Hypertensive Arteries Research Articles

Morphometric analysis of structural arrangement of the testial arteries in postresectional arterial pulmonary hypertension

Introduction. Removal of the right or left lung can lead to postresection pulmonary arterial hypertension, venous stasis in the organs of the great circle of blood circulation and structural and functional changes in them. Morphological changes in endothelial cells of arteries of testes in postresection pulmonary arterial hypertension are insufficiently studied.Objective of the research: to study features of structural reorganization of testicular arteries at postresection pulmonary arterial hypertension.Materials of the research and their discussion. Morphological methods were used to study the structural rearrangement of the testicular arteries of 40 rats, which were divided into 3 groups. The 1st group included 11 intact animals, the 2nd - 19 rats with arterial hypertension in the small circulation and compensated pulmonary heart, the 3rd - 10 experimental animals with pulmonary arterial hypertension and decompensated pulmonary heart. Postresection pulmonary arterial hypertension and pulmonary heart were modeled by performing right pulmonectomy in rats. One month after the start of the experiment, rats were euthanized by bloodletting under conditions of thiopental anesthesia. A separate weighing of the chambers of the heart, their planimetry. Pieces were cut from the testicles, which were fixed in 10% formalin solution, passed through ethyl alcohols of increasing concentration and placed in paraffin. Microtome sections after dewaxing were stained with different dyes. In the left and right testes, the outer and inner diameters of small-caliber arteries, media thickness, Kernogan index, endothelial cell height, diameter of their nuclei, nuclear-cytoplasmic ratios in endotheliocytes, and relative volume of damaged cells were measured. Quantitative indicators were processed statistically.Results of the research and their discussion. Morphometrically, it was found that with decompensation of the postresection pulmonary heart, the lumen of the small-caliber arteries of the left testicle decreased by 12.6 %. the Kernogan index - by 11.7 %, and the right - by 9.5 and 9.9 %, respectively. The relative volume of damaged endothelial cells of the studied vessels in right ventricular failure increased 11.6 times, and the right - 9.3 times.Histological examination of the testicles micropreparations of experimental animals after right-sided pulmonectomy showed severe vascular disorders (plethora of mostly venous vessels of the microhemocirculatory tract, stasis, thrombosis, diapedetic perivasal hemorrhage), stromal and perivasal edema, noncystic edema, dystrophy, dystrophy.Conclusions. It is established that in the conditions of the simulated pathology the wall thickens markedly, the lumen of the studied arteries narrows, endotheliocytes are damaged, structural cellular homeostasis is disturbed, which is complicated by their dysfunction, deterioration of blood supply, hypoxia, dystrophic, necrobiotic lesions. Structural changes in the arteries predominated in the left testis and in pulmonary heart decompensation.

Histological and immunohistochemical study of nerve fibers and ganglia in the periarterial adipose tissue of the pulmonary artery bifurcation in patients with and without pulmonary hypertension

