Impaired NO-mediated vasodilation with increased superoxide but robust EDHF function in right ventricular arterial microvessels of pulmonary hypertensive rats

2007 ◽  
Vol 292 (6) ◽  
pp. H2737-H2744 ◽  
Author(s):  
Masahito Kajiya ◽  
Masanori Hirota ◽  
Yousuke Inai ◽  
Takahiko Kiyooka ◽  
Taro Morimoto ◽  
...  
Keyword(s):  
Right Ventricular ◽  
Pressure Overload ◽  
Suppressive Effect ◽  
Protective Role ◽  
Sprague Dawley ◽  
Hypertensive Rats ◽  
Small Arteries ◽  
Sprague Dawley Rats ◽  
Endothelial Nitric Oxide ◽  
Arteriolar Vasodilation

Pulmonary hypertension (PH) causes right ventricular (RV) hypertrophy and, according to the extent of pressure overload, eventual heart failure. We tested the hypothesis that the mechanical stress in PH-RV impairs the vasoreactivity of the RV coronary microvessels of different sizes with increased superoxide levels. Five-week-old male Sprague-Dawley rats were injected with monocrotaline ( n = 126) to induce PH or with saline as controls ( n = 114). After 3 wk, coronary arterioles (diameter = 30–100 μm) and small arteries (diameter = 100–200 μm) in the RV were visualized using intravital videomicroscopy. We evaluated ACh-induced vasodilation alone, in the presence of Nω-nitro-l-arginine methyl ester (l-NAME), in the presence of tetraethylammonium (TEA) or catalase with or without l-NAME, and in the presence of SOD. The degree of suppression in vasodilation by l-NAME and TEA was used as indexes of the contributions of endothelial nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF), respectively. In PH rats, ACh-induced vasodilation was significantly attenuated in both arterioles and small aretries, especially in arterioles. This decreased vasodilation was largely attributable to reduced NO-mediated vasoreactivity, whereas the EDHF-mediated vasodilation was relatively robust. The suppressive effect on arteriolar vasodilation by catalase was similar to TEA in both groups. Superoxide, as measured by lucigenin chemiluminescence, was significantly elevated in the RV tissues in PH. SOD significantly ameliorated the impairment of ACh-induced vasodilation in PH. Robust EDHF function will play a protective role in preserving coronary microvascular homeostasis in the event of NO dysfunction with increased superoxide levels.

scholarly journals The Effects of Healthy Aging on Right Ventricular Structure and Biomechanical Properties: A Pilot Study

2022 ◽  
Vol 8 ◽  
Author(s):  
Danial Sharifi Kia ◽  
Yuanjun Shen ◽  
Timothy N. Bachman ◽  
Elena A. Goncharova ◽  
Kang Kim ◽  
...  
Keyword(s):  
Right Ventricular ◽  
Healthy Aging ◽  
Pressure Overload ◽  
Biomechanical Properties ◽  
Cardiovascular Fitness ◽  
Current Evidence ◽  
Sprague Dawley ◽  
Age Related ◽  
Sprague Dawley Rats ◽  
Peak Pressures

Healthy aging has been associated with alterations in pulmonary vascular and right ventricular (RV) hemodynamics, potentially leading to RV remodeling. Despite the current evidence suggesting an association between aging and alterations in RV function and higher prevalence of pulmonary hypertension in the elderly, limited data exist on age-related differences in RV structure and biomechanics. In this work, we report our preliminary findings on the effects of healthy aging on RV structure, function, and biomechanical properties. Hemodynamic measurements, biaxial mechanical testing, constitutive modeling, and quantitative transmural histological analysis were employed to study two groups of male Sprague-Dawley rats: control (11 weeks) and aging (80 weeks). Aging was associated with increases in RV peak pressures (+17%, p = 0.017), RV contractility (+52%, p = 0.004), and RV wall thickness (+38%, p = 0.001). Longitudinal realignment of RV collagen (16.4°, p = 0.013) and myofibers (14.6°, p = 0.017) were observed with aging, accompanied by transmural cardiomyocyte loss and fibrosis. Aging led to increased RV myofiber stiffness (+141%, p = 0.003), in addition to a bimodal alteration in the biaxial biomechanical properties of the RV free wall, resulting in increased tissue-level stiffness in the low-strain region, while progressing into decreased stiffness at higher strains. Our results demonstrate that healthy aging may modulate RV remodeling via increased peak pressures, cardiomyocyte loss, fibrosis, fiber reorientation, and altered mechanical properties in male Sprague-Dawley rats. Similarities were observed between aging-induced remodeling patterns and those of RV remodeling in pressure overload. These findings may help our understanding of age-related changes in the cardiovascular fitness and response to disease.

