scholarly journals Amlodipine Improves Vessel Function and Remodeling in the Lewis Polycystic Kidney Rat Mesenteric Artery

2020 ◽  
Vol 33 (7) ◽  
pp. 634-643
Author(s):  
Ko Jin Quek ◽  
Omar Z Ameer ◽  
Jacqueline K Phillips
Keyword(s):  
Blood Pressure ◽  
Structural Parameters ◽  
Biomechanical Properties ◽  
Resistance Arteries ◽  
Polycystic Kidney ◽  
Artery Wall ◽  
Total N ◽  
Endothelium Dysfunction ◽  
Rat Mesenteric Artery ◽  
Intrinsic Stiffness

Abstract BACKGROUND Hypertension is a common comorbidity associated with chronic kidney disease (CKD). Treatment in these patients often involves L-type Ca2+ channel (LTCC) blockers. The effect of chronic LTCC-blockade treatment on resistance vasculature was investigated in a genetic hypertensive rat model of CKD, the Lewis Polycystic Kidney (LPK) rat. METHODS Mixed-sex LPK and Lewis control rats (total n = 38) were allocated to treated (amlodipine 20 mg/kg/day p.o. from 4 to 18 weeks) and vehicle groups. Following systolic blood pressure and renal function assessment, animals were euthanized and mesenteric vasculature was collected for functional and structural assessment using pressure myography and histology. RESULTS Amlodipine treatment reduced LPK rat blood pressure (untreated vs. treated: 185 ± 5 vs. 165 ± 9 mm Hg; P = 0.019), reduced plasma creatinine (untreated vs. treated: 197 ± 17 vs. 140 ± 16 µmol/l; P = 0.002), and improved some vascular structural parameters (internal and external diameters and wall–lumen ratios); however wall thickness was still increased in LPK relative to Lewis despite treatment (Lewis vs. LPK: 31 ± 2 vs. 41 ± 2 µm, P = 0.047). Treatment improved LPK rats’ endothelium dysfunction, and nitric oxide-dependent and endothelium-derived hyperpolarization vasorelaxation components, and downregulated prostanoid contributions. LTCC blockade had no effect on biomechanical properties of compliance and intrinsic stiffness, nor artery wall composition. CONCLUSIONS Our results indicate that blockade of LTCCs with amlodipine is effective in improving, to a certain extent, detrimental structural and functional vascular features of resistance arteries in CKD.

Abstract TP451: Age-associated Changes in the Structure and Biomechanical Properties of Parenchymal Arterioles

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Janice M Diaz-Otero ◽  
William F Jackson ◽  
Anne M Dorrance
Keyword(s):  
Blood Pressure ◽  
Extracellular Matrix ◽  
Wall Thickness ◽  
Biomechanical Properties ◽  
Wall Structure ◽  
Collagen Deposition ◽  
Artery Wall ◽  
Wall Area ◽  
Age Related ◽  
Artery Remodeling

Arterial aging, a phenomenon that we do not fully understand, results in dysfunctional arteries. Age-associated changes in physiological and vascular functions increase the risk of cardiovascular disease. Aging results in peripheral artery remodeling, described as a change in artery size and wall structure. Age-related cerebral artery remodeling could increase the risk of stroke and vascular dementia particularly in situations where comorbidities, such as hypertension, are present. The effects of aging on the biomechanical properties of parenchymal arterioles (PAs) have not been characterized. PAs regulate perfusion of the cerebral microcirculation and are important in determining cerebrovascular resistance. We hypothesized that aging would decrease the lumen diameter, and increase the wall thickness and collagen deposition in PAs from C57Bl/6 mice. PAs were collected from 3-5 month (young; n=8) and 22-24 month (old; n=8) old male mice for assessment of structure by pressure myography. Data collected at 60mmHg are presented as mean ± SEM, young vs. old. Advanced age was associated with increased systolic blood pressure (126 ± 1 vs 145 ± 2mmHg). Aging did not significantly affect the outer (49 ± 5 vs 53 ± 3μm) or lumen (41 ± 5 vs 41 ± 2μm) diameter of the PAs (p > 0.05 for all comparisons). However, the PAs from older mice had increased wall thickness (4 ± 1 vs 6 ± 1μm), wall area (591 ± 96 vs 853 ± 101μm2), and wall-to-lumen ratio (0.10 ± 0.01 vs 0.13 ± 0.01) (p < 0.05 for all comparisons). Wall stress (302 ± 27 vs 220 ± 11 dynes/cm2) was reduced with age. Changes in artery wall structure have been associated with modifications in the components of the extracellular matrix such as collagen and calcium. The PAs from older mice had increased collagen deposition in the wall (427 ± 172 vs 2699 ± 442μm2; p < 0.05) but the number of arteries with calcium deposits was similar between groups (2 ± 1 vs 3 ± 1 positive vessels/area; p > 0.05). Our studies of geriatric mice with high blood pressure suggest that aging is associated with hypertrophic remodeling of the PAs that is accompanied by alterations in the extracellular matrix of the artery wall; these changes could increase the risk of cerebrovascular diseases.

