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Journal of Cerebral Blood Flow and... Jan 2018Aneurysmal subarachnoid hemorrhage (SAH) is a devastating cerebral event that kills or debilitates the majority of those afflicted. The blood that spills into the... (Review)
Review
Aneurysmal subarachnoid hemorrhage (SAH) is a devastating cerebral event that kills or debilitates the majority of those afflicted. The blood that spills into the subarachnoid space stimulates profound cerebral artery vasoconstriction and consequently, cerebral ischemia. Thus, once the initial bleeding in SAH is appropriately managed, the clinical focus shifts to maintaining/improving cerebral perfusion. However, current therapeutic interventions largely fail to improve clinical outcome, because they do not effectively restore normal cerebral artery function. This review discusses emerging evidence that perturbed cerebrovascular "myogenic reactivity," a crucial microvascular process that potently dictates cerebral perfusion, is the critical element underlying cerebral ischemia in SAH. In fact, the myogenic mechanism could be the reason why many therapeutic interventions, including "Triple H" therapy, fail to deliver benefit to patients. Understanding the molecular basis for myogenic reactivity changes in SAH holds the key to develop more effective therapeutic interventions; indeed, promising recent advancements fuel optimism that vascular dysfunction in SAH can be corrected to improve outcome.
Topics: Cerebral Arteries; Cerebrovascular Circulation; Humans; Muscle, Smooth, Vascular; Subarachnoid Hemorrhage; Vasoconstriction
PubMed: 29135346
DOI: 10.1177/0271678X17742548 -
Kidney & Blood Pressure Research 2016Intradialytic hypertension (IH) occurs frequently in some hemodialysis patients and increases mortality risk. We simultaneously compared pre-dialysis, post-dialysis and...
BACKGROUND/AIMS
Intradialytic hypertension (IH) occurs frequently in some hemodialysis patients and increases mortality risk. We simultaneously compared pre-dialysis, post-dialysis and changes in extracellular volume and hemodynamics in recurrent IH patients and controls.
METHODS
We performed a case-control study among prevalent hemodialysis patients with recurrent IH and hypertensive hemodialysis controls. We used bioimpedance spectroscopy and impedance cardiography to compare pre-dialysis, post-dialysis, and intradialytic change in total body water (TBW) and extracellular water (ECW), as well as cardiac index (CI) and total peripheral resistance index (TPRI).
RESULTS
The ECW/TBW was 0.453 (0.05) pre-dialysis and 0.427 (0.04) post-dialysis in controls vs. 0.478 (0.03) and 0.461 (0.03) in IH patients (p=0.01 post-dialysis). The ECW/TBW change was -0.027 (0.03) in controls and -0.013 (0.02) in IH patients (p=0.1). In controls, pre- and post-dialysis TPRI were 3254 (994) and 2469 (529) dynes/sec/cm2/m2 vs. 2983 (747) and 3408 (980) dynes/sec/cm2/m2 in IH patients (p=0.002 post-dialysis). There were between-group differences in TPRI change (0=0.0001), but not CI (p=0.09).
CONCLUSIONS
Recurrent intradialytic hypertension is associated with higher post-dialysis extracellular volume and TPRI. Intradialytic TPRI surges account for the vasoconstrictive state post-dialysis, but intradialytic fluid shifts may contribute to post-hemodialysis volume expansion.
