Abstract
The coronary microcirculation plays a pivotal role in the regulation of coronary blood flow and cardiac metabolism. It can adapt to acute and chronic pathologic conditions such as coronary ...thrombosis or long-standing hypertension. Due to the fact that the coronary microcirculation cannot be visualized in human beings in vivo, its assessment remains challenging. Thus, the clinical importance of the coronary microcirculation is still often underestimated or even neglected. Depending on the clinical condition of the respective patient, several non-invasive (e.g. transthoracic Doppler-echocardiography assessing coronary flow velocity reserve, cardiac magnetic resonance imaging, positron emission tomography) and invasive methods (e.g. assessment of coronary flow reserve (CFR) and microvascular resistance (MVR) using adenosine, microvascular coronary spasm with acetylcholine) have been established for the assessment of coronary microvascular function. Individual patient characteristics, but certainly also local availability, methodical expertise and costs will influence which methods are being used for the diagnostic work-up (non-invasive and/or invasive assessment) in a patient with recurrent symptoms and suspected coronary microvascular dysfunction. Recently, the combined invasive assessment of coronary vasoconstrictor as well as vasodilator abnormalities has been titled interventional diagnostic procedure (IDP). It involves intracoronary acetylcholine testing for the detection of coronary spasm as well as CFR and MVR assessment in response to adenosine using a dedicated wire. Currently, the IDP represents the most comprehensive coronary vasomotor assessment. Studies using the IDP to better characterize the endotypes observed will hopefully facilitate development of tailored and effective treatments.
Key points
The results of the present study establish the temporal pattern of age‐related vascular dysfunction across the adult lifespan in sedentary mice consuming a non‐Western diet, and the ...underlying mechanisms
The results demonstrate that consuming a Western diet accelerates and exacerbates vascular ageing across the lifespan in sedentary mice
They also show that lifelong voluntary aerobic exercise has remarkable protective effects on vascular function throughout the lifespan, in the setting of ageing alone, as well as ageing compounded by Western diet consumption
Overall, the results indicate that amelioration of mitochondrial oxidative stress and inflammation are key mechanisms underlying the voluntary aerobic exercise‐associated preservation of vascular function across the lifespan in both the presence and absence of a Western dietary pattern
Advancing age is the major risk factor for cardiovascular diseases, driven largely by vascular endothelial dysfunction (impaired endothelium‐dependent dilatation, EDD) and aortic stiffening (increased aortic pulse wave velocity, aPWV). In humans, vascular ageing occurs in the presence of differences in diet and physical activity, but the interactive effects of these factors are unknown. We assessed carotid artery EDD and aPWV across the lifespan in mice consuming standard (normal) low‐fat chow (NC) or a high‐fat/high‐sucrose Western diet (WD) in the absence (sedentary, SED) or presence (voluntary wheel running, VWR) of aerobic exercise. Ageing impaired nitric oxide‐mediated EDD (peak EDD 88 ± 12% 6 months P = 0.003 vs. 59 ± 9% 27 months NC‐SED), which was accelerated by WD (60 ± 18% 6 months WD‐SED). In NC mice, aPWV increased 32% with age (423 ± 13 cm/s at 24 months P < 0.001 vs. 321 ± 12 cm/s at 6 months) and absolute values were an additional ∼10% higher at any age in WD mice (P = 0.042 vs. NC‐SED). Increases in aPWV with age in NC and WD mice were associated with 30–65% increases in aortic intrinsic wall stiffness (6 vs. 19–27 months, P = 0.007). Lifelong aerobic exercise prevented age‐ and WD‐related vascular dysfunction across the lifespan, and this protection appeared to be mediated by mitigation of vascular mitochondrial oxidative stress and inflammation. Our results depict the temporal impairment of vascular function over the lifespan in mice, acceleration and exacerbation of that dysfunction with WD consumption, the remarkable protective effects of voluntary aerobic exercise, and the underlying mechanisms.
Key points
The results of the present study establish the temporal pattern of age‐related vascular dysfunction across the adult lifespan in sedentary mice consuming a non‐Western diet, and the underlying mechanisms
The results demonstrate that consuming a Western diet accelerates and exacerbates vascular ageing across the lifespan in sedentary mice
They also show that lifelong voluntary aerobic exercise has remarkable protective effects on vascular function throughout the lifespan, in the setting of ageing alone, as well as ageing compounded by Western diet consumption
Overall, the results indicate that amelioration of mitochondrial oxidative stress and inflammation are key mechanisms underlying the voluntary aerobic exercise‐associated preservation of vascular function across the lifespan in both the presence and absence of a Western dietary pattern
Objective
To study endothelial dysfunction in patients with psoriatic arthritis (PsA) without risk factors for cardiovascular disease.