Abstract 1135: Hydrogen Peroxide Plays a Crucial Role in Coronary Microvascular Vasodilation with Increased Oxidative Stress in Right Ventricles of Pulmonary Hypertensive Rats

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Masahito Kajiya ◽  
Yousuke Inai ◽  
Taro Morimoto ◽  
Tatsuo Iwasaki ◽  
Kousuke Endo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Crucial Role ◽  
Systolic Pressure ◽  
Sprague Dawley ◽  
Hypertensive Rats ◽  
Small Arteries ◽  
Relative Contribution ◽  
Sprague Dawley Rats

Background: Hydrogen peroxide (H 2 O 2 ) is a well recognized candidate for EDHF. The aim of this study was to examine H 2 O 2 -EDHF function in coronary arterial microvessels under conditions of increased oxidative stress in RV of pulmonary hypertension (PH). Methods: Monocrotaline (60 mg/kg SC) was administrated in 5 week-age male Sprague-Dawley rats to induce PH (PH; n=52). Saline was injected in control rats (n=47). After 3 weeks, RV coronary arterioles (CA; 30 –100 μm) and small arteries (CSA; 100 –200 μm) were visualized in vivo using our intravital videomicroscopy. After cyclooxigenase blockade, Acetylcholine (ACh; 2 μg/kg/min IV) induced vasodilation was evaluated under three conditions; ACh alone, N ω nitro-L-arginine methyl ester (L-NAME), L-NAME+catalase. Differences of percentage vasodilation between ACh alone and L-NAME, and between L-NAME and L-NAME+catalase were used as relative indices for the contributions of NO and H 2 O 2 -EDHF, respectively. Malondialdehyde (MDA) in plasma was measured with colormetric assay. Superoxide production in RV was determined by lucigenin-derived chemiluminescence. Results: RV systolic pressure was significantly increased in PH (75±13 vs. 31±3 mmHg; p<0.05). In PH, Ach-induced vasodilation was significantly reduced in both CA and CSA compared with control (CA; 5.2±1.5% vs. 10.8±3.5%, CSA; 3.8±1.0% vs. 6.0±1.9%, both p<0.05). Inhibition of vasodilation by L-NAME in PH was markedly decreased for both CA (from 4.0% to 1.0%) and CSA (from 3.6% to 1.0%) (both p<0.05). Suppression of vasodilation by the addition of catalase in PH was decreased for CA (from 5.2% to 3.1%, p<0.05), but maintained or even increasing tendency for CSA (from 1.7% to 2.0%, NS). Notably, the relative contribution of H 2 O 2 -EDHF in PH was greatly increased for both CA (from 48% to 60%) and CSA (from 28% to 53%) (both p<0.05). Plasma MDA and RV superoxide in PH were markedly higher than those in control (MDA; 1.63±0.53 vs. 0.93±0.11 μm, superoxide; 290±52 vs 158±25 cpm/mg, both p<0.05). Collectively, increased oxidative stress may augment H 2 O 2 produciton and contribute to the robust EDHF function. Conclusion: Under conditions of increased oxidative stress in PH, H 2 O 2 -EDHF plays a crucial role against NO dysfunction in RV coronary microcirculation.

The Hepatoprotective Role of Warburgia salutaris and Iso-Mukaadial Acetate on Carbon tetrachloride Intoxicated Rats Model

2021 ◽  
Vol 17 ◽  
Author(s):  
Gideon Ayeni ◽  
Mthokozisi Blessing Cedric Simelane ◽  
Shahidul Islam ◽  
Ofentse Jacob Pooe
Keyword(s):  
Carbon Tetrachloride ◽  
Hepatic Injury ◽  
Antioxidant Properties ◽  
Hepatic Necrosis ◽  
Protective Role ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Isolated Compound

Background: Medicinal plants together with their isolated bioactive compounds are known for their antioxidant properties which constitute therapeutic agents that are routinely employed in the treatment of liver diseases. Aims of the Study: The current study sought to explore the protective role of Warburgia salutaris and its isolated compound, iso-mukaadial acetate against carbon tetrachloride (CCl4)-induced hepatic injury. Methods: Thirty-five male Sprague Dawley rats were divided into seven groups of five animals each and injected with CCl4 to induce hepatic injury. Results: Treatment with the crude extract of W. salutaris and of iso-mukaadial acetate significantly reduced the levels of alkaline phosphatase, alanine and aspartate aminotransaminases, total bilirubin and malondialdehyde in a dose dependent manner, when compared to untreated groups. Liver histology revealed a reduction in hepatic necrosis and inflammation. Conclusion: The current investigation has demonstrated that W. salutaris extract and iso-mukaadial acetate could mitigate the acute liver injury inflicted by a hepatotoxic inducer in rats.

