Pressure-Independent Hypertrophy of Veins and Pulmonary Arteries of Spontaneously Hypertensive Rats. Characterization of Function, Structural and Histochemical Changes

1978 ◽  
Vol 55 (s4) ◽  
pp. 31s-36s ◽  
Author(s):  
Stan Greenberg ◽  
Eugene C. Palmer ◽  
Walter M. Wilborn
Keyword(s):  
Smooth Muscle ◽  
Blood Vessels ◽  
Contractile Activity ◽  
Pulmonary Arteries ◽  
Ventricular Myocardium ◽  
Electron Microscopic ◽  
Glycoprotein Synthesis ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Pressure Independent

1. Portal veins, vena cavae and pulmonary arteries from spontaneously hypertensive (SH) rats were found to undergo medial smooth-muscle hypertrophy when compared with corresponding blood vessels from age- and sex-matched Wister—Kyoto (WKy) normotensive rats. There was an increase in the density of the mucopolysaccharide and glycoprotein staining in veins, pulmonary arteries vena venorum and ventricular myocardium of SH rats. 2. Electron-microscopic examination of the blood vessels and myocardium of SH rats suggested enhanced protein synthesis and hypertrophy both in the smooth muscle and endothelial cells. Central venous, portal venous and right ventricular pressures were measured in SH rats and were not elevated when compared with corresponding values for WKy rats. Veins and pulmonary arteries from SH rats developed more tension when challenged with vasoconstrictor stimuli than corresponding vessels obtained from WKy rats. 3. Veins and pulmonary arteries obtained from SH rats demonstrated a greater uptake of [14C]glycosamine than corresponding blood vessels from WKy rats. 4. These findings demonstrate the existence of pressure-independent hypertrophy of smooth muscle in blood vessels obtained from SH rats, associated with an increase in glycoprotein synthesis and an enhanced contractile activity of the muscle. The data suggest that the enhanced contractility of blood vessels from SH rats reflects the enhanced muscle mass. It may represent an aberrant humoral or cellular mechanism which results in the hypertension.

Resolvin D1 reverses reactivity and Ca2+ sensitivity induced by ET-1, TNF-α, and IL-6 in the human pulmonary artery

2014 ◽  
Vol 307 (11) ◽  
pp. H1547-H1558 ◽  
Author(s):  
Roddy Hiram ◽  
Edmond Rizcallah ◽  
Chantal Sirois ◽  
Marco Sirois ◽  
Caroline Morin ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Pulmonary Artery ◽  
Contractile Activity ◽  
Transmembrane Protein ◽  
Pulmonary Arteries ◽  
Resolvin D1 ◽  
Endothelin 1 ◽  
Inflammatory Status ◽  
Tnf Α

Pulmonary hypertension (PH) is a rare and progressive disease characterized by an inflammatory status and vessel wall remodeling, resulting in increased pulmonary artery resistance. During the last decade, treatments have been proposed; most of them target the endothelial pathways that stimulate smooth muscle cell relaxation. However, PH remains associated with significant morbidity. We hypothesized that inflammation plays a crucial role in the severity of the abnormal vasoconstriction in PH. The goal of this study was to assess the effects of resolvin D1 (RvD1), a potent anti-inflammatory agent, on the pharmacological reactivity of human pulmonary arteries (HPAs) via an in vitro model of induced hyperreactivity. The effects of RvD1 and monoacylglyceride compounds were measured on contractile activity and Ca2+ sensitivity developed by HPAs that had been pretreated (or not) under proinflammatory conditions with either 10 ng/ml TNF-α or 10 ng/ml IL-6 or under hyperreactive conditions with 5 nM endothelin-1. The results demonstrated that, compared with controls, 24-h pretreatment with TNF-α, IL-6, or endothelin-1 increased reactivity and Ca2+ sensitivity of HPAs as revealed by agonist challenges with 80 mM KCl, 1 μM serotonin (5-hydroxytryptamine), 30 nM U-46619, and 1 μM phorbol 12,13-dibutyrate. However, 300 nM RvD1 as well as 1 μM monoacylglyceride-docosapentaenoic acid monoglyceride strongly reversed the overresponsiveness induced by both proinflammatory and hyperreactive treatments. In pretreated pulmonary artery smooth muscle cells, Western blot analyses revealed that RvD1 treatment decreased the phosphorylation level of CPI-17 and expression of transmembrane protein member 16A while increasing the detection of G protein-coupled receptor 32. The present data demonstrate that RvD1, a trihydroxylated docosahexaenoic acid derivative, decreases induced overreactivity in HPAs via a reduction in CPI-17 phosphorylation and transmembrane protein member 16A expression.

