Animal Model Of Hypercholesterolemia Research Articles

Novel Role of Irbesartan in Elevating Serum High Density Lipoprotein in Hypercholesterolemic Animal Model

Objective: To explore the HDL cholesterol-raising capacity of Irbesartan (an antihypertensive drug) in rabbit'sserum.Study Design: Laboratory-based experimental study.Place and Duration of Study: The study was carried out at the Animal House of the National Institute of Health(NIH) Islamabad, Pakistan from January 2023 to November 2023.Methods: This study was conducted on 18 rabbits divided into three groups with six rabbits in each. Leaving one group as a normal control, two out of three groups were made hypercholesterolemic by a high-cholesterol diet. Irbesartan was given to one of the hypercholesteremic groups for 30 days. Blood samples were taken for serum analysis of HDL cholesterol.Results: Results of blood serum levels of all three groups were compared and analyzed on three differentoccasions i.e., on day zero, day 120, and day 150 for HDL cholesterol. Their means were calculated using SPSSVersion 20. The irbesartan-treated group showed obvious elevation in serum HDL cholesterol in comparisonwith the hypercholesteremic control group.Conclusion: It is concluded that Irbesartan, an antihypertensive drug has an additional role of elevating serumhigh-density lipoproteins and can provide the supplementary benefit of improving the lipid profile inhypertension and Hypercholesterolemia. How to cite this: Shakir S, Chaudhry ZR, Atif M, Sadaf R, Chaudhry ER, Chaudhry SR. Novel Role of Irbesartan in Elevating Serum High Density Lipoprotein in Hypercholesterolemic Animal Model. Life and Science. 2024; 5(2): 199-203. doi: http://doi.org/10.37185/LnS.1.1.536

Ultra-High-Resolution Liquid Chromatography Coupled with Electrospray Ionization Quadrupole Time-of-Flight Mass Spectrometry Analysis of Tessaria absinthioides (Hook. & Arn.) DC. (Asteraceae) and Antioxidant and Hypocholesterolemic Properties.

Recently, we reported the chemical profile and the hypocholesterolemic effects of a decoction of Tessaria absinthioides (Hook. & Arn.) DC. (Asteraceae). In this study, we evaluated a methanolic extract (METa) instead. Metabolite profiling was conducted using ultra-high-resolution liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-ESI-QTOF-MS), identifying thirty compounds, including flavonoids, phenolic acids, fatty acids, and phorbolesters. Antioxidant properties were assessed through 2,2-diphenyl-1-picrylhydrazyl (DPPH), Trolox equivalent antioxidant activity (TEAC), ferric-reducing antioxidant power (FRAP), and inhibition of lipid peroxidation in erythrocytes (ILP) assays, exhibiting robust antioxidant activity. The in vivo impact of METa on serum lipid parameters and liver X receptors (LXRs) was evaluated in a hypercholesterolemic animal model. After 14 days on a high-fat diet, male rats received either a vehicle (V) or METa100, METa200 or METa500 (100; 200 and 500 mg METa/kg animal, respectively) for an additional two weeks. METa500 reduced total cholesterol levels (17.62%; p < 0.05) and all doses increased high-density lipoprotein cholesterol levels (METa100: 86.27%; METa200: 48.37%, and METa500: 29.42%; p < 0.0001). However, METa did not alter LXRs expression. The observed antioxidant and hypocholesterolemic properties of METa may be linked to the presence of six di-caffeoylquinic acids. These findings underscore T. absinthioides as a potential candidate for the treatment of metabolic disease.

