-
Journal of Applied Physiology... Mar 2021Bone is a highly vascularized tissue. However, despite the importance of appropriate circulation for bone health, regulation of bone blood flow remains poorly...
Bone is a highly vascularized tissue. However, despite the importance of appropriate circulation for bone health, regulation of bone blood flow remains poorly understood. Invasive animal studies suggest that sympathetic activity plays an important role in bone flow control. However, it remains unknown if bone vasculature evidences robust vasoconstriction in response to sympathoexcitatory stimuli. Here, we characterized bone blood flow in young healthy individuals [ = 13, (four females)] in response to isometric handgrip exercise (IHE) and cold pressor test (CPT). These provide a strong stimulus for active vasoconstriction in the inactive muscle, and perhaps also in the bone. During sustained IHE to fatigue and CPT, we measured blood pressure, whole leg blood flow, and tibial perfusion using near-infrared spectroscopy. Tibia perfusion was determined as oxy- and deoxyhemoglobin. For both stimuli, tibial metabolism remained constant (i.e., no change in deoxyhemoglobin) and thus tibial arterial perfusion was represented by oxyhemoglobin. During IHE, oxyhemoglobin declined (beginning -0.20 ± 1.04 μM; end -1.13 ± 3.71 μM, both < 0.01) slower than whole leg blood flow (beginning -0.85 ± 1.02 cm/s; end -2.72 ± 1.64 cm/s, both < 0.01). However, during CPT, both oxyhemoglobin (beginning -0.46 ± 1.43 μM; end -0.60 ± 1.59 μM, both < 0.01) and whole leg blood flow (beginning -1.52 ± 1.63 cm/s; end -0.69 ± 1.51 cm/s, both < 0.01) declined with a similar timecourse, even though the magnitudes of decline were smaller than during IHE. These responses are likely due to the different timecourses of sympathetically mediated vasoconstriction in bone and muscle. These results indicate that sympathetic innervation of the bone vasculature serves a functional role in the control of flow in young healthy individuals. The current study is the first one to noninvasively investigate control of bone blood perfusion in vivo in humans, on a moment-by-moment basis. Our results indicate that tibial bone vasculature demonstrates active vasoconstriction in response to sympathoexcitatory stimuli in young healthy individuals. Compared with whole leg vasculature, bone vasoconstrictor response seems to be smaller, delayed, and more variable.
Topics: Blood Pressure; Female; Hand Strength; Hemodynamics; Humans; Sympathetic Nervous System; Vasoconstriction
PubMed: 33382960
DOI: 10.1152/japplphysiol.00595.2020 -
American Journal of Physiology.... Jul 2021Angiotensin II (ANG II) is a potent vasoconstrictor and may reduce renal blood flow (RBF), causing renal hypoxia. Hypotensive hemorrhage elevates plasma ANG II levels...
Angiotensin II (ANG II) is a potent vasoconstrictor and may reduce renal blood flow (RBF), causing renal hypoxia. Hypotensive hemorrhage elevates plasma ANG II levels and is associated with increased risk of acute kidney injury. We hypothesized that ANG II antagonism prevents renal vasoconstriction and hypoxia caused by hemorrhage. Pigs were anaesthetized, surgically prepared, and randomized to intravenous losartan (1.5 mg·kg·h, = 8) or an equal volume of intravenous Ringer acetate (vehicle-treated, = 8). Hemorrhage was induced by continuous aspiration of blood to reach and sustain mean arterial pressure of <50 mmHg for 30 min. Plasma ANG II levels, hemodynamics and oxygenation were assessed 60 min prehemorrhage, 30-min after the start of hemorrhage, and 60 min posthemorrhage. Erythropoietin mRNA was analyzed in cortical and medullary tissue sampled at the end of the experiment. Hypotensive hemorrhage increased plasma ANG II levels and decreased RBF and oxygen delivery in both groups. Losartan-treated animals recovered in RBF and oxygen delivery, whereas vehicle-treated animals had persistently reduced RBF and oxygen delivery. In accordance, renal vascular resistance increased over time post hemorrhage in vehicle-treated animals but was unchanged in losartan-treated animals. Renal oxygen extraction rate and cortical erythropoietin mRNA levels increased in the vehicle group but not in the losartan group. In conclusion, ANG II antagonism alleviates prolonged renal vasoconstriction and renal hypoxia in a large animal model of hypotensive hemorrhage.