Background. One of the possible methods of reducing pressure in the pulmonary artery (PA) in pulmonary hypertension (PH) is radiofrequency damage of the periarterial nerve fibers. At the same time, the impact of the autonomic nervous system has not been fully determined yet. It is also known that dopamine induces LA vasorelaxation, however, the subtypes of dopamine receptors involved in this mechanism have not yet been identified.Objective. To assess the morphology of nerve fibers and ganglia in the periarterial adipose tissue of the PA bifurcation in patients with and without PH. Design and methods. Tissue samples of the PA bifurcation zone with surrounding fatty tissue were taken from 8 patients with PH and 9 patients without PH (autopsy material): 7 women aged 59 ± 22 years and 10 men 62 ± 15 years. An immunohistochemical reaction was performed with antibodies to S100 protein, tyrosine hydroxylase (TH), M1 muscarinic receptor, D1, D2, D5 dopamine receptors. The number of nerve fibers and ganglia per area of the preparation, their diameter and depth relative to the PA intima were estimated.Results. There were no statistically significant differences in the structure and size of nerve fibers and ganglia in patients with and without PH. In general, the average number of nerve fibers per area of the preparation (4 cm2) was 29,1 ± 15,5; ganglia — 1,1 ± 1,3; the average fiber diameter was 130,6 ± 35,1 pm, ganglia — 532,0 ± 790,7 pm; the average fiber-intima distance was 2141,4 ± 663,3 pm, the ganglion-intima — 1799,0 ± 500,5 pm. The density of fibers around the PA bifurcation was significantly higher (p = 0,04) in patients with chronic heart failure (CHF) II NYHA functional class (FC) (20 ± 10 fibers / 4 cm2) compared to patients with CHF III-IV FC (11 ± 4 fibers / 4 cm2). The expression of M1 and TH was determined on nerve fibers and ganglia, in the endothelium and smooth muscle cells of the PA, in the epithelium of the bronchi. At the same time, unlike M1, the expression of TH was not observed in all nerve cells, and its level ranged from 1 to 4 points. No D2 receptor expression was detected, D1 expression was mild, and D5 was 4 points in all cases in the endothelium and smooth muscle cells of the LA.Conclusions. Morphometric analysis of nerve fibers and ganglia revealed no differences between patients with and without PH. There was a significant decrease in the number of nerve fibers with the progression of heart failure. TH expression on nerve fibers and ganglia was less pronounced and was not observed in all cells as compared with the M1 receptor. Expression of dopamine receptors was detected only in the endothelium and smooth muscle cells of the PA. Further morphological study involving larger sample will allow the substantiation for the validity of the interventional innervation of the PA.

A Review of The Properties of The Pulmonary Artery in Pulmonary Arterial Hypertension with Emphasis on The Water Hammer

Sinanis T*1 and Igglezakis D Author Affiliations 1Department of cardiology, Greece 2Department of Production and management engineering, Greece Received: November 18, 2019 | Published: December 02, 2019 Corresponding author: Sinanis T, Department of cardiology, chania general hospital, greece DOI: 10.26717/BJSTR.2019.23.003890

Aerobic exercise-induced inhibition of PKCα/CaV1.2 pathway enhances the vasodilation of mesenteric arteries in hypertension

Regular exercise is regarded as a nonpharmacological therapy for controlling hypertension by improving the function of vascular smooth muscle cells (VSMCs). The underlying mechanism is unclear. L-type-voltage-dependent Ca2+ channel (CaV1.2) on the plasma membrane and PKCα of VSMCs are pivotal modulators of vascular tone. PKCα is hyperactivated and concentrated at the surface membrane during hypertension. This study investigated the effects of aerobic exercise on the PKCα and CaV1.2 in mesenteric arterial smooth muscle cells from spontaneously hypertensive rats (SHRs). SHRs and Wistar-Kyoto (WKY) rats were randomly assigned into sedentary groups (SHR-SED and WKY-SED) and exercise training groups (SHR-EX and WKY-EX). Exercise groups were performed a 12-week moderate-intensity (18–20 m/min) treadmill training. Mesenteric arterial mechanical and functional properties were evaluated. Exercise reduced body weight and systolic blood pressure in both SHR-EX and WKY-EX. PDBu (PKC activator) and BayK 8644 (CaV1.2 agonist) elicited vasoconstriction, while Gö6976 (PKCα inhibitor) and nifedipine (CaV1.2 blocker) induced vasodilation of the vessel rings. In SHRs, exercise normalized the increased vascular sensitivity to these activators and inhibitors. Nifedipine greatly suppressed PDBu-induced vasoconstriction. Upon incubation with Gö6976, the effects of both PDBu and nifedipine were markedly suppressed. In patch-clamp studies, PDBu increased and Gö6976 decreased the CaV1.2 current density. Exercise ameliorated the responses of both PDBu and Gö6976 in SHRs. Immunofluorescence staining suggested that exercise training alleviated the hypertension-induced increase of colocalization rate of PKCα and CaV1.2 α1C subunit in VSMCs. These data indicate that hypertension enhanced PKCα/CaV1.2 pathway-induced constriction of mesenteric arteries, and this pathological enhancement is inhibited by aerobic exercise training.