HMG – CoA reductase inhibition mediated hypocholesterolemic potential of myricetin and quercetin: in-silico and in-vivo studies

ABSTRACT The study was aimed to examine the HMG-CoA reductase (HMGCR) inhibition potential. The in-silico investigations followed the assessments of molecular docking, druggability and molecular dynamics. The molecular dynamics was performed at 100 ns by calculating interaction free energies, RSMD, RSMF, radius of gyration and SASA. Consequently, in-vivo examinations were performed by using a hypercholesterolemic rabbit animal model. The molecular docking showed significant interaction capabilities of myricetin as revealed by binding energy data up to −8.4 Kcal/mol. Accordingly, the data of molecular dynamics i.e. free energy, solvation free energy, radius of gyration, RSMD, RSMF and SASA were shown significant interaction capabilities of myricetin with HMGCR. Supportively, significant ameliorations were made in lipid profile, dyslipidemia indices and oxidative stress by the treatments of myricetin compared to quercetin and atorvastatin. Thus, it can be concluded that myricetin is a potent flavanol with significant potential for HMGCR inhibition and free radical scavenging capability.

The interaction capabilities of phytoconstituents of ethanolic seed extract of cumin (Cuminum cyminum L.) with HMG‐CoA reductase to subside the hypercholesterolemia: A mechanistic approach

AbstractThe aim of this study was to evaluate hypocholesterolemic potential of phytoconstituents of ethanolic seed extract of cumin (Cuminum cyminum L.) by assessments of interaction capabilities with 3‐hydroxy‐3‐methyl‐glutaryl‐coenzyme A reductase (HMG‐CoA) reductase through in vivo and in silico assessments along with screening of phytoconstituents of the test extract. The phytoconstituents of the test extract were identified by Gas chromatography‐mass spectrometry (GC‐MS)/MS examinations. The hypercholesterolemic rabbit animal model was used for in vivo study and further examined the lipid profile and atherogenic indices. The treatments of the test extract and standard drug (atorvastatin) caused significant reductions in dyslipidemia indices, that is, atherogenic index of plasma (AIP), Casteli Risk Index‐I (CRI‐I), CRI‐II and atherogenic coefficient (AC). Accordingly, the molecular docking showed significant interactions between the cuminaldehyde and HMG‐CoA reductase compared to the other phytoconstituents. Further, molecular dynamics (MD) validated the interaction capabilities through assessments of N‐Substance, V‐Volume, T‐Temperature (NVT), N‐Substance, P‐Pressure, T‐Temperature (NPT), Root Mean Score Deviation (RSMD), Root Mean Score Fluctuation (RSMF), radius of gyration, system density, and potential energy along with locality assessment of complex interactions evaluated by angle distribution, average angle interaction, free energy of solvation, and solvent accessible surface area (SASA). Subsequently, the absorption, distribution, metabolism, excretion and toxicity (ADMET) predictions revealed the druggability and bioavailability criteria of the leading identified compounds. On the basis of results obtained, it can be concluded that small phytochemical molecules of test extract of cumin (Cuminum cyminum L.) have capabilities to inhibit the HMG‐CoA reductase and ameliorate the dyslipidemia indices.

Cholesterol-lowering effects of taurine through the reduction of ileal FXR signaling due to the alteration of ileal bile acid composition.

Studies using animal models of hypercholesterolemia have established that taurine reduces cholesterol levels; however, the precise mechanism underlying this cholesterol-lowering effect is unclear. This study addressed this issue by investigating whether bile acid/farnesoid X receptor (FXR) signaling is involved in taurine-mediated cholesterol-lowering effect. Fxr-null and wild-type mice were administered 2% (w/v) taurine in their drinking water and fed a control diet or control diet supplemented with 1% (w/w) cholesterol (cholesterol diet) for 10 days. Taurine intake did not significantly alter hepatic and serum total cholesterol (TC) levels and bile acid compositions of the liver and intestinal lumen in Fxr-null and wild-type mice fed the control diet. By changing to a cholesterol diet, taurine intake significantly decreased hepatic and serum cholesterol levels in wild-type mice. In contrast, it significantly decreased hepatic, not serum, cholesterol levels in Fxr-null mice. Taurine intake significantly altered the bile acid composition of the intestinal lumen in wild-type mice fed a cholesterol diet, but not in Fxr-null mice. An increase in FXR antagonistic bile acids was detected in the intestinal lumen of taurine-treated wild-type mice fed a cholesterol diet. Taurine intake reduced the ileal expression of FXR target genes fibroblast growth factor 15 (Fgf15) and small heterodimer partner (Shp). In contrast, it enhanced the hepatic expression of cholesterol 7α-hydroxylase (Cyp7a1) in wild-type mice fed a cholesterol diet, but not in Fxr-null mice. These results suggest that taurine is partially involved in cholesterol lowering by reducing the ileal FXR signaling due to the alteration of ileal bile acid composition.

