Vasodilation

Arginase 2 (Arg2) is a critical target in atherosclerosis because it controls endothelial nitric oxide, proliferation, fibrosis, and inflammation. Regulators of Arg2 transcription in the endothelium have not been characterized. The goal of the current study is to determine the role of specific histone deacetylases (HDACs) in the regulation of endothelial Arg2 transcription and endothelial function. The HDAC inhibitor trichostatin A increased levels of Arg2 mRNA, protein, and activity in both human aortic endothelial cells and mouse aortic rings. These changes occurred in both time- and dose-dependent patterns and resulted in Arg2-dependent endothelial dysfunction. Trichostatin A and the atherogenic stimulus oxidized low-density lipoprotein enhanced the activity of common promoter regions of Arg2. HDAC inhibition with trichostatin A also decreased endothelial nitric oxide, and these effects were blunted by arginase inhibition. Nonselective class I HDAC inhibitors enhanced Arg2 expres...

The tight coupling between neuronal activity and the local increase of blood flow termed neurovascular coupling is essential for normal brain function. This mechanism of regulation is compromised in Alzheimer’s Disease (AD). In order to determine whether a purely vascular dysfunction or a neuronal alteration of blood vessels diameter control could be responsible for the impaired neurovascular coupling observed in AD, blood vessels reactivity in response to different pharmacological stimulations was examined in double transgenic APPxPS1 mice model of AD. Blood vessels movements were monitored using infrared videomicroscopy ex vivo, in cortical slices of 8 month-old APPxPS1 and wild type (WT) mice. We quantified vasomotor responses induced either by direct blood vessel stimulation with a thromboxane A2 analogue, the U46619 (9,11-dideoxy-11a,9a-epoxymethanoprostaglandin F2α) or via the stimulation of interneurons with the nicotinic acetylcholine receptor (nAChRs) agonist DMPP (1,1-Dime...

Myocardial perfusion and regional wall motion during adenosine-induced coronary vasodilation were assessed in 40 patients with angina pectoris by technetium-99m sestamibi single-photon emission computed tomography (SPECT) and simultaneous 2-dimensional echocardiography. Adenosine was infused intravenously at a dose of 140 micrograms/kg body weight per minute for 6 minutes, and technetium-99m sestamibi was injected at 3 minutes. Adenosine caused a significant decrease in systolic and diastolic blood pressure and a significant increase in heart rate and the heart rate-blood pressure product. Adverse effects were mild and transient and no patient required aminophylline. Completely or partially reversible defects on SPECT were present in 28 patients, a fixed defect was seen in 4 patients, and no defect was seen in 8 patients. Two-dimensional echocardiography revealed a new or worsening wall motion abnormality in 21 patients, a fixed abnormality in 4 patients and no abnormality in 15. Transient perfusion defects were associated with transient wall motion abnormalities in 71% of cases. The overall sensitivity, specificity and predictive accuracy of adenosine echocardiography in detecting significant coronary artery disease (> 50% diameter stenosis) were 74, 100 and 78%, respectively, whereas those of adenosine SPECT were 94, 100 and 95%, respectively (p < 0.05, NS, and < 0.05, respectively). Thus adenosine technetium-99m sestamibi SPECT has a higher sensitivity and predictive accuracy than adenosine echocardiography, suggesting that adenosine-induced perfusion defects are not always associated with wall motion abnormality.(ABSTRACT TRUNCATED AT 250 WORDS)

... Structure and the resistance amplifier in hypertension: reply to the dissenters. Korner, Paul I. 1 ; Angus, James A. 1,2 ; Wright, Christine E. 1. Article Outline. Collapse Box Author Information. ... The Korner-Angus model. Izzard et al. ...

Syncope is a sudden transient loss of consciousness and postural tone caused by cerebral hypoperfusion. The most common form is vasovagal syncope (VVS). Presyncopal progressive early hypotension in older VVS patients is caused by reduced cardiac output (CO); younger patients have reduced systemic vascular resistance (SVR). Using a priori criteria for reduced CO (↓CO) and SVR (↓SVR), we studied 48 recurrent young fainters comparing subgroups of VVS with VVS-↓CO, VVS-↓SVR, and both VVS-↓CO&↓SVR. Subjects were studied supine and during 70-degrere upright tilt with a Finometer to continuously measure blood pressure, CO, and SVR and impedance plethysmography to estimate thoracic, splanchnic, pelvic, and calf blood volumes, blood flows, and vascular resistances and electrocardiogram to measure heart rate and rhythm. Central blood volume was decreased in all VVS compared to control. VVS-↓CO was associated with decreased splanchnic blood flow and increased splanchnic blood pooling compared ...