Topics: Angiotensin II Type 1 Receptor Blockers; Animals; Disease Models, Animal; Hemodynamics; Hemorrhage; Hypotension; Hypoxia; Kidney; Losartan; Male; Oxygen; Swine; Vasoconstriction
PubMed: 34009032
DOI: 10.1152/ajpregu.00073.2021 -
Internal Medicine Journal Jun 2015Reversible cerebral vasoconstriction syndrome (RCVS) is a clinical-radiological syndrome characterised by severe thunderclap headaches with or without other neurological... (Review)
Review
Reversible cerebral vasoconstriction syndrome (RCVS) is a clinical-radiological syndrome characterised by severe thunderclap headaches with or without other neurological symptoms and multifocal constriction of cerebral arteries that usually resolves spontaneously within 3 months. Most patients recover completely, but up to 10% have a permanent neurological disability and some even die. Previously RCVS has been described in many clinical contexts and under different names with the term RCVS first being suggested in 2007 to unify the group. The condition may be spontaneous, but in up to 60% of cases it is secondary to another cause, including vasoactive substances (medications and illicit drugs), blood products and the post-partum state. It is believed to have a similar pathophysiological mechanism to the posterior reversible encephalopathy syndrome (PRES), and both can occur in similar clinical contexts and are frequently associated. Treatment options include calcium channel antagonists. RCVS occurs in a broad range of clinical situations making it an increasingly recognised condition about which doctors in various specialties need to be aware.
Topics: Cerebrovascular Circulation; Headache Disorders, Primary; Humans; Syndrome; Vasoconstriction; Vasospasm, Intracranial
PubMed: 25511128
DOI: 10.1111/imj.12669 -
BJOG : An International Journal of... Nov 2015The umbilical cord provides nutrition and oxygen to the fetus. The aim of this study was to determine the effects of acetylcholine (ACh) on umbilical cords from humans...
OBJECTIVE
The umbilical cord provides nutrition and oxygen to the fetus. The aim of this study was to determine the effects of acetylcholine (ACh) on umbilical cords from humans and other mammals, and the mechanisms of ACh-mediated vasoconstriction in the human umbilical cord.
DESIGN
Human and animal umbilical cords used in vascular and cellular experiments.
SETTING
Institute for Fetology, First Hospital of Soochow University, Suzhou, China.
POPULATION
A total of 85 pregnant women, 16 Sprague Dawley rats and seven pregnant sheep.
METHODS
Umbilical cord veins and arteries from humans, rats and sheep, aortas and mesenteric arteries from rats, and mesenteric, carotid and femoral arteries from ovine fetuses were used to compare vascular functions in response to ACh and to determine the mechanisms of ACh-mediated umbilical vasoconstriction. Vascular tension and ion channel currents were measured on isolated vessels and smooth muscle cells from human umbilical cords.
MAIN OUTCOME MEASURES
Provision of new evidence to conclude that ACh-stimulated vasoconstriction is common to all umbilical cords, and cellular mechanisms are linked to potassium channels.
RESULTS
ACh caused reliable vasoconstriction in umbilical veins/arteries in humans, rats and sheep, but not in any other vessels, including fetal vessels. Atropine inhibited the effects of ACh. The mRNA of ACh-muscarinic receptor subtypes M1 -M5 was expressed in human umbilical vessels. The protein kinase C antagonist GF109203X and the calcium inhibitor nifedipine decreased ACh-induced vasoconstriction in human umbilical vessels. ACh also caused a reduction in whole-cell potassium channel currents and the single-channel current of large-conductance calcium-activated potassium (BKca) channels.
CONCLUSION
Umbilical vessels are significantly different from other vessels in their response to ACh. BKca channels in smooth muscle cells may play important roles in ACh-mediated vasoconstriction in human umbilical cords. This information may be important for fetal medicine and practice with regard to the effect on fetal development of umbilical vascular functions.
Topics: Acetylcholine; Animals; China; Cholinergic Agents; Female; Humans; Pregnancy; Rats; Rats, Sprague-Dawley; Receptors, Muscarinic; Sheep; Sheep, Domestic; Umbilical Veins; Vasoconstriction
PubMed: 25403992
DOI: 10.1111/1471-0528.13144 -
Acta Physiologica (Oxford, England) Sep 2017The control of renal vascular tone is important for the regulation of salt and water balance, blood pressure and the protection against damaging elevated glomerular... (Review)
Review
The control of renal vascular tone is important for the regulation of salt and water balance, blood pressure and the protection against damaging elevated glomerular pressure. The K conductance is a major factor in the regulation of the membrane potential (V ) in vascular smooth muscle (VSMC) and endothelial cells (EC). The vascular tone is controlled by V via its effect on the opening probability of voltage-operated Ca channels (VOCC) in VSMC. When K conductance increases V becomes more negative and vasodilation follows, while deactivation of K channels leads to depolarization and vasoconstriction. K channels in EC indirectly participate in the control of vascular tone by endothelium-derived vasodilation. Therefore, by regulating the tone of renal resistance vessels, K channels have a potential role in the control of fluid homoeostasis and blood pressure as well as in the protection of the renal parenchyma. The main classes of K channels (calcium activated (K ), inward rectifier (K ), voltage activated (K ) and ATP sensitive (K )) have been found in the renal vessels. In this review, we summarize results available in the literature and our own studies in the field. We compare the ambiguous in vitro and in vivo results. We discuss the role of single types of K channels and the integrated function of several classes. We also deal with the possible role of renal vascular K channels in the pathophysiology of hypertension, diabetes mellitus and sepsis.
