RESUMO
Haemodynamic changes in cerebral circulation are associated with the natural ageing process and associated pathology, leading to the development of incapacitating neurological and neurovascular diseases. Due to inherent biological limitations, current literatures mostly aimed at studying the correlation descriptively or quantifying the relationship in vitro or using computational models. In this paper, a model of a carotid-jugular fistula in the rat was used to create a haemodynamic insult to the intracranial arterial circulation and subsequent venous drainage. An arterial-venous (AV) fistula was created in 12 rats, 6 of which are normotensive Wistar-Kyoto strain (WKY) and the rest spontaneously hypertensive strain (SHR) with an additional 6 in each strains designed as controls without previous surgery. After 4 weeks of convalescence, all 24 rats were euthanised and their cerebral circulation was examined histomorphologically. We confirmed an intrinsic morphological difference between normotensive WKY and hypertensive SHR and found a modest but significant arterial shrinkage in both strains induced with AV fistula. We also reported that alterations in blood flow are also associated with marked extracellular matrix changes. We concluded that the model was suitable for studying the relative contributions of altering haemodynamic patterns and venous drainage on cerebrovascular changes. We also found that hypertension modulated cerebral vascular changes in addition to disrupted blood flow.
Assuntos
Artérias Cerebrais/parasitologia , Hipertensão/fisiopatologia , Fístula Vascular/fisiopatologia , Animais , Hemodinâmica/fisiologia , Ratos , Ratos Endogâmicos WKYRESUMO
PURPOSE: To evaluate the effects of acute arterial blood pressure (ABP) and venous pressure changes on IOP in rats with experimental glaucoma. METHODS: Unilateral experimental ocular hypertension was established in Sprague-Dawley rats by weekly intracameral injection of microbeads. Ocular pulse amplitude (OPA) and IOP were recorded from the anterior chamber using 1.2-Fr microsensors under urethane anesthesia. The effects on IOP during hemodynamic challenges using phenylephrine (PE) (50 µg/kg/min intravenous [IV]) and rapid saline loading (20 mL/kg/min IV) were studied. RESULTS: Over an 8-week period, IOP was significantly elevated by 60% in the unilateral ocular hypertensive eyes. Both ABP and IOP were significantly increased by PE infusion. A significantly greater IOP increase was found in the experimental eyes compared with control eyes (1.32 ± 0.18 mm Hg vs. 0.90 ± 0.09 mm Hg). Correspondingly, higher OPAs and an amplification of the OPA during arterial hypertension were found in the experimental eyes. A sustained rise in IOP secondary to IV saline loading was observed, with a greater rise observed among experimental eyes (0.74 ± 0.13 mm Hg vs. 0.37 ± 0.005 mm Hg). CONCLUSIONS: Sympathetic acceleration of ABP using PE resulted in surges in IOP and OPA. In contrast, increased venous pressure resulted in a more sustained rise in IOP but to a lesser extent. These responses were more pronounced in eyes with experimental glaucoma compared with control eyes, which may reflect the higher starting IOP contributing to a reduced ocular compliance. Our results suggest that eyes with ocular hypertension are more susceptible to IOP variability induced by hemodynamic fluctuations.
Assuntos
Pressão Arterial/fisiologia , Glaucoma/fisiopatologia , Pressão Intraocular/fisiologia , Hipertensão Ocular/fisiopatologia , Pressão Venosa/fisiologia , Análise de Variância , Animais , Modelos Animais de Doenças , Hemodinâmica , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: The effect of brief, prehypertensive therapy by angiotensin-converting enzyme inhibition (ACEi) with perindopril on the structure and function of large arteries was studied in rats. METHODS: Spontaneously hypertensive rats (SHR) received perindopril (3âmg/kg per day) between the ages of either 6 and 10 weeks (early) or 20 and 24 weeks (late) and compared with nonmedicated SHR and normotensive (Wistar-Kyoto) controls (nâ=â6 per group). Haemodynamic parameters and segmental aortic stiffness assessed by pulse wave velocity (PWV) were measured under urethane anaesthesia [1.3âg/kg, intraperitonealy (i.p.)] at 25 weeks. Aortic elastin and collagen content were determined by histomorphometry and calcium content by atomic absorption spectrophotometry. RESULTS: Rats receiving brief, early perindopril therapy had lower tail-cuff SBP than nonmedicated SHR (121â±â1âmmHg, 179â±â5âmmHg, respectively, Pâ<â0.05), reflected in lower thoracic and abdominal aortic pulse pressures. Aortic pulse pressure amplification was lower with early perindopril treatment (early treated 10â±â5%, nonmedicated 20â±â10%, Pâ<â0.05). No blood pressure (BP) differences were observed between late treated and nonmedicated SHR. Isobaric thoracic PWV was lower when treated early but not later in life. Treatment did not alter abdominal PWV. Early treatment was associated with reduction in total aortic calcification (48%, Pâ<â0.001) and reduction in medial cross-sectional area (40%, Pâ<â0.05) of abdominal aorta compared with nonmedicated rats. Treatment increased the wall thickness/diameter ratio, but only early treated rats had a 46% higher elastin/collagen ratio compared with SHR controls. CONCLUSIONS: Early but not late brief ACEi decreased arterial pressure and isobaric wall stiffness in SHR. This was associated with marked alteration of wall structure and the effects persisted after cessation of early treatment. The structural mechanisms responsible for this change varied segmentally along the aortic trunk.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacologia , Aorta/efeitos dos fármacos , Rigidez Vascular , Animais , Aorta/fisiopatologia , Pressão Sanguínea/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Masculino , Perindopril/uso terapêutico , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKYRESUMO
Arterial stiffness, as measured by aortic pulse wave velocity (PWV), is an independent marker of cardiovascular disease and events in both healthy and diseased populations. Although some cardiovascular risk factors, such as age and blood pressure, show a strong association with PWV, the association between heart rate (HR) and PWV is not firmly established. Furthermore, this association has not been investigated at different arterial blood pressures. To study effects of HR on aortic PWV at different mean arterial pressures (MAPs), adult (12 weeks; n=7), male, anesthetized Sprague-Dawley rats were randomly paced at HRs of between 300 and 450 bpm, at 50-bpm steps. At each pacing step, aortic PWV was measured across a physiological MAP range of 60 to 150 mmHg by infusing sodium nitroprusside and phenylephrine. When compared at the same MAP, increases in HR resulted in significant increases in PWV at all of the MAPs >80 mmHg (ANOVA, P<0.05), with the greatest significant change of 6.03±0.93% observed in the range 110 to 130 mmHg. The positive significant association between HR and PWV remained when PWV was adjusted for MAP (ANOVA, P<0.001). These results indicate that HR dependency of PWV is different at higher pressures than at lower pressures and that HR may be a confounding factor that should be taken into consideration when performing analysis based on PWV measurements.