Aneurysm-type plexiform lesions form in supernumerary arteries in pulmonary arterial hypertension: potential therapeutic implications.

Histological observations in human pulmonary arterial hypertension (PAH) suggest a link between plexiform lesions and pulmonary supernumerary arteries. Pulmonary microvascular endothelial cells are characterized as hyperproliferative and progenitor-like. This study investigates the hypothesis that aneurysm-type plexiform lesions form in pulmonary supernumerary arteries because of their anatomical properties and endothelial characteristics similar to pulmonary microvascular endothelial cells. To induce PAH, rats were injected with Sugen5416, and exposed to hypoxia (10% O2) for 3 days (early stage) or 3 wk (mid-stage), or 3 wk of hypoxia with an additional 10 wk of normoxia (late-stage PAH). We examined morphology of pulmonary vasculature and vascular remodeling in lung serial sections from PAH and normal rats. Aneurysm-type plexiform lesions formed in small side branches of pulmonary arteries with morphological characteristics similar to supernumerary arteries. Over the course of PAH development, the number of Ki67-positive cells increased in small pulmonary arteries, including supernumerary arteries, whereas the number stayed consistently low in large pulmonary arteries. The increase in Ki67-positive cells was delayed in supernumerary arteries compared with small pulmonary arteries. In late-stage PAH, ~90% of small unconventional side branches that were likely to be supernumerary arteries were nearly closed. These results support our hypothesis that supernumerary arteries are the predominant site for aneurysm-type plexiform lesions in Sugen5416/hypoxia/normoxia-exposed PAH rats partly because of the combination of their unique anatomical properties and the hyperproliferative potential of endothelial cells. We propose that the delayed and extensive occlusive lesion formation in supernumerary arteries could be a preventive therapeutic target in patients with PAH.

Sonographic and Doppler Evaluation of Carotid Artery in Hypertension - A Correlative Study with Biochemical Parameters.

Sonographic and Doppler Evaluation of Carotid Artery in Hypertension - A Correlative Study with Biochemical Parameters.

Sonographic assessment of the optic nerve and the central retinal artery in idiopathic intracranial hypertension

PurposeTransorbital sonography easily detects papilledema and enlarged optic nerve sheath diameters (ONSD) in IIH (idiopathic intracranial hypertension) patients. As the central retinal artery is located within the optic nerve, its hemodynamic properties might be affected by the increased pressure. In this study we assessed the diagnostic usefulness of transorbital sonography in IIH with a special focus on color Doppler imaging of the central retinal artery. IIH patients presented papilledema and enlarged ONSD. ONSD accurately predicted an increased intracranial pressure in IIH (cut-off: 5.8 mm, 81% sensitivity, 80% specificity). 24 h following therapeutic lumbar puncture ONSD diminished significantly, whereas papilledema was not changed. PSV (peak systolic velocity) and Vmean (mean flow velocity) of the central retinal artery were increased in IIH patients compared to controls. PSV accurately predicted an increase of intracranial pressure (cut-off: 11.0 cm/s, 70% sensitivity, 69% specificity). PI (pulsatility index), PSV and Vmean decreased following lumbar puncture. PSV and Vmean decreases were statistically significant for right eyes only in which the values changed to normal. In summary, besides ONSD enlargement and papilledema transbulbar sonography demonstrated an alteration of central retinal artery blood flow in IIH patients. Especially PSV might serve as valuable surrogate marker for intracranial pressure in IIH. Furthermore, the change of intra-individual central retinal arteries PI might be a valuable parameter to demonstrate response to lumbar puncture in IIH patients.

