Proposed mechanisms include altered peripheral vascular reactivity and a narrowed thermoneutral zone. A trigger has not yet been identified; however, the α-adrenergic system, and specifically noradrenaline, has been implicated.Aim To assess the role of the α-adrenergic system by studying the effect of clonidine (α-adrenergic agonist) on flushes and cutaneous microvascular perfusion.Methods Thirty-two postmenopausal women with severe flushing and 14 non-flushing postmenopausal women were recruited. Cutaneous microvascular perfusion was measured using laser Doppler imaging and endothelial function was assessed by iontophoresis (administration of vasoactive agents through the skin by an electric current) of acetylcholine (ACh – endothelium-dependent) and sodium nitroprusside (SNP – endothelium-independent). In a double-blind, longitudinal, cross-over study, clonidine (an α-adrenergic agonist) was compared to placebo in its ability to modulate this response in the flushing group of women.Results The response of the subcutaneous vessels was greater in women who flushed than those who did not (ACh, p < 0.001 and SNP, p = 0.001). However, even though the intensity and number of flushes were decreased by clonidine, there was no difference compared to placebo (p = 0.21) and this ‘placebo effect’ was also noted in perfusion responses (ACh, p = 0.98; SNP, p = 0.50).Conclusion There was a significant ‘placebo effect’ for both clinical response and the reactivity of the subcutaneous vessels, making conclusions regarding the role of the α-adrenergic nervous system in hot flushing difficult to determine at a peripheral level. The mechanism for the change in vascular reactivity remains unclear.