Topics: Adult; Body Water; Case-Control Studies; Electric Impedance; Extracellular Fluid; Female; Fluid Shifts; Humans; Hypertension; Male; Middle Aged; Recurrence; Renal Dialysis; Vasoconstriction
PubMed: 27832647
DOI: 10.1159/000450565 -
Experimental Physiology Dec 2015What is the topic of this review? This review considers how local dilator mechanisms and increased sympathetic nerve activity interact during acute systemic hypoxia and... (Review)
Review
What is the topic of this review? This review considers how local dilator mechanisms and increased sympathetic nerve activity interact during acute systemic hypoxia and then reviews current understanding of some of the modifications induced by chronic hypoxia. What advances does it highlight? During acute hypoxia, local levels of hypoxia determine the release of vasodilators and magnitude of arteriolar dilatation, as well as the extent to which sympathetically evoked vasoconstriction is blunted, so maximizing distribution of O2 to muscle fibres. Chronic hypoxia in adult life and fetal programming induced by chronic hypoxia in utero lead to increased responsiveness to acute hypoxia and further blunting of sympathetic vasoconstriction, but are also associated with hypertension. In resting skeletal muscle, acute systemic hypoxia evokes vasodilatation, while vasoconstriction evoked by increased muscle sympathetic nerve activity is blunted, referred to herein as hypoxic sympatholysis. This review considers the contributions of adenosine, prostaglandin I2 , nitric oxide, ATP and endothelium-derived hyperpolarizing factors to the muscle vasodilatation, with particular attention being given to the release and actions of adenosine, which plays a dominant role. It is argued that the dilator substances are released in proportion to the local level of hypoxia, notably, allowing terminal arterioles to regulate O2 distribution through the capillaries. Correspondingly, hypoxic sympatholysis can be attributed to the ability of local hypoxia to blunt vasoconstriction evoked by noradrenaline acting on α1 - and α2 -adrenoceptors. The synergistic actions of ATP as cotransmitter may be depressed in parallel, but the actions of neuropeptide Y persist. Consideration is also given to the changes induced by chronic hypoxia in adult life and to the consequences in adult life of fetal programming induced by chronic hypoxia during pregnancy. In both conditions, dilator responsiveness to acute hypoxia is maintained, but the action or release of adenosine is altered in ways that are not yet understood. Both conditions are also accompanied by blunted sympathetically evoked vasoconstriction, tonically raised muscle sympathetic nerve activity, and increased muscular vascular tone and arterial blood pressure. With hypoxia-induced fetal programming, arterial pressure is increased in young adults and increases with age. The mechanisms underlying these changes are discussed, and it is argued that chronic hypoxia in adult life or in utero may facilitate development of hypertension.
Topics: Animals; Humans; Hypoxia; Muscle, Skeletal; Sympathetic Nervous System; Vasoconstriction; Vasoconstrictor Agents; Vasodilation; Vasodilator Agents
PubMed: 26263443
DOI: 10.1113/EP085139 -
American Journal of Physiology. Heart... Oct 2020Patients with type 2 diabetes mellitus (T2DM) exhibit diminished exercise capacity likely attributable to reduced skeletal muscle blood flow (i.e., exercise hyperemia)....
Patients with type 2 diabetes mellitus (T2DM) exhibit diminished exercise capacity likely attributable to reduced skeletal muscle blood flow (i.e., exercise hyperemia). A potential underlying mechanism of the impaired hyperemic response to exercise could be inadequate blunting of sympathetic-mediated vasoconstriction (i.e., poor functional sympatholysis). Therefore, we studied the hyperemic and vasodilatory responses to handgrip exercise in patients with T2DM as well as vasoconstriction to selective α-agonist infusion. Forearm blood flow (FBF) and vascular conductance (FVC) were examined in patients with T2DM ( = 30) as well as nondiabetic controls ( = 15) with similar age (59 ± 9 vs. 60 ± 9 yr, = 0.69) and body mass index (31.4 ± 5.2 vs. 29.5 ± 4.6 kg/m, = 0.48). Intra-arterial infusion of phenylephrine (α-agonist) and dexmedetomidine (α-agonist) were used to induce vasoconstriction: [(FVC - FVC)/FVC × 100%]. Subjects completed rest and dynamic handgrip exercise (20% of maximum) trials per α-agonist. Patients with T2DM had smaller increases (Δ from rest) in FBF (147 ± 71 vs. 199 ± 63 ml/min) and FVC (126 ± 58 vs. 176 ± 50 ml·min·100 mmHg, < 0.01 for both) during exercise compared with controls, respectively. During exercise, patients with T2DM had greater α- (-16.9 ± 5.9 vs. -11.3 ± 3.8%) and α-mediated vasoconstriction (-23.5 ± 7.1 vs. -19.0 ± 6.5%, < 0.05 for both) versus controls. The magnitude of sympatholysis (Δ in %vasoconstriction between exercise and rest) for PE was lower (worse) in patients with T2DM versus controls (14.9 ± 12.2 vs. 23.1 ± 8.1%, < 0.05) whereas groups were similar during DEX trials (24.6 ± 12.3 vs. 27.6 ± 13.4%, = 0.47). Our data suggest patients with T2DM have attenuated hyperemic and vasodilatory responses to exercise, which could be attributable to greater α-mediated vasoconstriction in contracting skeletal muscle. Findings presented in this article are the first to show patients with type 2 diabetes mellitus have blunted hyperemic and vasodilatory responses to dynamic handgrip exercise. Moreover, we illustrate greater α-adrenergic-mediated vasoconstriction may contribute to our initial observations. Collectively, these data suggest patients with type 2 diabetes may have impaired functional sympatholysis, which can contribute to their reduced exercise capacity.