Efficacy of Small Molecule Phytochemicals of Petroleum Ether Pod Extract of Prosopis cineraria (L.) Druce on HMG-CoA Reductase and Biomarker Indices of Lipoproteins: In-vitro, In-vivo and In-silico Study

The assigned goals of the study were examined to HMG-CoA reductase inhibition and antioxidants potential of the small molecule phytochemicals of petroleum ether pod extract of Prosopis cineraria (L.) Druce by in-vitro, in-vivo, and in-silico assessments. The phytochemical fingerprinting of the extract was done by LC-MS analysis, and compounds were identified using mass hunter software. In-vitro HMG-CoA reductase assay performed by sigma Aldrich kit. According, in-vivo investigations were conducted by using a hypercholesterolemic rabbit animal model. Further, in-silico analyses of molecular docking and ADMET were conducted by standard protocol. The leading identified compounds, i.e., prosogerin-A, luteolin, and gallic acid, were docked with the target enzyme of HMG-CoA reductase, which demonstrated significant binding energies up to -7.2 to 8.1(Kcal/mol). Subsequently, the ADMET predictions revealed druggability and ideal pharmacokinetics profile. Accordingly, the in-vitro HMG-CoA reductase inhibition assay was showed 53.1% inhibition capability of the test extract. The in-vivo investigation shown that the test extract caused significant reductions in the atherogenic index (log (Total cholesterol/triglyceride), Castelli risk index-I (CRI-I), and Castelli risk -II(CRI-II) along with lipid profile and antioxidants levels. It can be concluded that small-molecule phytochemicals such as Prosogerin A, Luteolin, Gallic acid are present in petroleum ether pod extract of Prosopis cineraria (L.) Druce possesses the capability to subside hypercholesterolemia and ameliorations in biomarker lipoproteins indices through HMG-CoA reductase inhibition and antioxidant potential.

Dill tablet and Ocimum basilicum aqueous extract: Promising therapeutic agents for improving cognitive deficit in hypercholesterolemic rats.

High-cholesterol diet (HCD) is correlated with Alzheimer's disease (AD) and impairment of memory. This study investigated beneficial therapeutic effects of Dill tablet and Ocimum basilicum (Basil) aqueous extract on hypercholesterolemia-induced cognitive deficits and oxidative stress in hippocampus tissues of rats. Hippocampal Aβ(1-42) level was measured. The gene expression levels of superoxide dismutase and inducible-nitric oxide synthase were determined in hippocampus. Cognitive functions were examined and oxidative status was evaluated in serum and hippocampus. Phytochemical properties and in vitro antioxidant activity of Basil extract were assessed. HCD significantly increased serum cholesterol, induced deposition of Aβ plaque, altered hippocampus morphology, and impaired memory function, whereas receiving Basil extract or Dill tablet increased antioxidant potency in serum and hippocampus and normalized HCD-induced deleterious effects. Basil extract and Dill tablet may exhibit their beneficial effects in AD by lowering serum cholesterol and evoking antioxidant system in the brain. PRACTICAL APPLICATIONS: Dill tablet and Basil aqueous extract lowered serum cholesterol in hypercholesterolemic animal models, therefore, they can be used as hypocholesterolemic agents. These edible herbs significantly retarded deposition of Aβ plaque and normalized hippocampal morphology, thus, they favorably protected hippocampus tissue from deleterious effects-induced by hypercholesterolemia. Dill tablet and Basil aqueous extract also corrected oxide-redox balance and normalized HCD-induced oxidative stress to some extent and significantly improved impairments in learning and memory suggesting that these medicinal plants can be considered as surrogate therapeutic agents for the synthetic medicines in the treatment of AD and in postponement of its complications.