scholarly journals Diagnosis of sialodacryoadenitis virus infection of rats in a virulent enzootic outbreak

1981 ◽  
Vol 15 (4) ◽  
pp. 339-342 ◽  
Author(s):  
P. Carthew ◽  
R. P. Slinger
Keyword(s):  
Virus Infection ◽  
Antibody Response ◽  
Clinical Signs ◽  
Sprague Dawley ◽  
Hypertensive Rats ◽  
Natural Conditions ◽  
Breeding Colony ◽  
Serological Screening ◽  
Sprague Dawley Rats ◽  
Natural Outbreak

In a natural outbreak of sialodacryoadenitis virus it was observed that the incidence of clinical signs in spontaneous-hypertensive rats was 100%, and that these signs were of a severity not observed before in other strains of rats. Rats free of the virus were introduced so that the progress of the disease could be studied under natural conditions of spontaneous spread from the enzootically-affected breeding colony. The pathogenesis of the infection in these Sprague-Dawley rats has been recorded over a period of 10 days after their introduction to the colony, and the results of extensive serological screening have shown that the antibody response of the spontaneous-hypertensive rats to the virus is lower than in other strains of rat.

Reduction of chronic hypoxic pulmonary hypertension in the rat by beta-aminopropionitrile

1984 ◽  
Vol 57 (6) ◽  
pp. 1760-1766 ◽  
Author(s):  
J. S. Kerr ◽  
D. J. Riley ◽  
M. M. Frank ◽  
R. L. Trelstad ◽  
H. M. Frankel
Keyword(s):  
Pulmonary Hypertension ◽  
Left Ventricle ◽  
Right Ventricular ◽  
Ventricular Hypertrophy ◽  
Main Pulmonary Artery ◽  
Hydroxyproline Content ◽  
Sprague Dawley ◽  
Hypoxic Pulmonary Hypertension ◽  
Sprague Dawley Rats ◽  
Collagen Accumulation

We administered antifibrotic agent beta-aminopropionitrile (BAPN) to rats exposed to 10% O2-90% N2 for 3 wk to prevent excess vascular collagen accumulation. Groups of Sprague-Dawley rats studied were air breathing, hypoxic, and hypoxic treated with BAPN, 150 mg/kg twice daily intraperitoneally. After the 3-wk period, we measured mean right ventricular pressure (RVP), the ratio of weight of right ventricle to left ventricle plus septum (RV/LV + S), and hydroxyproline content of the main pulmonary artery (PA) trunk. Hypoxia increased RVP from 14 to 29 mmHg; RVP was 21 mmHg in hypoxic BAPN-treated animals. Hypoxia increased the RV/LV + S ratio from 0.28 to 0.41; the ratio was 0.32 in hypoxic BAPN-treated animals. Hypoxia increased PA hydroxyproline from 20 to 239 micrograms/artery; hydroxyproline was 179 micrograms/artery in hypoxic BAPN-treated animals. Thus BAPN prevented pulmonary hypertension, right ventricular hypertrophy, and excess vascular collagen produced by hypoxia. We conclude that vascular collagen contributes to the maintenance of chronic hypoxic pulmonary hypertension.

Orally administered L-arginine does not alter right ventricular hypertrophy in chronically hypoxic rats

1994 ◽  
Vol 266 (2) ◽  
pp. R559-R563 ◽  
Author(s):  
T. C. Resta ◽  
B. R. Walker
Keyword(s):  
Right Ventricular ◽  
Pulmonary Circulation ◽  
Wistar Rats ◽  
Chronic Hypoxia ◽  
Chronic Administration ◽  
Hypoxic Exposure ◽  
Sprague Dawley ◽  
Pulmonary Vasodilation ◽  
Pulmonary Vasodilators ◽  
Sprague Dawley Rats