Abstract 005: Intensity of Hypertensive Exposure in Young Adulthood and Subclinical Atherosclerosis in Middle Age

Background and aims: To measure the association between intensity of hypertensive exposure and coronary artery calcification (CAC) during a 25-year period in young adulthood. Methods: The Coronary Artery Risk Development in Young Adults (CARDIA) Study enrolled 5,115 healthy black and white American aged 18-30 years at baseline (March 1985-June 1986 to June 2010-May 2011). Durations of hypertension was estimated based on their identification at examinations 7, 10, 15, 20, and 25 years later, and cumulative BP exposure (millimeters of mercury х year) were used to represent long-term exposure to BP levels. CAC was identified by computed tomography (CT) at years 15, 20, and 25. Results: Among 2057 participants at year 0, 30.8% (634 of 2057) developed stage 1 hypertension and 13.8% (284 of 2057) developed stage 2 hypertension. After adjustment, the hazard ratio for the presence CAC was 1.07 (95% CI 0.99, 1.17) and 1.14 (95% CI 1.02, 1.29) times higher for each follow-up years longer duration of stage 1 and stage 2 hypertension respectively. For cumulative BP exposure at year 25, the odds ratio (ORs) for CAC were 1.58 (95% CI 1.39, 1.80) in cumulative SBP, 1.45 (95% CI 1.28, 1.64) in cumulative DBP, 1.26 (95% CI 1.13, 1.41) in cumulative PP, and 1.55 (95% CI 1.36, 1.76) in cumulative MAP for each SD increment. Conclusions: In early adulthood, more severe intensity of hypertensive exposure, durations of hypertension or exposure to BP, is associated with subclinical atherosclerosis in middle age. Key Words: coronary artery calcification, hypertension, young adult

Simvastatin causes pulmonary artery relaxation by blocking smooth muscle ROCK and calcium channels: Evidence for an endothelium-independent mechanism.

Simvastatin reduces pulmonary arterial pressure and right ventricular hypertrophy in animal models of pulmonary arterial hypertension (PAH) and is thought to restore endothelial dysfunction. In vivo effects of drugs are complicated by several factors and little is known of the direct effects of statins on pulmonary arteries. This study investigated the direct effects of simvastatin on pulmonary arteries isolated from rats with or without monocrotaline-induced PAH. Simvastatin suppressed contractions evoked by the thromboxane A2 receptor agonist U46619 (30 nM), the α1–adrenergic agonist phenylephrine (5 μM) and KCl (50 mM) by ~50% in healthy and diseased arteries, but did not reduce contraction evoked by sarco/endoplasmic reticulum ATPase blockers. It relaxed hypertensive arteries in the absence of stimulation. Removing the endothelium or inhibiting eNOS did not prevent the inhibition by simvastatin. Inhibiting RhoA/rho kinase (ROCK) with Y27632 (10 μM) suppressed contractions to U46619 and phenylephrine by ~80% and prevented their inhibition by simvastatin. Y27632 reduced KCl-induced contraction by ~30%, but did not prevent simvastatin inhibition. Simvastatin suppressed Ca2+ entry into smooth muscle cells, as detected by Mn2+ quench of fura-2 fluorescence. The calcium antagonist, nifedipine (1 μM), almost abolished K+-induced contraction with less effect against U46619 and phenylephrine. We conclude that simvastatin relaxes pulmonary arteries by acting on smooth muscle to interfere with signalling through G-protein coupled receptors and voltage-dependent Ca2+ entry. Its actions likely include inhibition of ROCK-dependent Ca2+ sensitisation and voltage-gated Ca2+ channels. These are likely to contribute to the beneficial effects of simvastatin in animal models of PAH.