Lipid Profiling of Serum and Lipoprotein Fractions in Response to Pitavastatin Using an Animal Model of Familial Hypercholesterolemia.

Statins are widely used for the treatment of atherosclerotic cardiovascular diseases. They inhibit cholesterol biosynthesis in the liver and cause pleiotropic effects, including anti-inflammatory and antioxidant effects. To develop novel therapeutic drugs, the effect of blood-borne lipid molecules on the pleiotropic effects of statins must be elucidated. Myocardial infarction-prone Watanabe heritable hyperlipidemic (WHHLMI) rabbits, an animal model for hypercholesterolemia, are suitable for the determination of lipid molecules in the blood in response to statins because their lipoprotein metabolism is similar to that of humans. Herein, lipid molecules were investigated by lipidome analysis in response to pitavastatin using WHHLMI rabbits. Various lipid molecules in the blood were measured using a supercritical fluid chromatography triple quadrupole mass spectrometry. Cholesterol and cholesterol ester blood concentrations decreased by reducing the secretion of very low density lipoproteins from the liver. Independent of the inhibition effects of cholesterol biosynthesis, the concentrations of some lipids with anti-inflammation and antioxidant effects (phospholipid molecules with n-6 fatty acid side chains, lysophosphatidylcholines, phosphatidylethanolamine plasmalogens, and ceramide molecules) were significantly altered. These findings may lead to further investigation of the mechanism of statin action.

Anti-hypercholesterolemic effect of unripe Musa paradisiaca products on hypercholesterolemia-induced rats

Protective Effects of Vitamin-P and Vitamin-C on Hypercholesterolemia-induced Oxidative Hepatic Damage and Lipid Profile Changes in Female Rats: A Comparative StudyOsama A Alkhamees

Melatonin sirtuin1-dependent mechanism of action in an hypercholesterolemic animal model

Melatonin sirtuin1-dependent mechanism of action in an hypercholesterolemic animal model

Ameliorating effects of D-47, a newly developed compound, on lipid metabolism in an animal model of familial hypercholesterolemia (WHHLMI rabbits)

Improvements induced in lipid metabolism in the liver by D-47, a newly developed compound, were examined herein.WHHLMI rabbits, an animal model of hypercholesterolemia and coronary atherosclerosis, was fed D-47-supplemented chow for 5 weeks at a dose of 30mg/kg. Lipid concentration were assayed using enzymatic methods. Plasma lipoproteins were fractionated with an ultracentrifuge. mRNA expression was analyzed with real-time PCR. Lipidome analyses of lipoproteins were performed using supercritical fluid chromatography mass spectrometry. In the D-47-treated group, serum lipid levels decreased by 23% for total cholesterol and by 40% for triglycerides. These reductions were mainly attributed to decreases in the VLDL fraction. Compared with the control, in the D-47 group, lipid contents in the liver were decreased by 22% in cholesterol and by 69% in triglycerides, and fat accumulation was decreased by 57% in pericardial fat and by 17% in mesenteric fat. In lipidome analyses of VLDL fraction, lysophosphatidylcholine, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylethanolamine plasmalogen, sphingomyelin, and ceramide were decreased by the D-47 treatment. mRNA expression in the liver was 51% lower for FAS and 24% lower for MTP, but 5.9- and 5.1-fold higher for CYP7A1 and CPT-1, respectively, in the D-47 group than in the control. mRNA expression was 72%, 64%, and 36% higher for LPL, CTP-1, and PPARγ, respectively, in mesenteric fat in the D-47 group.D-47 is a potent lipid-lowering compound that uses a different mechanism of action from that of statins. It has potential as a compound in the treatment of steatohepatitis and metabolic syndrome.