Primary versus secondary structural changes of the blood vessels in hypertension

1985 ◽  
Vol 63 (4) ◽  
pp. 392-401 ◽  
Author(s):  
Robert M. K. W. Lee ◽  
John S. Smeda
Keyword(s):  
Blood Pressure ◽  
Blood Vessels ◽  
Structural Changes ◽  
Vascular Wall ◽  
Wall Thickening ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto ◽  
Pressure Independent ◽  
Hypertension Development

Various researchers have hypothesized that the thickening of the vascular wall plays an important role in the maintenance of hypertension. Such an alteration can increase the vascular resistance by exerting two effects. A thickened vascular wall could occlude the lumen of the blood vessel and (or) cause the artery to hyperreact to contractile stimuli. Until recently, it has been a general conclusion that such alterations were a secondary adaptation produced by the elevation of blood pressure. Consistent with this view, certain classes of larger arteries do exhibit a thickened vascular wall late during hypertension development and such changes can be prevented from occurring by antihypertensive treatment. However, recent studies involving the mesenteric and renal arteries of Wistar-Kyoto spontaneously hypertensive rats have shown that wall thickening of the vasculature occurs prior to hypertension development and is present even under conditions where the blood pressure has been normalized throughout the animal's life. These latter observations suggest that some structural alterations in the blood vessels observed in hypertension are pressure independent and could be of etiological importance in the initiation of hypertension.

Refined carbohydrate increases blood pressure and catecholamine excretion in SHR and WKY

1986 ◽  
Vol 250 (4) ◽  
pp. E381-E385 ◽  
Author(s):  
R. D. Fournier ◽  
C. C. Chiueh ◽  
I. J. Kopin ◽  
J. J. Knapka ◽  
D. DiPette ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Urinary Excretion ◽  
Blood Vessels ◽  
Strain Differences ◽  
Spontaneously Hypertensive ◽  
Catecholamine Excretion ◽  
Wky Rats ◽  
Shr And Wky Rats

In spontaneously hypertensive (SHR) and normotensive (WKY) rats fed different diets, blood pressure (BP) increased significantly in both strains when the carbohydrate (CHO) source was from refined rather than from natural ingredients. This BP increase was observed whether sucrose, glucose, or starch was the principal CHO. Urinary excretion of norepinephrine, dopamine, and, to some extent, epinephrine also increased, while myocardial concentrations were unaffected. Despite a comparable elevation of catecholamine excretion in both SHR and WKY rats fed high amounts of refined CHO, the BP increases were greater in the former. The strain differences were explained by the known dissimilar response of their blood vessels to catecholamines. The results suggest that BP elevation after high CHO ingestion is mediated via increased catecholamine production and/or release, thus implying a neurogenic mechanism.

Abstract 15: Increased Intrinsic Stiffness of Aortic Vascular Smooth Muscle Cells as a Mechanism for Increased Aortic Stiffness in Spontaneously Hypertensive Rats

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Nancy L Sehgel ◽  
Yi Zhu ◽  
Shumin Gao ◽  
Zhe Sun ◽  
Jerome P Trzeciakowski ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Aortic Stiffness ◽  
Spontaneously Hypertensive Rats ◽  
Shr Rats ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Wky Rats

