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Experimental Gerontology Jul 2020Changes of vasoconstriction may be measured non-invasively using pulse transit time. This study assessed the sensitivity, test-retest reliability and validity of pulse...
OBJECTIVES
Changes of vasoconstriction may be measured non-invasively using pulse transit time. This study assessed the sensitivity, test-retest reliability and validity of pulse transit time during vasoconstriction provocation and active standing, and the predictive value of pulse transit time for blood pressure drop.
METHODS
Fifty-five younger (age < 65 years) and 31 older adults (age > 70 years) underwent electrocardiography, wrist and finger photoplethysmography and continuous blood pressure and total peripheral resistance measurements during vasoconstriction provocation using a cold pressor test (21 younger adults), or active stand tests (all other participants). Pulse transit time was defined as the time lag between the electrocardiography R-peak and the peak in the photoplethysmography first derivative; sensitivity as a significant decrease relative to baseline; test-retest reliability as the intra class correlation between different repeats of the same test; validity as the association between peripheral resistance and pulse transit time; predictive value as the association between supine resting pulse transit time and mean arterial pressure drop during active standing.
RESULTS
Finger pulse transit time was sensitive and reliable (ICC 0.2-0.8) during vasoconstriction provocation, but wrist pulse transit time was poorly reliable (ICC 0-0.5); only finger pulse transit time was sensitive to and reliable (ICC 0.4-0.8) during active standing in both younger and older adults. Finger pulse transit time was not associated with total peripheral resistance. Supine resting pulse transit time had predictive value for blood pressure drop during active standing in older adults (β -0.16; p 0.025).
CONCLUSIONS
Pulse transit time was sensitive to and reliable during vasoconstriction provocation and active standing, but did not significantly differ between younger and older adults. Pulse transit time could not be demonstrated to particularly reflect vasoconstriction, but it had predictive value for blood pressure drop during active standing.
Topics: Aged; Blood Pressure; Humans; Photoplethysmography; Pulse Wave Analysis; Reproducibility of Results; Vasoconstriction
PubMed: 32247853
DOI: 10.1016/j.exger.2020.110938 -
American Journal of Respiratory Cell... Jun 2020
Topics: Cholesterol; Humans; Hypertension, Pulmonary; Hypoxia; Pulmonary Artery; Vasoconstriction
PubMed: 32011912
DOI: 10.1165/rcmb.2020-0020ED -
American Journal of Physiology.... Jun 2021Herein we report in a sample of healthy young men ( = 14) and women ( = 12) that hyperinsulinemia induces time-dependent decreases in total peripheral resistance and its...
Herein we report in a sample of healthy young men ( = 14) and women ( = 12) that hyperinsulinemia induces time-dependent decreases in total peripheral resistance and its contribution to the maintenance of blood pressure. In the same participants, we observe profound vasodilatory effects of insulin in the lower limb despite concomitant activation of the sympathetic nervous system. We hypothesized that this prominent peripheral vasodilation is possibly due to the ability of the leg vasculature to escape sympathetic vasoconstriction during systemic insulin stimulation. Consistent with this notion, we demonstrate in a subset of healthy men ( = 9) and women ( = 7) that systemic infusion of insulin blunts sympathetically mediated leg vasoconstriction evoked by a cold pressor test, a well-established sympathoexcitatory stimulus. Further substantiating this observation, we show in mouse aortic rings that insulin exposure suppresses epinephrine and norepinephrine-induced vasoconstriction. Notably, we found that such insulin-suppressing effects on catecholamine-induced constriction are diminished following β-adrenergic receptor blockade. In accordance, we also reveal that insulin augments β-adrenergic-mediated vasorelaxation in isolated arteries. Collectively, these findings support the idea that sympathetic vasoconstriction can be attenuated during systemic hyperinsulinemia in the leg vasculature of both men and women and that this phenomenon may be in part mediated by potentiation of β-adrenergic vasodilation neutralizing α-adrenergic vasoconstriction.