A novel compound (D-47), the hypolipidemic effects and the mechanism in an animal model of hypercholesterolemia (WHHLMI rabbit)

A novel compound (D-47), the hypolipidemic effects and the mechanism in an animal model of hypercholesterolemia (WHHLMI rabbit)

Is there an association between hypercholesterolemia and depression? Behavioral evidence from the LDLr−/− mouse experimental model

Although epidemiological studies have reported an association between hypercholesterolemia and mood disorders, there is a lack of data regarding depressive-like behavior in animal models of hypercholesterolemia. To address these questions, we assessed depressive-like behavior and hippocampal and cortical monoaminergic metabolism in three-month-old, low-density lipoprotein receptor knockout (LDLr–/–) and C57BL/6 wild-type mice. The LDLr–/– mice exhibited depressive-like behavior in the sucrose preference test, splash test, and tail suspension test. Increased monoamine oxidase (MAO) A and B activity was evidenced in the hippocampus of LDLr–/– mice. Furthermore, to address whether or not cholesterol modulates MAO activity, we exposed SH-SY5Y human neuroblastoma cells to human isolated low-density lipoprotein (LDL). Notably, LDL increased the activity of MAO-A and stimulated the reactive species generation in vitro. These findings indicate that depressive-like behavior in hypercholesterolemic mice is accompanied by alterations in the monoaminergic metabolism, providing new evidence about the association between hypercholesterolemia and depression.

Effects of dietary Corinthian currants (Vitis vinifera L., var. Apyrena) on atherosclerosis and plasma phenolic compounds during prolonged hypercholesterolemia in New Zealand White rabbits

Corinthian currants are a rich source of phenolic compounds, which are known to exert beneficial effects on cardiovascular disease. The hypothesis tested is whether dietary supplementation with currants attenuates atherosclerosis and affects plasma phenolics during prolonged hypercholesterolemia in rabbits. Thirty New Zealand White rabbits were fed one of four diets (normal and supplemented with 10% currants, with 0.5% cholesterol, and with 0.5% cholesterol plus 10% currants) for eight weeks. Plasma lipids, glucose and hepatic enzymes were determined. Individual phenolic compounds were identified and quantified in plasma during the dietary intervention. At the end of the study, histological examinations of aorta and liver were performed. The high-cholesterol diet resulted in hypercholesterolemia and oxidative stress, increased aspartate aminotransferase (AST) activity and induced aortic and hepatic lesion formation. Corinthian currant supplementation attenuated atherosclerotic lesions, maintained AST within the normal range and reduced oxidative stress without affecting glucose concentrations. The p-OH-benzoic and p-OH-phenylacetic acids predominated at high concentrations in plasma and remained almost constant during the study in the group that received the normal rabbit chow and the groups given food with added cholesterol either alone or supplemented with currants. Currant supplementation to the normal diet resulted in the reduced absorption of phenolic compounds, as revealed by the measurement of their plasma metabolites, suggesting a regulatory mechanism at the gut level under normal conditions.

