RESUMEN
Many individuals who had coronavirus disease 2019 (COVID-19) develop detrimental persistent symptoms, a condition known as postacute sequelae of COVID-19 (PASC). Despite the elevated risk of cardiovascular disease following COVID-19, limited studies have examined vascular function in PASC with equivocal results reported. Moreover, the role of PASC symptom burden on vascular health has not been examined. We tested the hypothesis that peripheral and cerebral vascular function would be blunted and central arterial stiffness would be elevated in patients with PASC compared with age-matched controls. Furthermore, we hypothesized that impairments in vascular health would be greater in those with higher PASC symptom burden. Resting blood pressure (BP; brachial and central), brachial artery flow-mediated dilation (FMD), forearm reactive hyperemia, carotid-femoral pulse wave velocity (PWV), and cerebral vasodilator function were measured in 12 females with PASC and 11 age-matched female controls without PASC. The severity of persistent symptoms in those with PASC was reported on a scale of 1-10 (higher score: greater severity). Brachial BP (e.g., systolic BP, 126 ± 19 vs.109 ± 8 mmHg; P = 0.010), central BP (P < 0.050), and PWV (7.1 ± 1.2 vs. 6.0 ± 0.8 m/s; P = 0.015) were higher in PASC group compared with controls. However, FMD, reactive hyperemia, and cerebral vasodilator function were not different between groups (P > 0.050 for all). Total symptom burden was not correlated with any measure of cardiovascular health (P > 0.050 for all). Collectively, these findings indicate that BP and central arterial stiffness are elevated in females with PASC, whereas peripheral and cerebral vascular function appear to be unaffected, effects that appear independent of symptom burden.NEW & NOTEWORTHY We demonstrate for the first time that resting blood pressure (BP) and central arterial stiffness are higher in females with PASC compared with controls. In contrast, peripheral and cerebral vascular functions appear unaffected. Moreover, there was no relationship between total PASC symptom burden and measures of BP, arterial stiffness, or vascular function. Collectively, these findings suggest that females with PASC could be at greater risk of developing hypertension, which appears independent of symptom burden.
Asunto(s)
COVID-19 , Hiperemia , Rigidez Vascular , Humanos , Femenino , Análisis de la Onda del Pulso , COVID-19/complicaciones , Presión Sanguínea , Vasodilatadores/farmacología , Arteria BraquialRESUMEN
We assessed hypercapnic cerebrovascular reactivity (CVR) and endothelium-dependent function [cerebral shear-mediated dilation (cSMD)] in the internal carotid artery (ICA) with and without systemic α1-adrenoreceptor blockade via Prazosin. We hypothesized that CVR would be reduced, whereas cSMD would remain unchanged, after Prazosin administration when compared with placebo. In 15 healthy adults (3 female, 26 ± 4 years), we conducted ICA duplex ultrasound during CVR [target +10 mmHg partial pressure of end-tidal carbon dioxide ([Formula: see text]) above baseline, 5 min] and cSMD (+9 mmHg [Formula: see text] above baseline, 30 s) using dynamic end-tidal forcing with and without α1-adrenergic blockade (Prazosin; 0.05 mg/kg) in a placebo-controlled, double-blind, and randomized design. The CVR in the ICA was not different between placebo and Prazosin (P = 0.578). During CVR, the reactivities of mean arterial pressure and cerebrovascular conductance to hypercapnia were also not different between conditions (P = 0.921 and P = 0.664, respectively). During Prazosin, cSMD was lower (1.1 ± 2.0% vs 3.8 ± 3.0%; P = 0.032); however, these data should be interpreted with caution due to the elevated baseline diameter (+1.3 ± 3.6%; condition: P = 0.0498) and lower shear rate (-14.5 ± 23.0%; condition: P < 0.001). Therefore, lower cSMD post α1-adrenoreceptor blockade might not indicate a reduction in cerebral endothelial function per se, but rather, that α1-adrenoreceptors contribute to resting cerebral vascular restraint at the level of the ICA.NEW & NOTEWORTHY We assessed steady-state hypercapnic cerebrovascular reactivity and cerebral endothelium-dependent function, with and without α1-adrenergic blockade (Prazosin), in a placebo-controlled, double-blind, and randomized study, to assess the contribution of α1-adrenergic receptors to cerebrovascular CO2 regulation. After administration of Prazosin, cerebrovascular reactivity to CO2 was not different compared with placebo despite lower blood flow, whereas cerebral endothelium-dependent function was reduced, likely due to elevated baseline internal carotid arterial diameter. These findings suggest that α1-adrenoreceptor activity does not influence cerebral blood flow regulation to CO2 and cerebral endothelial function.