An increase in vascular stiffness is a fundamental component of hypertension. Our hypothesis is that increased large artery stiffness in hypertension is due in part to intrinsic mechanical properties of vascular smooth muscle cells (VSMC). Adult spontaneously hypertensive rats (SHR) (16 weeks old) and age-matched Wistar-Kyoto normotensive (WKY) rats were studied. Aortic pressure, measured with a Millar catheter, was higher in SHR than WKY (MAP 123±4 versus 96±6 mmHg, p <0.05). Aortic stiffness, measured with pulse wave velocity, in vivo, was 2 to 2.5 fold higher in SHR rats (7.65 mm/ms) compared to normotensive rats(3.27 mm/ms, p<0.01 ). Aortic VSMCs were isolated from the SHR and WKY rats. Stiffness in single VSMC was continuously recorded in vitro using atomic force microscopy and temporal oscillations in VSMC elasticity, which represent the dynamic properties of elasticity, were observed and analyzed by Eigen decomposition. VSMC stiffness was consistently increased by 1.5 to 2 fold in SHR (24.0 kPa) versus WKY (11.8 kPa) ( p<0.05) . Moreover, the oscillations in elasticity were significantly different between the two groups in terms of frequency and amplitude ( p<0.05) . ML-7, a highly specific inhibitor of myosin light chain kinase (MLCK), produced a greater reduction in the VSMC elasticity from SHR aorta compared to WKY rats ( p<0.05 ), and also eliminated the difference between the SHR and WKY. Furthermore, ML-7 altered the oscillation in VSMC elasticity in SHR, but not WKY. These observations indicate that there is an inherently altered VSMC stiffness in hypertension that is associated with unique dynamic cytoskeletal behavior. These dynamic elements may be involved mechanistically in increasing aortic stiffness in SHR rats. MLCK participates in the regulation of VSMC stiffness in hypertension via altering both basal VSMC elasticity and temporal oscillations.

scholarly journals Spontaneously hypertensive rats and platelet Ca2+-ATPases: specific up-regulation of the 97 kDa isoform

1993 ◽  
Vol 295 (3) ◽  
pp. 685-690 ◽  
Author(s):  
B Papp ◽  
E Corvazier ◽  
C Magnier ◽  
T Kovàcs ◽  
N Bourdeau ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Spontaneously Hypertensive Rats ◽  
Human Platelets ◽  
Hypertensive Rats ◽  
Extreme Caution ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Peptide Antibody ◽  
Sds Page ◽  
Wistar Kyoto

The use of platelets instead of smooth muscle cells (SMC) to study the abnormal Ca2+ handling found in hypertension was investigated using spontaneously hypertensive rats (SHR). We studied the regulation of platelet Ca(2+)-ATPases, as we have recently demonstrated that human platelets, like SMC, contain the Ca(2+)-ATPase isoform termed SERCA2-b (sarco-endoplasmic reticulum Ca(2+)-ATPase). In mixed membranes isolated from platelets of normotensive Wistar-Kyoto (WKY) rats and SHR, total Ca(2+)-ATPase activity was found to be 43% higher in SHR than in WKY rats. By the use of autophosphorylation of rat platelet Ca(2+)-ATPases with [gamma-32P]ATP, followed by SDS/PAGE and Western blotting, we found that rat platelets express two distinct Ca(2+)-ATPases: a 100 kDa isoform, recognized by a SERCA2-b-specific anti-peptide antibody, and a 97 kDa isoform, specifically recognized by a polyclonal anti-SERCA antibody. Comparative analysis of platelet membrane Ca(2+)-ATPases from WKY rats and SHR demonstrated that the expression of the SERCA2-b isoform did not change significantly (128 +/- 22%), whereas that of the 97 kDa isoform reached 300 +/- 35% in SHR when compared with WKY rats. We concluded that the upregulation of total platelet Ca(2+)-ATPases in SHR is not due to the 100 kDa SERCA2-b isoform found in SMC, but is specific to the 97 kDa Ca(2+)-ATPase isoform which is not present in SMC. Therefore platelets should be used with extreme caution as a surrogate model of vascular smooth muscle Ca2+ homeostasis.