Topics: Adrenergic Agents; Adult; Blood Pressure; Female; Humans; Hyperinsulinism; Male; Norepinephrine; Regional Blood Flow; Sympathetic Nervous System; Vascular Resistance; Vasoconstriction
PubMed: 33851554
DOI: 10.1152/ajpregu.00018.2021 -
Anesthesia Progress 2018To assess the effect of epinephrine-containing local anesthetics on vasoconstriction, we immunohistochemically measured the intravascular lumen area in different regions...
To assess the effect of epinephrine-containing local anesthetics on vasoconstriction, we immunohistochemically measured the intravascular lumen area in different regions of the mandible. Twelve male Wistar rats were used. General anesthesia was induced and maintained with sevoflurane. Infiltration anesthesia was performed with 0.2 mL of epinephrine-free 2% lidocaine (E-) near the left mandibular first molar and with 0.2 mL of epinephrine-containing 2% lidocaine (E+) near the right mandibular first molar. After decalcification, the specimens were paraffinized, and thin sections were prepared and immunohistologically stained with an antismooth muscle actin antibody. The intravascular lumen area was measured in the mucosa, periodontal membrane, Haversian/Volkmann's canal, and bone marrow. A Mann-Whitney U test was used for statistical processing, and p < .05 was considered to indicate a statistically significant difference. In the oral mucosa and the periodontal membrane, E+ had a significantly smaller vascular lumen area than E-. In the Haversian/Volkmann's canal and the bone marrow, no significant intergroup difference was observed in the intravascular lumen area. We postulate that this is due to a low smooth muscle content of blood vessels in the mandible and suggest that the vasoconstrictive effect of epinephrine-containing local anesthetics within the mandible is ineffective.
Topics: Actins; Anesthetics, Local; Animals; Biomarkers; Epinephrine; Injections; Lidocaine; Male; Mandible; Muscle, Smooth, Vascular; Rats, Wistar; Vasoconstriction; Vasoconstrictor Agents
PubMed: 30715934
DOI: 10.2344/anpr-65-03-15 -
Pharmacology & Therapeutics May 2020Numerous mediators and drugs regulate blood flow or arterial pressure by acting on vascular tone, involving cyclic nucleotide intracellular pathways. These signals lead... (Review)
Review
Numerous mediators and drugs regulate blood flow or arterial pressure by acting on vascular tone, involving cyclic nucleotide intracellular pathways. These signals lead to regulation of several cellular effectors, including ion channels that tune cell membrane potential, Ca influx and vascular tone. The characterization of these vasocontrictive or vasodilating mechanisms has grown in complexity due to i) the variety of ion channels that are expressed in both vascular endothelial and smooth muscle cells, ii) the heterogeneity of responses among the various vascular beds, and iii) the number of molecular mechanisms involved in cyclic nucleotide signalling in health and disease. This review synthesizes key data from literature that highlight ion channels as physiologically relevant effectors of cyclic nucleotide pathways in the vasculature, including the characterization of the molecular mechanisms involved. In smooth muscle cells, cation influx or chloride efflux through ion channels are associated with vasoconstriction, whereas K efflux repolarizes the cell membrane potential and mediates vasodilatation. Both categories of ion currents are under the influence of cAMP and cGMP pathways. Evidence that some ion channels are influenced by CN signalling in endothelial cells will also be presented. Emphasis will also be put on recent data touching a variety of determinants such as phosphodiesterases, EPAC and kinase anchoring, that complicate or even challenge former paradigms.
Topics: Animals; Arteries; Endothelium, Vascular; Humans; Ion Channels; Muscle, Smooth, Vascular; Nucleotides, Cyclic; Signal Transduction; Vasoconstriction; Vasodilation
PubMed: 32068004
DOI: 10.1016/j.pharmthera.2020.107499 -
Neurological Sciences : Official... Sep 2020Noninvasive temperature modulation by localized neck cooling might be desirable in the prehospital phase of acute hypoxic brain injuries. While combined head and neck...