Simulated microgravity alters rat mesenteric artery vasoconstrictor dynamics through an intracellular Ca2+ release mechanism

2008 ◽  
Vol 294 (5) ◽  
pp. R1577-R1585 ◽  
Author(s):  
Patrick N. Colleran ◽  
Bradley J. Behnke ◽  
M. Keith Wilkerson ◽  
Anthony J. Donato ◽  
Michael D. Delp
Keyword(s):  
Temporal Dynamics ◽  
Orthostatic Intolerance ◽  
Mesenteric Arteries ◽  
Release Mechanism ◽  
Resistance Arteries ◽  
Receptor Mrna ◽  
Cardiovascular Deconditioning ◽  
Rat Mesenteric Artery ◽  
Mrna And Protein Expression

Previous work has shown that orthostatic hypotension associated with cardiovascular deconditioning results from inadequate peripheral vasoconstriction. We used the hindlimb-unloaded (HU) rat in this study as a model to induce cardiovascular deconditioning. The purpose of this study was to test the hypothesis that 14 days of HU diminishes vasoconstrictor responsiveness of mesenteric resistance arteries. Mesenteric resistance arteries from control ( n = 43) and HU ( n = 44) rats were isolated, cannulated, and pressurized to 108 cm H2O for in vitro experimentation. Myogenic (intralumenal pressure ranging from 30 to 180 cm H2O), KCl (2–100 mM), norepinephrine (NE, 10−9–10−4 M) and caffeine (1–20 mM) induced vasoconstriction, as well as the temporal dynamics of vasoconstriction to NE, were determined. The active myogenic and passive pressure responses were unaltered by HU when pressures remained within physiological range. However, vasoconstrictor responses to KCl, NE, and caffeine were diminished by HU, as well as the rate of constriction to NE (C, 14.8 ± 3.6 μm/s vs. HU 7.6 ± 1.8 μm/s). Expression of sarcoplasmic reticulum Ca2+ATPase 2 and ryanodine 3 receptor mRNA was unaffected by HU, while ryanodine 2 receptor mRNA and protein expression were diminished in mesenteric arteries from HU rats. These data suggest that HU-induced and microgravity-associated orthostatic intolerance may be due, in part, to an attenuated vasoconstrictor responsiveness of mesenteric resistance arteries resulting from a diminished ryanodine 2 receptor Ca2+ release mechanism.

scholarly journals Association of erythrocyte n-3 fatty acids with DXA-body fat and cardio-metabolic indices in middle-aged and elderly adults: a prospective study

2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Yuming Chen ◽  
Fang-fang Zeng ◽  
Jie-sheng Lin ◽  
Gengdong Chen ◽  
Ding Ding ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Fatty Acids ◽  
Prospective Study ◽  
Linolenic Acid ◽  
Body Fat ◽  
Fat Mass ◽  
Total N

AbstractIntroductionMany clinical trials showed favorable effects of high-doses supplemental n-3 polyunsaturated fatty acids (PUFA) on cardio-metabolic risk factors. However, limited studies examined the prospective associations of circulating n-3 PUFA with body fat and its distribution, metabolic syndrome (MS), carotid atherosclerosis, and nonalcoholic fatty liver disease (NAFLD) in subjects with habitual diets containing low levels of n-3 PUFA.Materials and MethodsThis community-based prospective study enrolled 4048 participants (40–75 years) at baseline (2008–2010, 2013) from Guangzhou, China. They were followed-up approximately once every 3 years. Fatty acids in erythrocyte membranes were measured at baseline. We determined metabolic syndrome factors, body fat by DXA scanning, carotid intima-media thickness (IMT) and NAFLD by ultrasound at the visits. General information, anthropometric indices, habitual dietary intake and other covariates were assessed at each visit.ResultsAmong the total 4048 subjects, 3075 and 2671 subjects had erythrocyte n-3 PUFA data and completed the first and second follow-ups. Generally, erythrocyte n-3 PUFA were favorably associated with body fat (particularly at abdomen) and its changes, and with the presence and incidence of MS, type 2 diabetes, carotid IMT thickening. The participants with the highest (vs lowest) quartile of n-3 PUFA were associated with -5.81% fat mass (p < 0.001) and -2.11% of fat mass change at the abdomen (Android) area. The adjusted hazards ratios (95% CI) for the highest (vs. lowest) group were 0.74 (0.61, 0.89) (total n-3 PUFA), 0.71 (0.59, 0.86) (docosahexaenoic acid, DHA), 0.78 (0.65, 0.95) (docosapentaenoic acid, DPA), 1.96 (1.60, 2.40) (gamma-linolenic acid, GLA) for MS; 0.70(0.55, 0.90) (total n-3 PUFA), 0.67(0.52,0.87) (DHA) and 0.73(0.57,0.93) (DPA) for bifurcation IMT thickening, 0.57(0.38, 0.86) (eicosapentaenoic acid, EPA) and 0.63 (0.41, 0.95) (DPA) for type 2 diabetes, and 1.18 (1.09, 1.33) (DHA) for alleviated NAFLD. Both higher levels of total and individual marine n-3 PUFAs (DHA, EPA and DPA) were associated with lower blood pressure at baseline and lower changes in diastolic and systolic blood pressure over the follow-up period. Plant n-3 PUFA (α-linolenic acid, ALA) largely had less significant association with the above-mentioned indices as compared with marine n-3 PUFAs.DiscussionHigher proportions of erythrocyte n-3 PUFA (particularly marine sources) was associated with lower body fat, blood pressure and their changes, and lower risks of MS, type 2 diabetes and bifurcation IMT thickening, but higher chance of alleviated NAFLD in middle-aged and older adults.