After the pandemic COVID-19, the severe patient has persistent symptoms for a long period
without a definitive disease is called post COVID-19 syndrome. It affected 10% of affected
COVID-19 patients after discharge from the hospital. The relation between ACE2 protein
deficiency and COVID-19 is more concerned in this article as covid-19 enters the host through
ACE2. The ACE2 level and angiotensin (1-7) levels affect the symptoms in post-COVID -19. The
function of angiotensin (1-7) is required to know the relation between angiotensin (1-7) and
COVID-19. Pulmonary rehabilitation affects the COVID-19 symptoms which persist after
discharge from the hospital. The researcher reviewed more scientific-based articles to know the
most persistent symptoms after post-COVID-19, organ involvement, the association of ACE2
deficiency in COVID-19, Ang (1-7) function in our body, the pulmonary rehabilitation benefits in
post-COVID -19 syndrome. The elder people will most have multiorgan involvement in the aging
process. When they will be affected with COVID-19. It will enhance their symptoms to severe
forms. The improvement of quality of life in elder patients is possible through pursed lip breathing,
diaphragm breathing, slow breathing exercise correctly with proper guidance in the pulmonary
rehabilitation center.

Rationale: According to general view, aldehyde dehydrogenase-2 (ALDH2) catalyzes the high-affinity pathway of vascular nitroglycerin (GTN) bioactivation in smooth muscle mitochondria. Despite having wide implications to GTN pharmacology and raising many questions that are still unresolved, mitochondrial bioactivation of GTN in blood vessels is still lacking experimental support. Objective: In the present study, we investigated whether bioactivation of GTN is affected by the subcellular localization of ALDH2 using immortalized ALDH2-deficient aortic smooth muscle cells and mouse aortas with selective overexpression of the enzyme in either cytosol or mitochondria. Methods and Results: Quantitative Western blotting revealed that ALDH2 is mainly cytosolic in mouse aorta and human coronary arteries, with only approximately 15% (mouse) and approximately 5% (human) of the enzyme being localized in mitochondria. Infection of ALDH2-deficient aortic smooth muscle cells or isolated aortas with...

OBJECTIVES: The purpose of this study was to develop an adenosine-independent, pressure-derived index of coronary stenosis severity. BACKGROUND: Assessment of stenosis severity with fractional flow reserve (FFR) requires that coronary resistance is stable and minimized. This is usually achieved by administration of pharmacological agents such as adenosine. In this 2-part study, we determine whether there is a time when resistance is naturally minimized at rest and assess the diagnostic efficiency, compared with FFR, of a new pressure-derived adenosine-free index of stenosis severity over that time. METHODS: A total of 157 stenoses were assessed. In part 1 (39 stenoses), intracoronary pressure and flow velocity were measured distal to the stenosis; in part 2 (118 stenoses), intracoronary pressure alone was measured. Measurements were made at baseline and under pharmacologic vasodilation with adenosine. RESULTS: Wave-intensity analysis identified a wave-free period in which intracoron...

Hypertension is associated with cerebrovascular remodeling and endothelial dysfunction, which may reduce cerebral vasomotor reactivity to CO2. Treatment combining blood pressure (BP) reduction with inhibition of vascular effects of angiotensin II may reverse these changes. However, the reduction in BP at the onset of treatment can compromise cerebral perfusion and exhaust vasomotor reserve, leading to impaired CO2 reactivity. Eleven patients (nine men, two women) with newly diagnosed, untreated mild-to-moderate hypertension aged (mean (s.d.)) 52 (9) years, and eight controls (seven men, one woman) aged 46 (10) years were studied. Patients received losartan/hydrochlorothiazide (50/12.5 or 100/25 mg) to reduce BP to <140/<90 mm Hg within 1-2 weeks. BP (Finapres), heart rate (HR), CBFV (cerebral blood flow velocity, transcranial Doppler), cerebrovascular resistance, and CO2 reactivity were measured at baseline, after the rapid BP reduction, and after long-term treatment (3-4 mont...

Background: The pulse oximeter perfusion index (PI) has been used to indicate sympathectomy-induced vasodilatation. We hypothesized that pulse oximeter PI provides an earlier and clearer indication of sympathectomy following epidural anesthesia than skin temperature and arterial pressure.Methods: Forty patients received lumbar epidural catheters. Patients were randomized to receive either 10 ml 0.5% bupivacaine or 10 ml 0.25% bupivacaine. PI in the toe, mean arterial pressure (MAP) and toe temperature were all assessed at baseline and at 5, 10 and 20 min following epidural anesthesia. The effect of epidural anesthesia over time was assessed by repeated measures analysis of variance. Additionally, we defined clinically evident sympathectomy criteria (a 100% increase in the PI, a 15% decrease in MAP and a 1 °C increase in toe temperature). The numbers of patients demonstrating these changes for each test were compared using the McNemar test for each time point.Results: Twenty-nine subjects had photoplethysmography signals that met a priori signal quality criteria for analysis. By 20 min, PI increased by 326%, compared with a 10% decrease and a 3% increase in MAP and toe temperature, respectively. For PI 15/29, 26/29 and 29/29 of the subjects met the sympathectomy criteria at 5, 10 and 20 min, respectively, compared with 4/29, 6/29 and 18/29 for MAP changes and 3/29, 8/29 and 14/29 for toe temperature changes.Conclusions: PI was an earlier, clearer and more sensitive indicator of the development of epidural-induced sympathectomy than either skin temperature or MAP.