283Morphometric analysis of internal carotid arteries in hypertensives implementing a semi-automatic measurement platform for magnetic resonance imaging data

283Morphometric analysis of internal carotid arteries in hypertensives implementing a semi-automatic measurement platform for magnetic resonance imaging data

Decreased vasodilatory effect of Tanshinone ⅡA Sodium Sulfonate on mesenteric artery in hypertension

Tanshinone ⅡA Sodium Sulfonate (DS-201), a derivative of traditional Chinese medicinal herb Danshen, has been clinically used for various cardiovascular diseases. Previous studies showed that DS-201 induced vascular relaxation partly due to the activation of the large conductance Ca2+-activated potassium (BKCa) channels. However, the efficacy of DS-201 on the resistant vessels in hypertension remains unknown. Mesentery arteries obtained from spontaneously hypertensive rats (SHR) and hypertension patients were used in this study. The endothelium-denuded mesenteric arteries were prepared to measure the artery tension and evaluate the vasodilatory effect of DS-201. The results showed that DS-201 had a vasodilatory effect on the mesenteric artery rings pre-contracted with either phenylephrine (PE) or thromboxane mimetic U46619 in a concentration-dependent manner. However, the vasodilatory effect of DS-201 significantly decreased in hypertension than in control arteries due to a decrease in protein level of BKCa β1subunit. A BKCa channel blocker IbTX (200 nM) significantly inhibited the relaxant effect of DS-201 on non-hypertensive arteries, whereas the BKCa channel specific agonist NS1619 rescued the vasodilating effects of DS-201 on hypertensive vessels. These results indicate that the vasodilating effect of DS-201 is BKCa-dependent. This study demonstrated that DS-201 alone may not be effective for treating hypertension, but it may be considered as therapy combined with BKCa-agonists or methods rescuing BKCa functions.

Increased caveolin-1 expression enhances the receptor-operated Ca2+ entry in the aorta of two-kidney, one-clip hypertensive rats.

What is the central question of this study? The aim was to examine and compare the contributions of caveolin-1 to the contractile responses mediated by L-type voltage-dependent calcium channels, store-operated Ca2+ channels and receptor-operated Ca2+ channels in two different types of arteries from two-kidney, one-clip hypertensive rats. What is the main finding and its importance? We demonstrated that the density of caveolae and caveolin-1 expression were significantly upregulated in the aorta of two-kidney, one-clip hypertensive rats, but not in the third-order branches of mesenteric arteries. We highlight that caveolin-1 plays an important role in aortic constriction by enhancing receptor-operated Ca2+ entry in the hypertensive rat model. Calcium and its multiple regulatory mechanisms are crucial for the development of hypertension. Among these regulatory mechanisms, store-operated Ca2+ entry (SOCE) and receptor-operated Ca2+ entry (ROCE) mediate agonist-induced calcium influx, contributing to vascular contraction. The SOCE and ROCE are regulated by a variety of mechanisms involving caveolin-1 (Cav1), which has been found to be strongly associated with hypertension in gene polymorphism. In the present study, we investigated the role of Cav1 during the enhanced activity of calcium channels in hypertensive arteries. We demonstrated that the expression level of Cav1 was significantly increased in the aorta of two-kidney, one-clip (2K1C) hypertensive rats. The disruption of caveolae by methyl-β-cyclodextrin did not cause a marked difference in agonist-induced vasoconstriction in the third-order branches of the mesenteric arteries but strongly suppressed the aortic contractile response to endothelin-1 in the 2K1C group, which was not found in the control group. The increase in Cav1 by introduction of Cav1 scaffolding domain enhancing peptide promoted the 1-oleoyl-2-acetyl-glycerol-induced ROCE in hypertensive aortic smooth muscle cells but did not enhance the cyclopiazonic acid-induced SOCE. In the resistance arteries, similar changes were not observed, and no statistical changes of Cav1 expression were evident in the third-order branches of the mesenteric arteries. Our results indicate that increased Cav1 expression might promote the altered [Ca2+ ]i -induced aortic vasoreactivity by enhancing ROCE and be involved in the pathogenesis of hypertension.