Indole-3-propionic acid, a tryptophan-derived bacterial metabolite, increases blood pressure via cardiac and vascular mechanisms in rats

2021 ◽  
Author(s):  
Piotr Konopelski ◽  
Dawid Chabowski ◽  
Marta Aleksandrowicz ◽  
Ewa Kozniewska ◽  
Piotr Podsadni ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Propionic Acid ◽  
Metabolic Activity ◽  
Ex Vivo ◽  
Circulatory System ◽  
Cardiovascular Responses ◽  
Gut Bacteria ◽  
Qtc Interval ◽  
Resistance Arteries ◽  
Wistar Kyoto

Objectives. Recent evidence suggests that gut bacteria-derived metabolites interact with the cardiovascular system and alter blood pressure (BP) in mammals. Here, we evaluated the effect of indole-3-propionic acid (IPA), a gut bacteria-derived metabolite of tryptophan, on the circulatory system. Methods. Arterial BP, electrocardiographic and echocardiographic (ECHO) parameters were recorded in male, anesthetized, 12-week-old Wistar-Kyoto rats at baseline and after intravenous administration of either IPA or vehicle. In additional experiments, rats were pretreated with prazosin or pentolinium to evaluate the involvement of the autonomic nervous system in cardiovascular responses to IPA. IPA's concentrations were measured using UHPLC-MS. The reactivity of endothelium-intact and -denuded mesenteric resistance arteries was tested. Cells' viability and LDH cytotoxicity assays were performed on cultured cardiomyocytes. Results. IPA increased BP with a concomitant bradycardic response but no significant change in QTc interval. The pretreatment with prazosin and pentolinium reduced the hypertensive response. ECHO showed increased contractility of the heart after the administration of IPA. Ex vivo, IPA constricted pre-dilated and endothelium-denuded mesenteric resistance arteries and increased metabolic activity of cardiomyocytes. Conclusions. IPA increases BP via cardiac and vascular mechanisms in rats. Furthermore, IPA increases cardiac contractility and metabolic activity of cardiomyocytes. Our study suggests that IPA may act as a mediator between gut microbiota and the circulatory system.

scholarly journals Effects of the Dietary Approaches to Stop Hypertension Diet and Sodium Reduction on Blood Pressure in Persons With Diabetes

Hypertension ◽  
2020 ◽  
Author(s):  
Eva Tseng ◽  
Lawrence J. Appel ◽  
Hsien-Chieh Yeh ◽  
Scott J. Pilla ◽  
Edgar R. Miller ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Dietary Pattern ◽  
Behavioral Interventions ◽  
Small Sample Size ◽  
Small Sample ◽  
Dietary Sodium ◽  
Sodium Reduction ◽  
Dietary Interventions ◽  
Total N ◽  
Intervention Delivery

Elevated blood pressure and blood pressure-related morbidity are extraordinarily common in persons with diabetes. The Dietary Approaches to Stop Hypertension dietary pattern and dietary sodium reduction are recommended as lifestyle interventions in individuals with diabetes. However, these recommendations have largely been based on studies conducted in persons without diabetes. In this review, we summarize available evidence from trials that tested the effects of these 2 dietary interventions on blood pressure in people with diabetes. Overall, of the 3 trials (total n=151) that tested the effects of the Dietary Approaches to Stop Hypertension dietary pattern in persons with diabetes, 2 trials documented that the Dietary Approaches to Stop Hypertension dietary pattern lowered blood pressure. While 16 trials (total n=445) tested the effects of sodium reduction in persons with diabetes, results were inconsistent, likely because of design limitations, for example, brief duration, small sample size, and low baseline blood pressure levels, as well as differences in the mode of intervention delivery (behavioral interventions, feeding studies, and sodium supplements). In conclusion, there is a substantial need for additional research on the blood pressure lowering effects of the Dietary Approaches to Stop Hypertension diet and sodium reduction in people with diabetes and hypertension, given the high prevalence of hypertension and the dearth of high-quality trials in this population.

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