고콜레스테롤혈증을 유도한 쥐를 대상으로 천년초 추출물의 콜레스테롤 저하 효과

본 연구는 흰쥐를 이용하여 고콜레스테롤 식이로 고콜레스테롤혈증을 유도하고 이에 천년초 추출물을 2, 4% 식이에 포함시켜 경구로 섭취 시의 천년초 추출물의 콜레스레롤 개선 효과를 알아보고자 하였다. 이에 혈중 및 간 조직 내 지질성분, 혈중 간 손상 지표, 분변 내 지질 성분 및 담즙산을 분석하였다. 천년초 추출물 섭취는 고콜레스테롤 식이로 상승된 혈청 총 콜레스테롤과 저밀도 지단백 콜레스테롤을 정상 수준으로 감소시켰으며 고밀도 콜레스테롤은 증가시켜 혈중 콜레스테롤 개선 효과를 나타내었다. 고콜레스테롤 식이 유도로 인해 상승된 혈중 ALT와 AST는 천년초 추출물처치로 감소되는 경향을 보였으며 고콜레스테롤 식이로 인해 상승된 간 조직 내의 총 콜레스테롤과 중성 지방 역시 천년초 추출물 처치로 인해 용량 의존적으로 감소되었다. 분변 내 중성 지방과 담즙산은 천년초 추출물 처치로 유의적으로 상승되어 천년물 추출물 섭취로 중성 지방과 담즙산배설이 유도가 이루어짐을 알 수 있었다. 본 연구 결과 천년초 추출물은 고콜레스테롤 식이로 고콜레스테롤이 유도된 쥐에 있어 콜레스테롤 개선 효과의 가능성 있는 식품 소재로 판단되며, 이를 인체에 적용시키기 위해서는 이에 대한 기전연구와 활성 물질 동정에 대한 계속적인 연구가 이루어져야 할 것으로 생각되어진다.

Aging of brain in hypercholesterolemic mice (ApoE -/-): melatonin receptor distribution

The protective role of melatonin has been investigated [1]. Some studies underlined its significant neuroprotective action with a role in aging processing. In patients with Alzheimer’s Disease, parallel to degenerative tissue changes, there was an overall decrease in the intensity of melatonin receptors in the pineal gland and occipital cortex [2]. Melatonin type 1 (MT1) and type 2 (MT2) receptors disclosed a quite widespread distribution in different brain regions. Recently our group demonstrated that an animal model of hypercholesterolemia, such as ApoE-/- mice, is more susceptible to developing severe liver injury, suggesting that in addition to vascular disease, increased cholesterol products and oxidative stress may also play a role in accelerating aging in the liver [3]. On the basis of this consideration, the aim of our work is to characterize the distribution of MT1 and MT2 in brain of ApoE -/- mice at different age (6 weeks, 16 weeks and 60 weeks) together with senescence markers using immunohistochemical technique to verify the role of these receptors in aging process. The results show an altered distribution of melatonin receptors and synaptic connectivity, indicating a process of aging in ApoE -/- mice and suggesting that melatonin treatment may represent a new approach to reduce brain aging and degeneration.

Investigating the cardio-protective abilities of supplemental L-arginine on parameters of endothelial function in a hypercholesterolemic animal model.

Endothelial dysfunction is now widely recognized as an early marker of cardiovascular disease, making its treatment, or complete avoidance, an emerging, interesting therapeutic target. This study investigated the ability of the highly intriguing amino acid L-arginine to influence endothelial function. Its therapeutic potential is also compared to that of known cardiovascular medications, namely nitroglycerin [a nitric oxide (NO) donor] and enalapril [an angiotensin-converting enzyme (ACE) inhibitor]. Fifty male New Zealand rabbits were included in the study, divided into 5 equal groups: control, hypercholesterolemia (untreated), hypercholesterolemia (+L-arginine), hypercholesterolemia (+enalapril), and hypercholesterolemia (+nitroglycerin). Biochemical investigations included measurement of circulating NOx, malondialdehyde (MDA), and lipid profile markers, as well as dimethylarginine dimethylaminohydrolase (DDAH) and ACE activities. Furthermore, aortic ACE activity and blood platelet aggregation were estimated. A histopathological examination and intimal thickness measurement were also conducted. Compared to the untreated hypercholesterolemic group, all agents were capable of positively influencing MDA levels, platelet aggregation and intimal thickness; however, only the L-arginine group was capable of beneficially and significantly altering both NOx levels and serum and aortic ACE activities. No agents were capable of modulating serum DDAH activity inhibited by hypercholesterolemia. Based on the results of this study, L-arginine appears to be a novel cardio-protective agent, illustrated by its ability to ameliorate the deleterious effects of hypercholesterolemia on endothelial function, in a manner comparable to, and sometimes more potent than, commonly used cardiovascular medications.