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Arteria Carótida Interna , Hipercapnia , Adulto , Femenino , Humanos , Adrenérgicos , Velocidad del Flujo Sanguíneo/fisiología , Dióxido de Carbono , Arteria Carótida Interna/fisiología , Circulación Cerebrovascular/fisiología , Prazosina/farmacología , Receptores Adrenérgicos alfa 1 , Masculino , Adulto JovenRESUMEN
BACKGROUND: Prenatal exposure to alcohol leads to a greater incidence of many cardiovascular-related diseases, presumably via a mechanism that may involve increased oxidative stress. An agonist of peroxisome proliferator-activated receptor gamma (PPARγ; rosiglitazone) has been shown to suppress alcohol-induced neuroinflammation and oxidative stress. The goal of this study was to determine whether acute and chronic treatment with rosiglitazone could restore or prevent impaired nitric oxide synthase (NOS)-dependent responses of cerebral arterioles in male and female adult (14-16 weeks old) rats exposed to alcohol in utero. METHODS: We fed Sprague-Dawley dams a liquid diet with or without 3% ethanol for the duration of their pregnancy (21-23 days). In the first series of studies, we examined the reactivity of cerebral arterioles to eNOS- (ADP), nNOS-dependent (NMDA), and NOS-independent agonists in male and female adult rats before and during acute (1 hour) topical application of rosiglitazone (1 µM). In a second series of studies, we examined the influence of chronic treatment with rosiglitazone (3 mg/kg/day in drinking water for 2-3 weeks) on the responses of cerebral arterioles in male and female adult rats exposed to alcohol in utero. RESULTS: We found that in utero exposure to alcohol similarly reduced responses of cerebral arterioles to ADP and NMDA, but not to nitroglycerin in male and female adult rats. In addition, acute treatment of the male and female adult rats with rosiglitazone similarly restored this impairment in cerebral vascular function to that observed in controls. We also found that chronic treatment with rosiglitazone prevented impaired vascular function in male and female adult rats that were exposed to alcohol in utero. CONCLUSIONS: PPARγ activation may be an effective and relevant treatment to reverse or prevent cerebral vascular abnormalities associated with prenatal exposure to alcohol.
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Arteriolas/efectos de los fármacos , Encéfalo/irrigación sanguínea , Etanol/administración & dosificación , Óxido Nítrico Sintasa/fisiología , Efectos Tardíos de la Exposición Prenatal , Rosiglitazona/administración & dosificación , Animales , Arteriolas/patología , Arteriolas/fisiopatología , Trastornos Cerebrovasculares/inducido químicamente , Trastornos Cerebrovasculares/fisiopatología , Trastornos Cerebrovasculares/prevención & control , Etanol/efectos adversos , Femenino , Masculino , Estrés Oxidativo/efectos de los fármacos , PPAR gamma/agonistas , Embarazo , Ratas , Ratas Sprague-Dawley , Superóxidos/análisisRESUMEN
BACKGROUND: Maternal consumption of alcohol produces abnormalities in the developing fetus and can contribute to an increased incidence of many cardiovascular-related diseases. The first goal of this study was to determine whether in utero exposure to alcohol influences reactivity of cerebral arterioles in adult (12 to 15 weeks old) rats. The second goal of this study was to examine whether in utero exposure to alcohol increased the susceptibility of the brain to damage following an ischemic event in adult rats. METHODS: We fed Sprague Dawley dams a liquid diet with or without alcohol (3% ethanol) for the duration of their pregnancy (21 to 23 days). In the first series of studies, we examined reactivity of cerebral arterioles to endothelial nitric oxide synthase (eNOS)- (adenosine diphosphate [ADP]) and neuronal nitric oxide synthase (nNOS)-dependent N-methyl-D-aspartate (NMDA, and NOS-independent agonists in adult rats before and during application of l-NMMA. In another series of studies, we examined infarct volume following middle cerebral artery occlusion in adult offspring exposed to alcohol in utero. In both series of studies, we also determined the role for an increase in oxidative stress by feeding dams apocynin for the duration of their pregnancy. RESULTS: We found that in utero exposure to alcohol reduced responses of cerebral arterioles to ADP and NMDA, but not to nitroglycerin in adult rats. In addition, treatment of the dams with apocynin prevented this impairment in cerebral vascular function. We also found that in utero exposure to alcohol worsened brain damage following ischemia/reperfusion in adult rats and that treatment of dams with apocynin prevented this increase in brain damage following ischemia/reperfusion. CONCLUSIONS: We suggest that our findings may have important implications for the pathogenesis of brain abnormalities associated with fetal alcohol exposure.