NO donors induce vascular relaxation by different cellular mechanisms in hypertensive and normotensive rats

PurposeThis study investigated the intracellular mechanisms involved in the vasodilatation induced by the classic NO donor SNP and the non-classic NO donor cis-[Ru(bpy)2(py)(NO2)](PF6) (or RuBPY) in mesenteric resistance arteries obtained from renal hypertensive (2K-1C) and normotensive (2K) rats. MethodsOn the basis of fluorimetric assays in cultured vascular smooth muscle cells (VSMCs) isolated from 2K-1C and 2K rats, we measured NO release from SNP and RuBPY, cytosolic Ca2+ concentration ([Ca2+]c), and reactive oxygen species (ROS) with the selective probes DAF-2DA, Fluo-3AM and the more selective probe for peroxynitrite (7-CBA), respectively. We determined isometric tension in mesenteric arteries to assess SNP- and RuBPY-induced relaxation. ResultsSNP and RuBPY released NO in comparable amounts in cultured aortic VSMCs from hypertensive 2K-1C and normotensive 2K rats. The NO0 scavenger hydroxocobalamin blunted NO release. Sarco/endoplasmic reticulum Ca2+ ATPase (SERCA) inhibition with thapsigargin reduced [Ca2+]c in normotensive 2K rat VSMCs only. ROS amounts were greater in hypertensive 2K-1C than in normotensive 2K rat VSMCs, but neither SNP nor RuBPY altered ROS concentrations in any of the groups. SNP and RuBPY induced similar relaxation in hypertensive 2K-1C and normotensive 2K rat mesenteric resistance arteries. The SNP and RuBPY-induced relaxation involves sGC and PKG activation. On the other hand, SNP but not RuBPY activates K+ channels. Interestingly, SERCA inhibition reduces SNP induced relaxation only in normotensive 2K rat mesenteric arteries whereas RuBPY-induced relaxation does not involve SERCA activation in both normotensive and hypertensive arteries. ConclusionOur results indicate that SNP and RuBPY-induced mesenteric resistance artery relaxation involves NO/sGC/cGMP/PKG pathway activation. K+ channels and SERCA activation is required to SNP but not for RuBPY-induced relaxation. Moreover, SERCA seems to be impaired in hypertensive 2K-1C rat mesenteric resistance arteries although it does not impact SNP- or RuBPY-induced relaxation.

Working backward: Retrograde balloon angioplasty of atretic arteries in chronic thromboembolic pulmonary hypertension

We describe a patient with chronic thromboembolic pulmonary hypertension who presented to the pediatric cardiac catheterization laboratory for peripheral pulmonary artery recanalization and angioplasty. This case report outlines serial pulmonary arterial rehabilitation via a retrograde approach through intrapulmonary collateral arterial connections.

DIAGNOSTIC VALUE OF STRUCTURAL AND FUNCTIONAL CHANGES IN THE CAROTID AND VERTEBRAL ARTERIES IN ARTERIAL HYPERTENSION, ASSOCIATED WITH BENIGN PAROXYSMAL POSITIONAL VERTIGO

Objective of the study was to assess the diagnostic significance of hemodynamic disorders in the area of carotid and vertebral arteries in patients with hypertension combined with benign paroxysmal positional vertigo (DPPG) using ultrasound duplex scanning of neck vessels. Material and methods . Thirty eight patients of the clinic of Federal Research Center for Fundamental and Translational Medicine with hypertension and concomitant dizziness were examined. The state of carotid and vertebral arteries, blood flow in the arteries were assessed by duplex ultrasound scanning using the Vivid E9 apparatus. Results and discussion. The influence of the blood flow at the level of carotid and vertebral arteries on the severity of clinical symptoms of dizziness in patients with hypertension with concomitant DPPG was shown. The clinical significance of atherosclerotic changes in carotid arteries, tortuosity of carotid and vertebral arteries of the effectiveness of treatment and prevention of dizziness in patients with hypertension and DPPG was revealed. It is shown that in patients with hypertension and comorbid DPP, the severity of the relationship of hemodynamically significant changes in the carotid and vertebral arteries with clinical manifestations of dizziness is greater than in patients with hypertension without DPP. The use of ultrasound duplex scanning of brachiocephalic arteries in hypertension with comorbid vertigo allows for differential diagnosis of benign paroxysmal positional vertigo and cerebrovascular dyscirculatory disorders, the degree of their participation in clinical manifestations of dizziness. A new medical technology for the diagnosis of pathogenic mechanisms of dizziness in patients with hypertension, using ultrasound duplex scanning of carotid and vertebral arteries, allows to personalize treatment and prevention in such patients.