Assuntos
Aorta/fisiologia , Pressão Sanguínea/fisiologia , Frequência Cardíaca/fisiologia , Fluxo Pulsátil/fisiologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Masculino , Modelos Animais , Nitroprussiato/farmacologia , Fenilefrina/farmacologia , Fluxo Pulsátil/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Vasoconstritores/farmacologia , Vasodilatadores/farmacologiaRESUMO
The effect of angiotensin-converting enzyme inhibition on function and structure of the aorta was studied in the Lewis polycystic kidney (LPK) rat model of cystic renal disease and Lewis controls. Pulse-wave velocity (PWV) was recorded under urethane anesthesia (1.3 g/kg ip) in mixed-sex animals aged 6 and 12 wk and in 12-wk-old animals treated with perindopril (3 mg·kg(-1)·day(-1) po) from age 6-12 wk. Tail-cuff systolic pressures were recorded over the treatment period. After PWV measurements, animals were euthanized and the aorta was removed for histomorphological and calcium analysis. Hypertension in LPK at 6 and 12 wk was associated with a shift of the PWV curve upward and to the right, indicating a decrease in aortic compliance, which was significantly reduced by perindopril. LPK demonstrated greater aortic calcification (6 wk: 123 ± 19 vs. 65 ± 7 and 12 wk: 406 ± 6 vs. 67 ± 6 µmol/g, P < 0.001, LPK vs. Lewis, respectively). This was reduced by treatment with perindopril (172 ± 48 µmol/g, 12 wk LPK P < 0.001). Medial cross-sectional area and elastic modulus/wall stress of the aorta were greater in LPK vs. Lewis control animals at 6 and 12 wk of age and showed an age-related increase that was prevented by treatment with perindopril (P < 0.001). Perindopril also ameliorated the degradation of elastin, increase in collagen content, and medial elastocalcinosis seen in 12-wk LPK. Overall, perindopril improved the structural and functional indices of aortic stiffness in the LPK rats, demonstrating a capacity for angiotensin-converting enzyme inhibition to limit vascular remodeling in chronic kidney disease.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacologia , Calcinose/prevenção & controle , Doenças Renais Císticas/patologia , Perindopril/farmacologia , Rigidez Vascular/efeitos dos fármacos , Envelhecimento/fisiologia , Anatomia Transversal , Animais , Artérias/metabolismo , Artérias/fisiopatologia , Pressão Sanguínea/fisiologia , Peso Corporal/fisiologia , Cálcio/metabolismo , Colágeno/metabolismo , Complacência (Medida de Distensibilidade) , Elasticidade/fisiologia , Feminino , Hipertensão Renal/fisiopatologia , Doenças Renais Císticas/complicações , Doenças Renais Císticas/genética , Masculino , RatosRESUMO
Increased aortic pulse-wave velocity (PWV) reflects increased arterial stiffness and is a strong predictor of cardiovascular risk in chronic kidney disease (CKD). We examined functional and structural correlations among PWV, aortic calcification, and vascular remodeling in a rodent model of CKD, the Lewis polycystic kidney (LPK) rat. Hemodynamic parameters and beat-to-beat aortic PWV were recorded in urethane-anesthetized animals [12-wk-old hypertensive female LPK rats (n = 5)] before the onset of end-stage renal disease and their age- and sex-matched normotensive controls (Lewis, n = 6). Animals were euthanized, and the aorta was collected to measure calcium content by atomic absorption spectrophotometry. A separate cohort of animals (n = 5/group) were anesthetized with pentobarbitone sodium and pressure perfused with formalin, and the aorta was collected for histomorphometry, which allowed calculation of aortic wall thickness, medial cross-sectional area (MCSA), elastic modulus (EM), and wall stress (WS), size and density of smooth muscle nuclei, and relative content of lamellae, interlamellae elastin, and collagen. Mean arterial pressure (MAP) and PWV were significantly greater in the LPK compared with Lewis (72 and 33%, respectively) animals. The LPK group had 6.8-fold greater aortic calcification, 38% greater aortic MCSA, 56% greater EM/WS, 13% greater aortic wall thickness, 21% smaller smooth muscle cell area, and 20% less elastin density with no difference in collagen fiber density. These findings demonstrate vascular remodeling and increased calcification with a functional increase in PWV and therefore aortic stiffness in hypertensive LPK rats.