Topics: Adrenergic alpha-1 Receptor Agonists; Aged; Diabetes Mellitus, Type 2; Exercise Tolerance; Female; Forearm; Humans; Hyperemia; Infusions, Intra-Arterial; Male; Middle Aged; Muscle Contraction; Muscle, Skeletal; Phenylephrine; Random Allocation; Vasoconstriction
PubMed: 32822215
DOI: 10.1152/ajpheart.00532.2020 -
NeuroImage Sep 2021Revealing the structural and functional change of microvasculature is essential to match vascular response with neuronal activities in the investigation of neurovascular...
Revealing the structural and functional change of microvasculature is essential to match vascular response with neuronal activities in the investigation of neurovascular coupling. The increasing use of rhesus models in fundamental and clinical studies of neurovascular coupling presents an emerging need for a new imaging modality. Here we report a structural and functional cerebral vascular study of rhesus monkeys using an ultrafast, portable, and high resolution photoacoustic microscopic system with a long working distance and a special scanning mechanism to eliminate the relative displacement between the imaging interface and samples. We derived the structural and functional response of the cerebral vasculature to the alternating normoxic and hypoxic conditions by calculating the vascular diameter and functional connectivity. Both vasodilatation and vasoconstriction were observed in hypoxia. In addition to the change of vascular diameter, the decrease of functional connectivity is also an important phenomenon induced by the reduction of oxygen ventilatory. These results suggest that photoacoustic microscopy is a promising method to study the neurovascular coupling and cerebral vascular diseases due to the advanced features of high spatiotemporal resolution, excellent sensitivity to hemoglobin, and label-free imaging capability of observing hemodynamics.
Topics: Animals; Cerebral Cortex; Cerebrovascular Circulation; Hemodynamics; Macaca mulatta; Microscopy; Neurovascular Coupling; Photoacoustic Techniques; Vasoconstriction; Vasodilation
PubMed: 34118393
DOI: 10.1016/j.neuroimage.2021.118260 -
Haematologica Jan 2020Vaso-occlusive crisis (VOC) is a hallmark of sickle cell disease (SCD) and occurs when deoxygenated sickled red blood cells occlude the microvasculature. Any stimulus,...