Functional interaction between PDGFβ and GluN2B-containing NMDA receptors in smooth muscle cell proliferation and migration in pulmonary arterial hypertension.

In this study, we explored the complex interactions between platelet-derived growth factor (PDGF) and N-methyl-d-aspartate receptor (NMDAR) and their effect on the excessive proliferation and migration of smooth muscle cells leading to obstructed arteries in pulmonary arterial hypertension (PAH). We report lower expression of glutamate receptor NMDA-type subunit 2B (GluN2B), a subunit composing NMDARs expected to affect cell survival/proliferation of pulmonary artery smooth muscle cells (PASMCs), in PAH patient lungs. PASMC exposure to PDGF-BB stimulated immediate increased levels of phosphorylated Src family kinases (SFKs) together with increased phosphorylated GluN2B (its active form) and cell surface relocalization, suggesting a cross talk between PDGFR-recruited SFKs and NMDAR. Selective inhibition of PDGFR-β or SFKs with imatinib or A-419259, respectively, on one hand, or with specific small-interfering RNAs (siRNAs) on the other hand, aborted PDGF-induced phosphorylation of GluN2B, thus validating the pathway. Selective inhibition of GluN2B using Rö25-6981 and silencing with specific siRNA, in the presence of PDGF-BB, significantly increased both migration and proliferation of PASMCs, thus strengthening the functional importance of the pathway. Together, these results indicate that GluN2B-type NMDAR activation may confer to PASMCs antiproliferative and antimigratory properties. The decreased levels of GluN2B observed in PAH pulmonary arteries could mediate the excessive proliferation of PASMCs, thus contributing to medial hyperplasia and PAH development.

Cardio-diabetology: New subspecialty and collaborative work to defeat the burden of deadly duo

Cardiovascular disease (CVD) is one of the most global threatened diseases; particularly coronary artery disease (CAD) is a major deadly attack around the world. Diabetes mellitus (DM) is associated with a 2 to 4-fold increased mortality risk from heart disease. Diabetes related microvascular complication is seemed to be a hazardous factor for cardiovascular system and likely to cause coronary arteries disease, hypertension, peripheral arteries, and carotid vessels, especially seen in the type 2 DM populations. The severity of cardiovascular complications are related to prolong hyperglycemia and the control of dysglycemia. Thus, effective glycemic control is one of the imperative aspects of the management for the prevention of CVD in diabetes. In addition, different kinds of antidiabetes agents have different mechanism of actions that has impacted to cardiovascular outcome.

TRPV4 activation in rat carotid artery in DOCA hypertension involves eNOS and endothelium-derived contractile factor (EDCF)