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Arteriolas/fisiopatología , Encéfalo/patología , Encéfalo/fisiopatología , Etanol/efectos adversos , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Daño por Reperfusión/patología , Acetofenonas/farmacología , Adenosina Difosfato/farmacología , Animales , Encéfalo/irrigación sanguínea , Inhibidores Enzimáticos/farmacología , Etanol/antagonistas & inhibidores , Agonistas de Aminoácidos Excitadores/farmacología , Femenino , Infarto/patología , Infarto de la Arteria Cerebral Media/patología , Masculino , N-Metilaspartato/farmacología , Nitroglicerina/farmacología , Embarazo , Ratas , Daño por Reperfusión/prevención & control , omega-N-Metilarginina/farmacologíaRESUMEN
We investigated the effect of experimental preeclampsia on hyperemia during seizure in the hippocampus and vascular function and structure of hippocampal arterioles using Sprague Dawley rats (n = 14/group) that were nonpregnant, pregnant (d20), or had experimental preeclampsia (induced by a high cholesterol diet d7-20). Hyperemia was measured via hydrogen clearance basally and during pentylenetetrazol-induced seizure (40-130 mg/kg i.v.). Reactivity of isolated and pressurized hippocampal arterioles to KCl, nitric oxide synthase inhibition with NG-nitro-L-arginine methyl ester and the nitric oxide donor sodium nitroprusside were investigated. Capillary density was quantified via immunohistochemistry. Cerebral blood flow increased during seizure vs. baseline in pregnant (118 ± 14 vs. 87 ± 9 mL/100 g/min; p < 0.05) and nonpregnant rats (106 ± 9 vs. 82 ± 9 mL/100 g/min; p < 0.05) but was unchanged in preeclamptic rats (79 ± 16 vs. 91 ± 4 mL/100 g/min; p > 0.05), suggesting impaired seizure-induced hyperemia in preeclampsia. Hippocampal arterioles from preeclamptic rats had less basal tone, and dilated less to 15 mM KCl (9 ± 8%) vs. pregnant (61 ± 27%) and nonpregnant rats (20 ± 11%). L-NAME had no effect on hippocampal arterioles in any group, but dilation to sodium nitroprusside was similar. Structurally, hippocampal arterioles from preeclamptic rats underwent inward hypotrophic remodeling and capillary rarefaction. Impaired seizure-induced hyperemia, vascular dysfunction, and limited vasodilatory reserve of hippocampal arterioles could potentiate hippocampal injury in preeclampsia especially during eclampsia.
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Arteriolas/patología , Región CA3 Hipocampal/irrigación sanguínea , Circulación Cerebrovascular/fisiología , Hiperemia/patología , Preeclampsia/patología , Convulsiones/patología , Animales , Arteriolas/fisiopatología , Región CA3 Hipocampal/fisiopatología , Femenino , Hiperemia/complicaciones , Hiperemia/fisiopatología , Preeclampsia/fisiopatología , Embarazo , Ratas Sprague-Dawley , Convulsiones/complicaciones , Convulsiones/fisiopatologíaRESUMEN
Our previous findings indicated that in rats subjected to subarachnoid hemorrhage (SAH), suppression of post-SAH neuroinflammation via vascular adhesion protein-1 (VAP-1) blockade provides significant neuroprotection. We and others have reported that neuroinflammation contributes to cerebral microvascular impairment. Thus, in the present study, we tested the hypotheses that: (1) treatment with LJP-1586, a selective VAP-1 blocker, prevents SAH-associated pial arteriolar dilating dysfunction; and (2) the vasculoprotective effect of LJP-1586 arises from inhibiting SAH-elicited neutrophil recruitment. We utilized an endovascular perforation model of SAH. Rats subjected to SAH were either treated with LJP-1586 or rendered neutropenic via anti-neutrophil-antibody treatment. Findings from these groups were compared to their respective control groups. At 48 h post-SAH, rats were evaluated for neurobehavioral function, pial venular leukocyte trafficking, and pial arteriolar reactivity to topically-applied acetylcholine (ACh) and S-nitroso-N-acetyl penicillamine (SNAP). Pial arteriolar responses decreased at 48 h post-SAH. However, in the presence of LJP-1586, those responses were significantly preserved. Neutrophil-depletion yielded a substantial suppression of SAH-associated leukocyte adhesion and infiltration. This was accompanied by a significant preservation of pial arteriolar dilating function, suggesting a direct link between neutrophil recruitment and the loss of cerebral microvascular reactivity. Moreover, neutrophil depletion also was associated with significant protection of neurobehavioral function. The present findings suggest that attenuating SAH-linked elevation in neutrophil trafficking will protect against the development of microvascular dysfunction and subsequent neurological impairment.