Evidence suggests that nitric oxide synthesis within the pulmonary circulation may be attenuated during chronic hypoxia in Wistar rats due to reduced L-arginine availability. In contrast, chronically hypoxic Sprague-Dawley rats exhibit normal endothelium-dependent pulmonary vasodilation. The purpose of the present study was to determine whether 1) Wistar rats demonstrate greater right ventricular (RV) hypertrophy in response to chronic hypoxia than Sprague-Dawley rats and 2) chronic administration of L-arginine would diminish this response in Wistar rats. L-Arginine had no effect on the degree of hypoxia-induced RV hypertrophy or polycythemia in either strain of rat. However, Wistar rats demonstrated greater hypoxia-induced RV hypertrophy and polycythemia compared with Sprague-Dawley rats. To determine whether chronically hypoxic Wistar rats indeed exhibit impaired endothelium-dependent pulmonary vasodilation, isolated lungs from control and chronically hypoxic Wistar rats were administered the endothelium-dependent pulmonary vasodilators A23187 or vasopressin. Vasodilatory responses to either agent were unaffected by chronic hypoxic exposure. We conclude that endothelium-dependent pulmonary vasodilation is maintained in the pulmonary circulation of chronically hypoxic Wistar and Sprague-Dawley rats.

Captopril prevents vascular and fibrotic changes but not cardiac hypertrophy in aortic-banded rats

1996 ◽  
Vol 271 (3) ◽  
pp. H906-H913 ◽  
Author(s):  
C. P. Regan ◽  
P. G. Anderson ◽  
S. P. Bishop ◽  
K. H. Berecek
Keyword(s):  
Cardiac Hypertrophy ◽  
Coronary Vessels ◽  
Pressure Overload ◽  
Renin Angiotensin System ◽  
Left Ventricular ◽  
Heart Weight ◽  
Sprague Dawley ◽  
Vessel Morphology ◽  
Sprague Dawley Rats ◽  
Quantitative Image

To determine the role of the renin-angiotensin system (RAS) on cardiovascular remodeling in a pressure overload model of cardiac hypertrophy, a subdiaphragmatic aortic band was placed in adult male, Sprague-Dawley rats. Rats were left untreated (AB) or given captopril (Cap, 400 mg/l) (AB-Cap). Sham-operated controls were either left untreated (S) or given Cap (S-Cap). After 4 wk, rats were catheterized, and carotid and femoral mean arterial pressures (CMAP and FMAP in mmHg, respectively) were recorded. Hearts were isolated, and minimal coronary resistance (MCR) was determined. Hearts were then perfusion fixed, total and regional heart weights were recorded, and sections were processed for vessel morphology. Changes in coronary artery medical thickness and perivascular fibrosis were assessed by quantitative image analysis. CMAP was significantly higher in AB and AB-Cap than S or S-Cap rats (P < 0.05). There was no difference in FMAP in AB vs. S rats, but AB-Cap and S-Cap had lower FMAP values than S rats. Total heart weight and left ventricular weight-to-body weight ratios were increased in AB and AB-Cap rats compared with S and S-Cap rats (P < 0.05). MCR of AB was greater than S and S-Cap rats. MCR of AB-Cap rats was significantly greater than S and S-Cap rats but was significantly less than AB rats. In coronary vessels, medial thickness was greatest in AB, whereas there was no difference among AB-Cap, S, and S-Cap rats. Similarly, the increase in perivascular fibrosis was greatest in AB rats, and there was no difference among AB-Cap, S, and S-Cap rats. These data suggest that the RAS, independent of increased arterial pressure, is critical for the development of the vascular and fibrotic changes that occur in this model of pressure overload hypertrophy.

scholarly journals Rats are protected from the stress of chronic pressure overload compared with mice

2020 ◽  
Vol 318 (5) ◽  
pp. R894-R900 ◽  
Author(s):  
Koichi Nishimura ◽  
Marko Oydanich ◽  
Jie Zhang ◽  
Denis Babici ◽  
Diego Fraidenraich ◽  
...  
Keyword(s):  
Troponin I ◽  
Diastolic Pressure ◽  
Pressure Overload ◽  
Wall Stress ◽  
Left Ventricular ◽  
Pressure Gradients ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Systolic And Diastolic Function ◽  
Systolic Wall Stress

The goal of this investigation was to compare the effects of chronic (4 wk) transverse aortic constriction (TAC) in Sprague-Dawley rats and C57BL/6J mice. TAC, after 1 day, induced similar left ventricular (LV) pressure gradients in both rats ( n = 7) and mice ( n = 7) (113 ± 5.4 vs. 103 ± 11.5 mmHg), and after 4 wk, the percent increase in LV hypertrophy, as reflected by LV/tibial length (51% vs 49%), was similar in rats ( n = 12) and mice ( n = 12). After 4 wk of TAC, LV systolic and diastolic function were preserved in TAC rats. In contrast, in TAC mice, LV ejection fraction decreased by 31% compared with sham, along with increases in LV end-diastolic pressure (153%) and LV systolic wall stress (86%). Angiogenesis, as reflected by Ki67 staining of capillaries, increased more in rats ( n = 6) than in mice ( n = 6; 10 ± 2 vs. 6 ± 1 Ki67-positive cells/field). Myocardial blood flow fell by 55% and coronary reserve by 28% in mice with TAC ( n = 4), but they were preserved in rats ( n = 4). Myogenesis, as reflected by c-kit-positive myocytes staining positively for troponin I, is another mechanism that can confer protection after TAC. However, the c-kit-positive cells in rats with TAC were all negative for troponin I, indicating the absence of myogenesis. Thus, rats showed relative tolerance to severe pressure overload compared with mice, with mechanisms involving angiogenesis but not myogenesis.