ABSTRACTAim: Role of TRPV4 channel in regulation of endothelial function in the carotid artery in deoxycorticosterone acetate (DOCA) model of hypertension in rat was studied.Methods: 8–10 weeks old albino Wistar rats divided into three groups namely Control, UNX and hypertensive animals. Vascular smooth muscle response was studied in isolated carotid artery of rat with acetylcholine, sodium nitroprusside, GSK1016790A (GSK) in presence and absence of L-NAME and indomethacin.Results: At the end of the 6th week, the mean systolic blood pressure was increased in DOCA-treated hypertensive rats (166 ± 8 mm Hg) compared to Control and UNX (125 ± 5 mm Hg). ACh (10–9 to 10–5 M) produced almost 100% relaxation in Control (Emax = 97.48 ± 1.06 %) and UNX animals (Emax = 93.16 ± 2.33 %) which was attenuated in DOCA-treated hypertensive animals (Emax = 70.85 ± 1.65 %). No significant changes seen in SNP (10–12 to 10–5 M) induced relaxation. GSK1016790A (10–12 to 10–7 M)-mediated relaxation was significantly attenuated in DOCA-treated hypertensive animals (Emax = 25.58 ± 13.60%) compared to the control (Emax = 80.59 ± 6.86%) and UNX (Emax = 87.32 ± 2.01%) animals. L-NAME (10–4 M) potently blocked GSK-induced relaxation, and a contractile response to GSK was observed in presence of L-NAME in all the three groups of animals which was sensitive to indomethacin (10–5 M).Conclusion: TRPV4 may regulate the vascular tone of rat carotid artery through an attenuated NO pathway and stimulation of the release of contractile prostanoids in the DOCA hypertensive rats.

Preferential vascular effects of amlodipine in reducing stiffness in muscular not elastic arteries in essential hypertension & the metabolic syndrome

Introduction Arterial stiffness and wave reflection are independent prognosticators of cardiovascular morbidity and mortality. There are two types off arteries in the body; elastic and muscular. The elastic arteries receive the blood directly from the heart while the muscular arteries distribute the blood to various organs of the body. The elasticity of the major arteries decreases with age and therefore may play a key role in the development and control of hypertension and subsequently the choice of drug therapy. The aim of the study is to evaluate the effects of the amlodipine, on arterial stiffness in essential hypertension, compared to hydrochlorothiazide. Methodology We randomised 24 hypertensive patients hypertension (clinic blood pressure (BP) > 140/90 mmHg and ambulatory >135/85 mmHg) to amlodipine 5 mg or hydrochlorothiazide 12.5 mgs in a single blind parallel group study for one month and measured aortic pulse wave velocity (PWV) and augmentation index (AIx) at baseline and one month after treatment. The patients were studied fasting, having abstained from smoking, caffeinated beverages and alcohol 12 h prior to the measurements. Brachial BP and heart rate (Omron), pulse wave velocity (PWV, Complior) and augmentation index (AIx, SphymoCor), a measure of wave reflection, were measured in the supine position after a rest of 15 min. Results were analysed with JMP (SAS for Windows) using Wilcoxon-Rank Sums test and ANOVA. Results are expressed as mean ± SEM, p Results Both drugs produced a similar reduction in brachial BP but there was a greater reduction in the aortic systolic BP (20 ± 3 vs 7 ± 2 mmHg, p Conclusion This short-term study suggests that the effects of amlodipine on arterial stiffness are primarily on muscular rather than elastic arteries. This should be kept in mind when choosing the HTN treatment in elderly and those with diseases affecting the aorta.

Vascular Smooth Muscle Remodeling in Conductive and Resistance Arteries in Hypertension.

Cardiovascular disease is a leading cause of death worldwide and accounts for >17.3 million deaths per year, with an estimated increase in incidence to 23.6 million by 2030. 1 Cardiovascular death represents 31% of all global deaths 2 -with stroke, heart attack, and ruptured aneurysms predominantly contributing to these high mortality rates. A key risk factor for cardiovascular disease is hypertension. Although treatment or reduction in hypertension can prevent the onset of cardiovascular events, existing therapies are only partially effective. A key pathological hallmark of hypertension is increased peripheral vascular resistance because of structural and functional changes in large (conductive) and small (resistance) arteries. In this review, we discuss the clinical implications of vascular remodeling, compare the differences between vascular smooth muscle cell remodeling in conductive and resistance arteries, discuss the genetic factors associated with vascular smooth muscle cell function in hypertensive patients, and provide a prospective assessment of current and future research and pharmacological targets for the treatment of hypertension.