RhoA-Rho kinase signaling mediates endothelium- and endoperoxide-dependent contractile activities characteristic of hypertensive vascular dysfunction

2010 ◽  
Vol 298 (5) ◽  
pp. H1391-H1405 ◽  
Author(s):  
Steven G. Denniss ◽  
Andrew J. Jeffery ◽  
James W. E. Rush
Keyword(s):  
Contractile Activity ◽  
Vascular Dysfunction ◽  
Rho Kinase ◽  
High Dose ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Wistar Kyoto ◽  
Rock Inhibition ◽  
Dose Dependent ◽  
Cox 1

Hypertensive vasomotor dysfunction is defined by endothelium-dependent contractions involving prostaglandins and ROS. Since both thromboxane-prostanoid receptor (TPr) signaling and ROS activate RhoA-Rho kinase (ROCK) in vascular smooth muscle (VSM) preparations, we hypothesized that enhanced endothelium-dependent contraction in the common carotid artery (CCA) of spontaneously hypertensive rats (SHRs) is ROCK mediated. ACh-stimulated contractions were approximately twofold greater in SHRs versus normotensive Wistar-Kyoto (WKY) rats, abolished by endothelial denudation or cyclooxygenase (COX)-1 inhibition, and nearly eliminated by TPr blockade. RhoA but not ROCK-II protein expression was increased (∼50%) in the SHR CCA. Inhibition of ROCK, but not protein kinase C, caused a dose-dependent reduction in endothelium-dependent contractions to ACh across strains, with the highest dose mirroring the effect of high-dose TPr antagonism. Conversely, ROCK inhibition caused dose-dependent and endothelium- and nitric oxide-independent relaxation in CCAs precontracted with the TPr agonist U-46619. Prostacyclin was the predominant prostaglandin produced by ACh-stimulated CCAs, with greater than twofold more prostacyclin released from SHR versus WKY rats, and its production was unaffected by ROCK inhibition. RhoA activation was approximately twofold higher in quiescent SHR CCAs compared with those from WKY rats and was significantly increased by ACh stimulation. Augmentation of chemical superoxide quenching with tiron or inhibition of the NADPH oxidase-derived superoxide-producing pathway with apocynin reduced ACh-stimulated contractile activity in SHR more than in WKY rats, whereas the SOD mimetic tempol amplified the response. Exposure of CCAs to exogenous H2O2 caused contractions, similar to ACh stimulation, that were greater in SHR than in WKY rats, abolished by COX-1 inhibition, and highly attenuated by TPr blockade or ROCK inhibition. These results indicate that RhoA-ROCK may act as a molecular switch, transducing signals from endothelium-derived prostaglandin(s) and ROS, which are overproduced in SHR CCAs, to “turn on” VSM contractile pathways, thus mediating the enhanced endothelium- and endoperoxide-dependent vascular contractions characteristic of hypertension, among other cardiovascular disease states, such as diabetes and aging.

scholarly journals Hypoxic conditioning in blood vessels and smooth muscle tissues: effects on function, mechanisms, and unknowns

2018 ◽  
Vol 315 (4) ◽  
pp. H756-H770 ◽  
Author(s):  
Asmaa M. Almohanna ◽  
Susan Wray
Keyword(s):  
Smooth Muscle ◽  
Blood Vessels ◽  
Contractile Activity ◽  
Smooth Muscles ◽  
Cell Types ◽  
Hypoxic Preconditioning ◽  
Visceral Organs ◽  
Muscle Tissues ◽  
Force Increase ◽  
Liver And Kidney