Methods
Forty patients with PsA according to Classification ...Criteria for Psoriatic Arthritis (CASPAR) criteria and forty age‐ and sex‐matched controls were included. Patients with risk factors for cardiovascular disease were excluded. Endothelial function was assessed by measuring endothelial‐dependent flow‐mediated vasodilatation (FMD%) and endothelial‐independent nitroglycerin‐mediated dilatation (NMD%) in the brachial artery.
Results
There was a significant impairment of FMD% in patients as compared to controls (mean 8.3% vs. 10.8%, P = 0.007), but there was no significant difference in NMD%.
Conclusions
There is presence of endothelial dysfunction in patients with PsA independent of risk factors for cardiovascular disease.
New Findings
What is the central question of this study?
It remains to be determined whether type 2 diabetes attenuates muscarinic and nicotinic cutaneous vasodilatation and sweating as well as ...purinergic cutaneous vasodilatation.
What is the main finding and its importance?
We show that type 2 diabetes specifically attenuates purinergic cutaneous vasodilatation without influencing muscarinic and nicotinic cutaneous vasodilatation and sweating. Our results provide valuable new information regarding the receptor‐specific influence of type 2 diabetes on microvascular and sudomotor function.
The present study evaluated whether type 2 diabetes (T2D) attenuates muscarinic and/or nicotinic cutaneous vasodilatation and sweating as well as purinergic cutaneous vasodilatation. Cutaneous vascular conductance and sweat rate were evaluated in 12 healthy non‐diabetic older adults (Control, 60 ± 8 years) and 13 older adults with T2D (62 ± 10 years) at three intradermal forearm skin sites perfused with the following: (i) methacholine (muscarinic receptor agonist, five doses: 0.0125, 0.25, 5, 100 and 2000 mm); (ii) nicotine (nicotinic receptor agonist, five doses: 1.2, 3.6, 11, 33 and 100 mm); or (iii) ATP (purinergic receptor agonist, five doses: 0.03, 0.3, 3, 30 and 300 mm). Each agonist was administered for 25 min per dose. At the end of the protocol, 50 mm sodium nitroprusside was administered to all skin sites to elicit maximal cutaneous vasodilatation. Cutaneous vascular conductance during methacholine and nicotine administration did not differ between groups (all P > 0.05). In contrast, cutaneous vascular conductance during administration of 30 mm (42 ± 28 versus 63 ± 26% maximum, P ≤ 0.05) and 300 mm ATP (56 ± 24 versus 71 ± 20% maximum, P ≤ 0.05) was attenuated in individuals with T2D in comparison to the Control participants. Furthermore, cutaneous vascular conductance during administration of 50 mm sodium nitroprusside was lower in individuals with T2D relative to Control subjects (P = 0.04). Methacholine‐ and nicotine‐induced sweating was similar between groups (all P > 0.05). Thus, T2D attenuates purinergic cutaneous vasodilatation without affecting muscarinic and nicotinic cutaneous vascular and sweating responses.
Diastolic shock index (DSI) is a new measurement of vasodilatation which can be used to identify a poor prognosis in septic shock.(1) DSI is dividing the heart rate by the diastolic pressure. If over ...2.2 it indicates vasodilation in septic shock. This measurement has not been validated for therapeutic intervention in septic shock.(1) These measurements are always available during cardiac surgery. The assessment of vasodilatation and the haemodynamic management can be made by measuring the ventricular-arterial coupling ratio with transesophageal echo. The measurements with transesophageal echo needs expertise and a simpler continuous measurement such as the diastolic shock index would be advantageous. This study compares the correlation between the two methods, and its validity in cardiac surgery.
All patients presenting for cardiac surgery and being anaesthetised by the author were recruited. The patients were anaesthetised and monitored according to established practice. If and when the mean arterial pressure fell below 65 mmHg during the procedure, the coupling ratio and the diastolic shock index were measured. Analysis was done to compare whether the diastolic shock index was comparable to the information available from the ventricular -arterial coupling ratio.
25 measurements were taken when the MAP was less than 65 in a series of patients.