INTRODUCTION
Noninvasive temperature modulation by localized neck cooling might be desirable in the prehospital phase of acute hypoxic brain injuries. While combined head and neck cooling induces significant discomfort, peripheral vasoconstriction, and blood pressure increase, localized neck cooling more selectively targets blood vessels that supply the brain, spares thermal receptors of the face and skull, and might therefore cause less discomfort cardiovascular side effects compared to head- and neck cooling. The purpose of this study is to assess the effects of noninvasive selective neck cooling on cardiovascular parameters and cerebral blood flow velocity (CBFV).
METHODS
Eleven healthy persons (6 women, mean age 42 ± 11 years) underwent 90 min of localized dorsal and frontal neck cooling (EMCOOLS Brain.Pad™) without sedation. Before and after cooling onset, and after every 10 min of cooling, we determined rectal, tympanic, and neck skin temperatures. Before and after cooling onset, after 60- and 90-min cooling, we monitored RR intervals (RRI), systolic, diastolic blood pressures (BPsys, BPdia), laser Doppler skin blood flow (SBF) at the index finger pulp, and CBFV at the proximal middle cerebral artery (MCA). We compared values before and during cooling by analysis of variance for repeated measurements with post hoc analysis (significance: p < 0.05).
RESULTS
Neck skin temperature dropped significantly by 9.2 ± 4.5 °C (minimum after 40 min), while tympanic temperature decreased by only 0.8 ± 0.4 °C (minimum after 50 min), and rectal temperature by only 0.2 ± 0.3 °C (minimum after 60 min of cooling). Index finger SBF decreased (by 83.4 ± 126.0 PU), BPsys and BPdia increased (by 11.2 ± 13.1 mmHg and 8.0 ± 10.1 mmHg), and heart rate slowed significantly while MCA-CBFV remained unchanged during cooling.
CONCLUSIONS
While localized neck cooling prominently lowered neck skin temperature, it had little effect on tympanic temperature but significantly increased BP which may have detrimental effects in patients with acute brain injuries.
Topics: Adult; Blood Pressure; Body Temperature; Female; Humans; Hypothermia, Induced; Middle Aged; Neck; Vasoconstriction
PubMed: 32219592
DOI: 10.1007/s10072-020-04349-x -
Hypertension (Dallas, Tex. : 1979) May 2022Major depressive disorder (MDD) is associated with sympathetic overactivity and alterations in peripheral adrenergic receptor function; however, no studies have directly...
BACKGROUND
Major depressive disorder (MDD) is associated with sympathetic overactivity and alterations in peripheral adrenergic receptor function; however, no studies have directly assessed vasoconstrictor responsiveness in adults with MDD. We tested the hypotheses that β-adrenergic receptor-mediated vasodilation would be blunted in adults with MDD compared with healthy nondepressed adults (HA) and would functionally contribute to exaggerated norepinephrine-induced vasoconstriction.
METHODS
In 13 HA (8 female; 24±4 years) and in 12 adults with MDD (8 female; 22±3 yrs), red blood cell flux was measured during graded intradermal microdialysis perfusion of the β-adrenergic receptor agonist isoproterenol (10 to 10 mol/L) and, separately, during the perfusion of norepinephrine (10 to 10 mol/L), alone and in combination with the β-adrenergic receptor antagonist propranolol (2 mmol/L). Nonadrenergic vasoconstriction was assessed via perfusion of angiotensin II (10 to 10 mol/L).
RESULTS
Isoproterenol-induced vasodilation was blunted in adults with MDD (188.9±70.1 HA versus 128.3±39.4 au MDD, =0.025). Net norepinephrine-induced vasoconstriction was exaggerated in adults with MDD (-0.16±0.54 HA versus -0.75±0.56 au MDD, =0.014); however, there were no group differences in angiotensin II-induced vasoconstriction. Propranolol potentiated norepinephrine-induced vasoconstriction in HA (-0.16±0.54 norepinephrine versus -1.60±1.40 au propranolol, <0.01) but had no effect in adults with MDD (-0.75±0.56 norepinephrine versus -1.58±1.56 au propranolol, =0.08).