Topics: Animals; Humans; Kidney; Muscle, Smooth, Vascular; Potassium Channels; Vasoconstriction; Vasodilation
PubMed: 28371470
DOI: 10.1111/apha.12882 -
Journal of the Neurological Sciences Feb 2018We report four fatal cases of fulminant reversible cerebral vasoconstriction syndrome, all initially diagnosed as primary central nervous system vasculitis and treated...
We report four fatal cases of fulminant reversible cerebral vasoconstriction syndrome, all initially diagnosed as primary central nervous system vasculitis and treated with corticosteroids. Although reversible cerebral vasoconstriction syndrome is usually self-limiting without permanent neurologic deficits, rarely it can be fatal and worse outcomes have been associated with corticosteroid treatment.
Topics: Angiography, Digital Subtraction; Brain; Cerebrovascular Disorders; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Tomography Scanners, X-Ray Computed; Vasoconstriction; Young Adult
PubMed: 29406896
DOI: 10.1016/j.jns.2017.12.009 -
Brain-Derived Extracellular Vesicles Induce Vasoconstriction and Reduce Cerebral Blood Flow in Mice.Journal of Neurotrauma Jun 2022Traumatic brain injury (TBI) impairs cerebrovascular autoregulation and reduces cerebral blood flow (CBF), leading to ischemic secondary injuries. We have shown that...
Traumatic brain injury (TBI) impairs cerebrovascular autoregulation and reduces cerebral blood flow (CBF), leading to ischemic secondary injuries. We have shown that injured brains release brain-derived extracellular vesicles (BDEVs) into circulation, where they cause a systemic hypercoagulable state that rapidly turns into consumptive coagulopathy. The BDEVs induce endothelial injury and permeability, leading to the hypothesis that they contribute to TBI-induced cerebrovascular dysregulation. In a study designed to test this hypothesis, we detected circulating BDEVs in C57BL/6J mice subjected to severe TBI, reaching peak levels of 3 × 10/μL at 3 h post-injury (71.2 ± 21.5% of total annexin V-binding EVs). We further showed in an adaptive transfer model that 41.7 ± 5.8% of non-injured mice died within 6 h after being infused with 3 × 10/μL of BDEVs. The BDEVs transmigrated through the vessel walls, induced rapid vasoconstriction by inducing calcium influx in vascular smooth muscle cells, and reduced CBF by 93.8 ± 5.6% within 30 min after infusion. The CBF suppression was persistent in mice that eventually died, but it recovered quickly in surviving mice. It was prevented by the calcium channel blocker nimodipine. When being separated, neither protein nor phospholipid components from the lethal number of BDEVs induced vasoconstriction, reduced CBF, and caused death. These results demonstrate a novel vasoconstrictive activity of BDEVs that depends on the structure of BDEVs and contributes to TBI-induced disseminated cerebral ischemia and sudden death.
Topics: Animals; Brain; Brain Injuries, Traumatic; Cerebrovascular Circulation; Extracellular Vesicles; Mice; Mice, Inbred C57BL; Vasoconstriction
PubMed: 35316073
DOI: 10.1089/neu.2021.0274 -
Oxidative Medicine and Cellular... 2021We explored the role of ROS in cold-induced vasoconstriction and corresponding mechanism.
PURPOSE
We explored the role of ROS in cold-induced vasoconstriction and corresponding mechanism.
METHODS
Three experiments were performed. First, we measured blood flow in human hands before and after cold exposure. Second, 24 mice were randomly divided into 3 groups: 8 mice received saline injection, 8 received subcutaneous Tempol injection, and 8 received intrathecal Tempol injection. After 30 min, we determined blood flow in the skin before and after cold exposure. Finally, we used Tempol, CCG-1423, and Go 6983 to pretreat HAVSMCs and HUVECs for 24 h. Then, cells in the corresponding groups were exposed to cold (6 h, 4°C). After cold exposure, the cytoskeleton was stained. Intracellular Ca and ROS levels were measured by flow cytometry and fluorescence microscopy. We measured protein expression via Western blotting.