scholarly journals The Effect of a Mediterranean Meal on Sprague Dawley Rats DMBA-Induced Mammary Tumors

2010 ◽  
Vol 3 ◽  
pp. CGM.S5894
Author(s):  
Paula C. Pereira ◽  
A. Filipa Vicente ◽  
Maria F. Mesquita ◽  
Antonio S. Cabrita
Keyword(s):  
Experimental Studies ◽  
Protective Role ◽  
Female Rats ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Total Cancer ◽  
Group A ◽  
Histopathologic Analysis ◽  
Group B

The present study intents to find a possible protective role of a Mediterranean type meal on mammary carcinogenesis. Several factors have been associated with breast cancer risk, genetics and environment are the most pointed out in epidemiologic and experimental studies. Diet is an environmental factor that can promote or prevent disease, being responsible for almost 35% of total cancer cases. A total of 72 female rats 50 days old were randomly divided in three groups of 24 rats and housed 4 in each plastic cage in a holding room under constant conditions of 22 ± 2 °C, 55 ± 10% humidity and a 12 h light/dark cycle. All the animals were submitted to the administration of 20 mg of 7, 12 dimethylbenzanthracene (DMBA) in olive oil, by gavages, except group A. The same defined standard food was provided for all the animals in group A and B, supplemented with a Mediterranean meal in group C. All the animals were sacrificed by the end of 150 days. Total carcinoma number did not differ significantly between Groups B and C and there were not found any neoplastic lesions in Group A. Most tumors showed a mixed architectural pattern, with cribriform and papillary areas, comedocarcinoma and necrosis was only seen in Group B. Histopathologic analysis showed that Group C tumors had lower mitotic activity and Pattern Grades, but higher Nuclear Grades. Mediterranean diet type meal showed lower Pattern Grades and lower Mitotic count in spite of that a higher nuclear pleomorphism was also found. Even so, tumors from Group C were better differentiated which can indicate lower malignancy.

Involvement of AT2 receptors at NRVL in tonic baroreflex suppression by endogenous angiotensins

1997 ◽  
Vol 272 (5) ◽  
pp. H2204-H2210 ◽  
Author(s):  
K. S. Lin ◽  
J. Y. Chan ◽  
S. H. Chan
Keyword(s):  
Suppressive Effect ◽  
Angiotensin Receptors ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Inhibitory Modulation ◽  
Sprague Dawley Rats ◽  
Peptide Antagonist ◽  
Endogenous Activity ◽  
At2 Receptors

We evaluated the role of endogenous angiotensin II and III (ANG II and ANG III) at the rostral nucleus reticularis ventrolateralis (NRVL) in the modulation of baroreceptor reflex (BRR) response and the subtype of angiotensin receptors involved in this process. Adult male Sprague-Dawley rats anesthetized and maintained with pentobarbital sodium were used. Exogenous application of ANG II or ANG III (10, 20, or 40 pmol) by bilateral microinjection into the NRVL significantly suppressed the BRR response to transient hypertension induced by phenylephrine (5 micrograms/kg i.v.). The suppressive effect of ANG II (20 pmol) was reversed by an equimolar dose (1.6 nmol) of its peptide antagonist, [Sar1, Ile8]ANG II, and the nonpeptide antagonists for AT1 and AT2 receptors, losartan and PD-123319, respectively. On the other hand, the inhibitory action of ANG III (20 pmol) was blunted by its peptide antagonist. [Ile7]ANG III or PD-123319, but not by losartan. Blocking the endogenous activity of the angiotensins by microinjection into the bilateral NRVL of [Sar1, Ile8]ANG II, [Ile7]ANG III, or PD-123319 elicited an appreciable enhancement of the BRR response, whereas losartan produced minimal effect. These results suggest that, under physiological conditions, both endogenous ANG II and ANG III may exert a tonic inhibitory modulation on the BRR response by acting selectively on the AT2 receptors at the NRVL.

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