Effects of consuming diets containing Agave tequilana dietary fibre and jamaica calyces on body weight gain and redox status in hypercholesterolemic rats

Dietary fibre (DF) obtained from Agave tequilana, which is rich in fructans and insoluble DF, and jamaica calyces (Hibiscus sabdariffa), which is rich in DF and phenolic compounds, were assessed as new potential functional ingredients using the hypercholesterolemic animal model. Wistar rats (200–250g) were divided into 3 groups (n=8) and fed with cholesterol-rich diets supplemented with cellulose (CC, control), agave DF (ADF) or ADF with jamaica calyces (ADF–JC). After consuming the test diets for 5weeks, weight gain in the ADF–JC group was significantly lower than in the other groups. The ADF and ADF–JC groups had a reduced concentration of cholesterol transporters in the caecum tissue, although no changes were observed in the plasma lipid profile. Both treatments improved the redox status by reducing the malondialdehyde serum levels and protein oxidative damage, compared to the CC group. DF from A. tequilana alone, or in combination with jamaica calyces, shows promising potential as a bioactive ingredient.

Cholesterol-lowering Effect of Rice Protein by Enhancing Fecal Excretion of Lipids in Rats

The aim of this study was to investigate the effects of isolated protein from white rice on lipid metabolism in a hypercholesterolemic animal model. Male Sprague-Dawley rats were divided into three groups and fed either a normal diet or a high-cholesterol diet (HCD) containing either casein or isolated rice protein for 4 weeks. Compared with rats fed a HCD with casein, the total cholesterol (TC) level in the plasma was significantly reduced in the rats fed rice protein. However, no significant differences were observed in the triglycerides, high-density lipoprotein (HDL), and glucose levels among the experimental groups. Hepatic total lipids and TC levels were significantly decreased by supplementation with rice protein. In addition, rice protein significantly increased the levels of TC and bile acids in the feces. These results suggest that rice protein may improve HCD-induced hypercholesterolemia by enhancing fecal excretion of cholesterol.

Subservient relationship of the peripheral second systolic pressure peak to the central hemodynamic parameters is preserved, irrespective of atherosclerosis progression in hypercholesterolemic rabbits

We investigated whether the subservient relationship of peripheral to central hemodynamic parameters, such as the augmentation index (AI) and the second systolic (SBP2) and pulse pressures, were preserved with the progression of atherosclerosis in the Kurosawa and Kusanagi-hypercholesterolemic (KHC) rabbit, an animal model for hypercholesterolemia and atherosclerosis. Male KHC rabbits, aged 12 and 24 months, were anesthetized with pentobarbital sodium. Two catheter-tip transducers were introduced to the central (ascending aorta) and peripheral (distal region of the right brachial artery) arteries through the left common carotid and the right radial arteries, respectively. Pressure waves were simultaneously recorded under regular atrial pacing to investigate changes in response to the intravenous infusion of angiotensin II (Ang II) (30-40 ng kg(-1) min(-1)) and sodium nitroprusside (NTP) (20-30 μg kg(-1) min(-1)). Central systolic blood pressure (cSBP) and diastolic blood pressure (DBP), peripheral systolic blood pressure (pSBP) and DBP, and peripheral second systolic blood pressure (pSBP2) showed no significant difference between the 12- and 24-month-old groups before the administration of vasoactive drugs. There was no significant difference in central AI (cAI) between the two age groups before the drug infusion, even though atherosclerosis progressed with aging. Peripheral AI (pAI) changed in parallel with cAI in response to vasopressor and depressor actions due to the infusion of Ang II and NTP, respectively. We conclude that the subservience of pSBP2 to cSBP and pAI to cAI, in addition to the regression relationship of these parameters between peripheral and central arteries, were well preserved, irrespective of the progression of atherosclerosis.