Vaso-occlusive crisis (VOC) is a hallmark of sickle cell disease (SCD) and occurs when deoxygenated sickled red blood cells occlude the microvasculature. Any stimulus, such as mental stress, which decreases microvascular blood flow will increase the likelihood of red cell entrapment resulting in local vaso-occlusion and progression to VOC. Neurally mediated vasoconstriction might be the physiological link between crisis triggers and vaso-occlusion. In this study, we determined the effect of mental stress on microvascular blood flow and autonomic nervous system reactivity. Sickle cell patients and controls performed mentally stressful tasks, including a memory task, conflict test and pain anticipation test. Blood flow was measured using photoplethysmography, autonomic reactivity was derived from electrocardiography and perceived stress was measured by the State-Trait Anxiety Inventory questionnaire. Stress tasks induced a significant decrease in microvascular blood flow, parasympathetic withdrawal and sympathetic activation in all subjects. Of the various tests, pain anticipation caused the highest degree of vasoconstriction. The magnitude of vasoconstriction, sympathetic activation and perceived stress was greater during the Stroop conflict test than during the N-back memory test, indicating the relationship between magnitude of experimental stress and degree of regional vasoconstriction. Baseline anxiety had a significant effect on the vasoconstrictive response in sickle cell subjects but not in controls. In conclusion, mental stress caused vasoconstriction and autonomic nervous system reactivity in all subjects. Although the pattern of responses was not significantly different between the two groups, the consequences of vasoconstriction can be quite significant in SCD because of the resultant entrapment of sickle cells in the microvasculature. This suggests that mental stress can precipitate a VOC in SCD by causing neural-mediated vasoconstriction.
Topics: Anemia, Sickle Cell; Autonomic Nervous System; Humans; Stress, Psychological; Vascular Diseases; Vasoconstriction
PubMed: 30975906
DOI: 10.3324/haematol.2018.211391 -
The American Journal of Pathology Jan 2021Contraction of vascular smooth muscle is regulated primarily by calcium concentration and secondarily by ROCK activity within the cells. In contrast to the wealth of...
Contraction of vascular smooth muscle is regulated primarily by calcium concentration and secondarily by ROCK activity within the cells. In contrast to the wealth of information regarding regulation of calcium concentration, little is known about the spatiotemporal regulation of ROCK activity in live blood vessels. Here, we report ROCK activation in subcutaneous arterioles in a transgenic mouse line that expresses a genetically encoded ROCK biosensor based on the principle of Fӧrster resonance energy transfer by two-photon excitation in vivo imaging. Rapid vasospasm was induced upon laser ablation of arterioles, concomitant with a transient increase in calcium concentration in arteriolar smooth muscles. Unlike the increase in calcium concentration, vasoconstriction and ROCK activation continued for several minutes after irradiation. Both the ROCK inhibitor, fasudil, and the ganglionic nicotinic acetylcholine receptor blocker, hexamethonium, inhibited laser-induced ROCK activation and reduced the duration of vasospasm at the segments distant from the irradiated point. These observations suggest that vasoconstriction is initially triggered by a rapid surge of cytoplasmic calcium and then maintained by sympathetic nerve-mediated ROCK activation.
Topics: Animals; Autonomic Nervous System; Calcium Signaling; Fluorescence Resonance Energy Transfer; Mice; Mice, Inbred C57BL; Mice, Transgenic; Muscle, Smooth, Vascular; Vasoconstriction; rho-Associated Kinases
PubMed: 33069718
DOI: 10.1016/j.ajpath.2020.09.012 -
Physiological Research Jul 2018Alcohol abuse during pregnancy is a well-known factor in fetal morbidity, including smaller fetal size. We have shown that chronic hypoxia, considered the main...
Alcohol abuse during pregnancy is a well-known factor in fetal morbidity, including smaller fetal size. We have shown that chronic hypoxia, considered the main pathogenetic factor in intrauterine growth restriction, elevates fetoplacental vascular resistance (and vasoconstrictor reactivity) and thus, presumably, reduces placental blood flow. We thus hypothesized that alcohol may affect the fetus - in addition to other mechanisms - by altering fetoplacental vascular resistance and/or reactivity. Using isolated, double-perfused rat placenta model, we found that maternal alcohol intake in the last third of gestation doubled the vasoconstrictor responses to angiotensin II but did not affect resting vascular resistance. Reactivity to acute hypoxic challenges was unchanged. Chronic maternal alcohol intake in a rat model alters fetoplacental vasculature reactivity; nevertheless, these changes do not appear as serious as other detrimental effects of alcohol on the fetus.