RESULTS
In the first experiment, after cold exposure, maximum skin blood flow decreased to 118.4 ± 50.97 flux units. Then, Tempol or normal saline pretreatment did not change skin blood flow. Unlike intrathecal Tempol injection, subcutaneous Tempol injection increased skin blood flow after cold exposure. Finally, cold exposure for 6 h shrank the cells, making them narrower, and increased intracellular Ca and ROS levels in HUVECs and HAVSMCs. Tempol reduced cell shrinkage and decreased intracellular Ca levels. In addition, Tempol decreased intracellular ROS levels. Cold exposure increased RhoA, Rock1, p-MLC-2, ET-1, iNOS, and p-PKC expression and decreased eNOS expression. Tempol or CCG-1423 pretreatment decreased RhoA, Rock1, and p-MLC-2 levels in HAVSMCs. Furthermore, Tempol or Go 6983 pretreatment decreased ET-1, iNOS, and p-PKC expression and increased eNOS expression in HUVECs.
CONCLUSION
ROS mediate the vasoconstrictor response within the cold-induced vascular response, and ROS in blood vessel tissues rather than nerve fibers are involved in vasoconstriction via the ROS/RhoA/ROCK1 and ROS/PKC/ET-1 pathways in VSMCs and endothelial cells.
Topics: Adult; Animals; Cold Temperature; Female; Humans; Male; Mice; Reactive Oxygen Species; Vasoconstriction
PubMed: 34868457
DOI: 10.1155/2021/8578452 -
Revista Medica de Chile Jun 2023Pulmonary arterial hypertension is characterized by increased mean pulmonary arterial pressure, resistance, and pathological remodeling of pulmonary arteries. Calcium... (Review)
Review
Pulmonary arterial hypertension is characterized by increased mean pulmonary arterial pressure, resistance, and pathological remodeling of pulmonary arteries. Calcium entry from the extracellular to the intracellular space through voltage-dependent and -independent channels play a major role in the increase of contractility of pulmonary arteries and in the loss of regulation of the proliferative behavior of the cells from the different layers of the pulmonary arterial wall. In doing so, these channels contribute to enhanced vasoconstriction of pulmonary arteries and their pathological remodeling. This review aims to summarize the evidence obtained from animal and cellular models regarding the involvement of the main plasma membrane calcium channels in these key pathophysiological processes for pulmonary arterial hypertension, discussing the potential value as pharmacological targets for therapies in the present and the future.
Topics: Humans; Hypertension, Pulmonary; Calcium Channels; Animals; Calcium Signaling; Calcium Channel Blockers; Signal Transduction; Pulmonary Artery; Vasoconstriction
PubMed: 38801384
DOI: 10.4067/s0034-98872023000600753 -
Acta Physiologica (Oxford, England) Feb 2018Sphingosine-1-phosphate (S1P) influences resistance vessel function and is implicated in renal pathological processes. Previous studies revealed that S1P evoked potent...
AIM
Sphingosine-1-phosphate (S1P) influences resistance vessel function and is implicated in renal pathological processes. Previous studies revealed that S1P evoked potent vasoconstriction of the pre-glomerular microvasculature, but the underlying mechanisms remain incompletely defined. We postulated that S1P-mediated pre-glomerular microvascular vasoconstriction involves activation of voltage-dependent L-type calcium channels (L-VDCC) and the rho/rho kinase pathway.
METHODS
Afferent arteriolar reactivity was assessed in vitro using the blood-perfused rat juxtamedullary nephron preparation, and diameter was measured during exposure to physiological and pharmacological agents.
RESULTS
Exogenous S1P (10 -10 mol L ) evoked concentration-dependent vasoconstriction of afferent arterioles. Superfusion with nifedipine, a L-VDCC blocker, increased arteriolar diameter by 39 ± 18% of baseline and significantly attenuated the S1P-induced vasoconstriction. Superfusion with the rho kinase inhibitor, Y-27632, increased diameter by 60 ± 12% of baseline and also significantly blunted vasoconstriction by S1P. Combined nifedipine and Y-27632 treatment significantly inhibited S1P-induced vasoconstriction over the entire concentration range tested. In contrast, depletion of intracellular Ca stores with the Ca -ATPase inhibitors, thapsigargin or cyclopiazonic acid, did not alter the S1P-mediated vasoconstrictor profile. Scavenging reactive oxygen species (ROS) or inhibition of nicotinamide adenine dinucleotide phosphate oxidase activity significantly attenuated S1P-mediated vasoconstriction.
CONCLUSION
Exogenous S1P elicits potent vasoconstriction of rat afferent arterioles. These data also demonstrate that S1P-mediated pre-glomerular vasoconstriction involves activation of L-VDCC, the rho/rho kinase pathway and ROS. Mobilization of Ca from intracellular stores is not required for S1P-mediated vasoconstriction. These studies reveal a potential role for S1P in the modulation of renal microvascular tone.
Topics: Animals; Arterioles; Kidney; Lysophospholipids; Male; Muscle, Smooth, Vascular; Rats; Rats, Sprague-Dawley; Renal Circulation; Sphingosine; Vasoconstriction
PubMed: 28640982
DOI: 10.1111/apha.12913