Hypoxic preconditioning, the protective effect of brief, intermittent hypoxic or ischemic episodes on subsequent more severe hypoxic episodes, has been known for 30 yr from studies on cardiac muscle. The concept of hypoxic preconditioning has expanded; excitingly, organs beyond the heart, including the brain, liver, and kidney, also benefit. Preconditioning of vascular and visceral smooth muscles has received less attention despite their obvious importance to health. In addition, there has been no attempt to synthesize the literature in this field. Therefore, in addition to overviewing the current understanding of hypoxic conditioning, in the present review, we consider the role of blood vessels in conditioning and explore evidence for conditioning in other smooth muscles. Where possible, we have distinguished effects on myocytes from other cell types in the visceral organs. We found evidence of a pivotal role for blood vessels in conditioning and for conditioning in other smooth muscle, including the bladder, vascular myocytes, and gastrointestinal tract, and a novel response in the uterus of a hypoxic-induced force increase, which helps maintain contractions during labor. To date, however, there are insufficient data to provide a comprehensive or unifying mechanism for smooth muscles or visceral organs and the effects of conditioning on their function. This also means that no firm conclusions can be drawn as to how differences between smooth muscles in metabolic and contractile activity may contribute to conditioning. Therefore, we have suggested what may be general mechanisms of conditioning occurring in all smooth muscles and tabulated tissue-specific mechanistic findings and suggested ideas for further progress.

Diversity of Membrane Abnormalities in Spontaneous Hypertension

1982 ◽  
Vol 63 (s8) ◽  
pp. 27s-29s ◽  
Author(s):  
Y. Yamori ◽  
Y. Nara ◽  
T. Kanbe ◽  
H. Imafuku ◽  
K. Mori ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Ion Concentration ◽  
Membrane Viscosity ◽  
Spontaneously Hypertensive ◽  
Wky Rats ◽  
Low Potassium ◽  
Wistar Kyoto ◽  
Cultured Smooth Muscle Cells

1. The membrane viscosity of erythrocytes and synaptosomal membranes from 3-month-old stroke-prone spontaneously hypertensive rats (SHRSP) was less than that of normotensive Wistar-Kyoto (WKY) rats. 2. The percentage noradrenaline release from synaptosomes in response to a low potassium ion concentration and the incorporation of noradrenaline into synaptosomes were significantly increased in 3-month-old SHRSP compared with WKY rats. 3. Cultured smooth muscle cells obtained from the aorta of SHRSP showed a greater Na+ influx and K+ efflux when Na+, K+-dependent ATPase was inhibited by ouabain than did smooth muscle cells from the aorta of WKY rats. 4. These results suggest that diverse membrane abnormalities are present in SHRSP, including changes in synaptosomal function and the ionic transport and permeability of smooth muscle cells. These changes may be part of the mechanisms of hypertension, whereas the changes in the erythrocytes may serve as genetic markers of hypertension.

Endothelin stimulates protein synthesis in smooth muscle cells

1992 ◽  
Vol 262 (4) ◽  
pp. E412-E416 ◽  
Author(s):  
B. H. Chua ◽  
C. J. Krebs ◽  
C. C. Chua ◽  
C. A. Diglio
Keyword(s):  
Protein Synthesis ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Dna Synthesis ◽  
Muscle Cells ◽  
Spontaneously Hypertensive ◽  
Aortic Smooth Muscle ◽  
Wky Rats ◽  
Protein Kinase C Inhibitor ◽  
Wistar Kyoto

The present work was carried out to assess the effect of endothelin on the relative synthesis of protein, RNA, and DNA in confluent rat aortic smooth muscle cells (SMC) derived from Wistar-Kyoto (WKY) rats maintained under serum-free medium in the presence or absence of insulin, transferrin, and selenium. Insulin stimulated protein synthesis by 42%. Endothelin (1 x 10(-7) M) rapidly induced protein synthesis by 22% (-insulin) and 30% (+insulin). Prior treatment of SMC for 4 h with endothelin resulted in 50% (-insulin) and 38% (+insulin) increase in protein synthesis. The stimulatory effect of endothelin on protein synthesis could be partially blocked by 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine, a protein kinase C inhibitor. Atrial natriuretic factor had no effect on either the basal protein synthesis or protein synthesis stimulated by endothelin. Furthermore, endothelin stimulated RNA synthesis by twofold but had no effect on DNA synthesis in SMC derived from WKY rats. In contrast, SMC derived from spontaneously hypertensive rats showed increased DNA synthesis and cell growth after endothelin stimulation. These studies show that this hormone may play a pivotal role in the development of vascular hypertrophy in hypertension.

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