Topics: Animals; Female; Fetal Alcohol Spectrum Disorders; In Vitro Techniques; Placental Circulation; Pregnancy; Rats, Wistar; Vasoconstriction
PubMed: 29527911
DOI: 10.33549/physiolres.933609 -
Vascular Pharmacology Nov 2015Endothelium lining the interior of cardiovascular system and most visceral organs plays an important role in vascular function. Its dysfunction occurs in some of the...
Endothelium lining the interior of cardiovascular system and most visceral organs plays an important role in vascular function. Its dysfunction occurs in some of the most challenging diseases. An important function of the endothelium is to release vasoactive substances that act on the smooth muscle to change vascular tones. Substance secretion from endocrine cells relies on membrane potentials and firing activity, while it is unclear whether the membrane potential regulates substance release from the ECs. Understanding of this requires selective intervention to membrane potentials of the endothelial cells in situ. Here we show a novel intervention to endothelial cells using the optogenetic approach. A strain of transgenic mice was developed with the Cre-loxP recombination system. These transgenic mice expressed channelrhodopsin (ChR) in endothelial cells driven by the vascular endothelial cadherin or cdh5 promoter. Linked in a tandem with YFP, the ChR expression was detected by YFP fluorescence in various endothelium-lining tissues and organs. The YFP fluorescence was observed in the lumen of blood vessels and pericardium, but not in tissues beneath the endothelium lining. Optostimulation of dissociated endothelial cells evoked inward currents and depolarization. In the isolated and perfused heart, surprisingly, optostimulation of endothelial cells produced fast, robust, reproducible and long-lasting vasoconstriction that was not blocked by either ET-1A or TXA2 receptor antagonist. Similar optical vasoconstriction was found in the isolated and perfused kidney. These results indicate that the optogenetics is an effective intervention to vascular endothelium where optostimulation produces vasoconstriction.
Topics: Animals; Endothelium, Vascular; Kidney; Membrane Potentials; Mice; Mice, Transgenic; Muscle, Smooth, Vascular; Optogenetics; Vasoconstriction
PubMed: 26015375
DOI: 10.1016/j.vph.2015.05.009 -
Physiological Reports Apr 2019We investigated the integration of sympathetic vasoconstriction and local vasodilation in the skeletal muscle and skin microvasculature of humans. In 39 healthy...
We investigated the integration of sympathetic vasoconstriction and local vasodilation in the skeletal muscle and skin microvasculature of humans. In 39 healthy volunteers, we simultaneously measured the blood flow index in the flexor carpi radialis muscle using diffuse correlation spectroscopy and the skin using laser-Doppler flowmetry. We examined the effects of acute sympathoexcitation induced by forehead cooling on relatively weak and robust vasodilatory responses during postocclusive reactive hyperemia (PORH) induced by 70-sec and 10-min arterial occlusion in the upper arm. To increase sympathetic tone during PORH, forehead cooling was begun 60 sec before the occlusion release and ended 60 sec after the release. In the 70-sec occlusion trials, acute sympathoexcitation reduced the peak and duration of vasodilation in both skeletal muscle and skin. The inhibition of vasodilation by sympathoexcitation was blunted in both tissues by the robust vasodilatory stimulation produced by the 10-min occlusion, and the degree of blunting was greater in skeletal muscle than in skin, especially the initial and peak responses. Sympathoexcitation reduced the peak vasodilation only in skin, while it accelerated the initial vasodilation only in skeletal muscle. However, the decline in vasodilation after the peak was significantly hastened in skeletal muscle, shortening the duration of the vasodilation. We conclude that, in humans, the integration of sympathetic vasoconstriction and local vasodilation has different effects in skeletal muscle and skin and is likely an important contributor to the selective control of perfusion in the microcirculations of different tissues.
Topics: Female; Forearm; Healthy Volunteers; Humans; Hyperemia; Laser-Doppler Flowmetry; Male; Microvessels; Muscle, Skeletal; Regional Blood Flow; Skin; Sympathetic Nervous System; Vasoconstriction; Vasodilation; Young Adult
PubMed: 30980512
DOI: 10.14814/phy2.14070