With the MAP less than 65 the DSI was over 2.2 in only 2 patients.(8%)
The coupling ratio showed vasodilatation in 64% and decoupling in 20%. There were 84% abnormal ventricular coupling ratios. There were also 40% who showed fluid deficit and fluid responsiveness.36% showed both low coupling ratio and fluid deficit and responsiveness. 4% showed only fluid deficit and responsiveness. The patients were managed according to the information obtained from the ventricular-arterial coupling ratio with fluids, vasopressors and inotropes. There was good response and no mortality.
There is no relationship between the coupling ratio and the DSI. The DSI cannot be used to identify the cause of low blood pressure in patients under going cardiac surgery and also cannot be used to guide therapy in the presence of low blood pressure during cardiac surgery.
1. Ospina-Tascon G A, Teboul JL, Hernandez G et al. Diastolic shock index and clinical outcomes in patients with septic shock. Ann. Intensive Care 2020. 10, 41
Quercetin has attracted more attention in recent years due to its protective role against ischemia/reperfusion injury. Quercetin can alleviate oxidative stress injury through the inhibition of NADPH ...oxidase and xanthine oxidase, blockage of the Fenton reaction, and scavenging of reactive oxygen species. Quercetin can also exert anti-inflammatory and anti-apoptotic effects by reducing the response to inflammatory factors and inhibiting cell apoptosis. Moreover, it can induce vasodilation effects through the inhibition of endothelin-1 receptors, the enhancement of NO stimulation and the activation of the large-conductance calcium-activated potassium channels. Finally, Quercetin can also antagonize the calcium overload. These multifaceted activities of Quercetin make it a potential therapeutic alternative for the treatment of ischemia/reperfusion injury.
Nebivolol, a selective
β
‐adrenoceptor (
β
1
‐AR) antagonist, induces vasodilatation by an endothelium‐ and NO‐cGMP‐dependent pathway. However, the mechanisms involved in the vascular effect of ...nebivolol have not been established. Thus, we evaluated the role of
α
1
and
β
3
‐ARs in nebivolol‐induced vasodilatation.
The responses to nebivolol were investigated
in vitro
in thoracic aortic rings isolated from male Sprague–Dawley rats.
Nebivolol (0.1–10
μ
M
) significantly shifted the concentration–response curve to phenylephrine, an
α
1
‐AR agonist, to the right in a concentration‐dependent manner (p
A
2
=6.5). Conversely, the concentration–response curve to endothelin 1 (ET1) was unaffected by nebivolol.
In ET1‐precontracted rings, nebivolol induced a concentration‐dependent relaxation, which was unaffected by nadolol (a
β
1
/
β
2
‐AR antagonist) but was significantly reduced by L‐748,337 (a
β
3
‐AR antagonist), endothelium removal or pretreatment with L‐NMMA (an NOS inhibitor). Similar results were obtained with a
β
3
‐AR agonist, SR 58611A.
It was concluded that, in rat aorta, nebivolol‐induced relaxation results from both inhibition of
α
1
‐ARs and activation of
β
3
‐ARs. In addition, we confirmed that the endothelium and the NO pathway are involved in the vascular effect of nebivolol. The identification of these vascular targets of nebivolol indicate that it has therapeutic potential for the treatment of pathological conditions associated with an elevation of sympathetic tone, such as heart failure and hypertension.
British Journal of Pharmacology
(2006)
147
, 699–706. doi:
10.1038/sj.bjp.0706648
Obesity dramatically increases the risk of development of cardiovascular and metabolic diseases. Endothelial dysfunction induced by obesity is an important risk factor that impairs blood flow ...controls in various organs. Impaired endothelial function occurs early in life in obese children. Obesity‐induced endothelial dysfunction is associated with decreased nitric oxide (NO) production due to impaired endothelial NO synthase activity and expression and increased production of superoxide anion and the endogenous NOS inhibitor ADMA, together with increased vasoconstrictor factors, such as endothelin‐1 and sympathetic nerve activation. Decreased endothelial progenitor cells are also involved in endothelial cell senescence in obese individuals. Insulin resistance and diabetes mellitus augment obesity‐induced endothelial dysfunction. Adipokines liberated from adipose tissues play roles in modulating endothelial function; adiponectin and ghrelin have beneficial effects on endothelial cells. Effects of leptin on endothelial function are controversial. Decreased body weight by physical exercise, dietary interventions, and bariatric surgery are effective measures that reverse endothelial dysfunction; however, the weight control is not only the reason for improving of endothelia function. Pharmacological therapies with β‐adrenoceptor antagonists, resveratolol, anti‐obesity agents, nifedipine, and NADPH oxidase inhibitors may also be effective; however, these treatments have to be utilized under the basis of exercise and dietary controls.
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