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Alilamina/análogos & derivados , Amina Oxidasa (conteniendo Cobre)/antagonistas & inhibidores , Fármacos Cardiovasculares/farmacología , Moléculas de Adhesión Celular/antagonistas & inhibidores , Infiltración Neutrófila/efectos de los fármacos , Hemorragia Subaracnoidea/tratamiento farmacológico , Acetilcolina/farmacología , Alilamina/farmacología , Amina Oxidasa (conteniendo Cobre)/metabolismo , Animales , Arteriolas/efectos de los fármacos , Arteriolas/fisiopatología , Moléculas de Adhesión Celular/metabolismo , Circulación Cerebrovascular/efectos de los fármacos , Circulación Cerebrovascular/fisiología , Agonistas Colinérgicos/farmacología , Modelos Animales de Enfermedad , Leucocitos/efectos de los fármacos , Leucocitos/fisiología , Masculino , Neuroinmunomodulación/efectos de los fármacos , Neuroinmunomodulación/fisiología , Infiltración Neutrófila/fisiología , Neutrófilos/efectos de los fármacos , Neutrófilos/fisiología , Donantes de Óxido Nítrico/farmacología , Piamadre/irrigación sanguínea , Piamadre/efectos de los fármacos , Piamadre/fisiopatología , Ratas Sprague-Dawley , Flujo Sanguíneo Regional/efectos de los fármacos , Flujo Sanguíneo Regional/fisiología , S-Nitroso-N-Acetilpenicilamina/farmacología , Hemorragia Subaracnoidea/mortalidad , Hemorragia Subaracnoidea/fisiopatología , Vénulas/efectos de los fármacos , Vénulas/fisiopatologíaRESUMEN
Objective Toobservetheclinicalsignificanceofcerebrovascularhemodynamicindex (CVHI)inthepatientswithsilentcerebralinfarction.Methods Atotalof180patientsperformed cerebrovascular hemodynamics with ultrasound and head MRI examinations were enrolled retrospectively. They were divided into three groups:60 patients with silent cerebral infraction (SCI)were used as a SCI group,60 age-,sex- and previous medical history-matched high risk patients with cerebrovascular disease were used as a cerebrovascular disease risk factor (CV-HRF)group,and 60 healthy subjects were used as a normal control group over the same period. Cerebrovascular function detector was used to collect CVHI at the bilateral carotid arteries. The CVHI features of the 3 groups were analyzed and compared. Results Comparedwiththecontrolgroup,thereweresignificantchangesinvariousindexesofcerebral vascular hemodynamics in the SCI group and the CV-HRF group. The indexes of reflecting the cerebral blood supply state included significantly decreased mean blood flow,mean flow velocity,maximum flow velocity,and minimum flow velocity (P<0. 05);the indexes reflecting vascular elastic properties and resistance status included the increased pulse wave velocity,characteristic impedance,peripheral resistance,and dynamic resistance (P<0. 05);the indexes reflecting cerebral microcirculation included significantly increased critical pressure and decreased differential pressure (P<0. 05);the total score of cerebrovascular function was also decreased significantly,they were 44 ± 9,51 ± 5,and 85 ± 7,respectively (P<0. 05);there were significance differences in the distribution of total score amongthe3groups(P<0.05).Conclusion Thehigh-riskpatientswithsilentcerebralinfarction and cerebrovascular disease have the CVHI changes. The total integrated value of cerebrovascular function declined,and the former is more obvious.