CONCLUSIONS
β-adrenergic receptor-mediated microvascular vasodilation was blunted in adults with MDD and contributed to exaggerated adrenergic vasoconstriction. The relative loss of the vasoprotective effect of β-adrenergic receptor-mediated vasodilation may contribute to increased peripheral resistance, thereby driving the development of hypertension in adults with MDD.
Topics: Adult; Angiotensin II; Depressive Disorder, Major; Female; Humans; Isoproterenol; Male; Norepinephrine; Propranolol; Receptors, Adrenergic, beta; Vasoconstriction; Vasodilation
PubMed: 35232218
DOI: 10.1161/HYPERTENSIONAHA.122.18985 -
Scientific Reports Feb 2022Inhibition of Notch signaling in macrophages is known to reduce inflammation, however, its role in regulating vascular hyporeactivity in sepsis is unknown. Thus we aimed...
Inhibition of Notch signaling in macrophages is known to reduce inflammation, however, its role in regulating vascular hyporeactivity in sepsis is unknown. Thus we aimed to evaluate the effect of sepsis on vascular Notch signaling. Polymicrobial sepsis was induced by caecal ligation and puncture (CLP) in mice. mRNA expressions of Notch receptors (Notch1,3) and ligands (Jag1, Dll4), and downstream effector genes (Hey1, MLCK, MYPT1) were assessed by RT-qPCR. Protein level of activated Notch (NICD) was assessed by Western blot and immuno-histochemistry. Isometric tension in isolated aortic rings was measured by wire myography.CLP down-regulated aortic expression of Notch3, Jag1 and Dll4 as compared to control mice. Additionally, the protein level of NICD was found to be lesser in aortic tissue sections from CLP mice. Expression of Hey1 and MLCK were attenuated whereas MYPT1 expression was increased in septic mouse aorta. DAPT pretreatment did not improve CLP-induced vascular hyporeactivity to NA, CaCl and high K (80 mM), rather significantly attenuated the aortic response to these vasoconstrictors in control mice. Treatment with 1400 W reversed attenuated Notch3 (but not Jag1 and MLCK) expression in septic mouse aorta. In conclusion, sepsis significantly attenuated the Notch (especially Notch3) signaling in mouse aorta along with reduction in contractile gene expression and vasoconstriction response. Further, iNOS/NO pathway was involved in sepsis-induced down-regulation of Notch3 receptor. Thus systemic inhibition of Notch signaling during sepsis may have serious impact on sepsis-induced vascular hyporeactivity.
Topics: Animals; Aorta; Arterial Pressure; Down-Regulation; Mice; Nitric Oxide; Nitric Oxide Synthase Type II; Receptor, Notch3; Sepsis; Signal Transduction; Vasoconstriction
PubMed: 35190630
DOI: 10.1038/s41598-022-06949-3 -
The Journal of Physiology Mar 2021Iron acts as a cofactor in the stabilization of the hypoxic-inducible factor family, and plays an influential role in the modulation of hypoxic pulmonary...
KEY POINTS
Iron acts as a cofactor in the stabilization of the hypoxic-inducible factor family, and plays an influential role in the modulation of hypoxic pulmonary vasoconstriction. It is uncertain whether iron regulation is altered in lowlanders during either (1) ascent to high altitude, or (2) following partial acclimatization, when compared to high-altitude adapted Sherpa. During ascent to 5050 m, the rise in pulmonary artery systolic pressure (PASP) was blunted in Sherpa, compared to lowlanders; however, upon arrival to 5050 m, PASP levels were comparable in both groups, but the reduction in iron bioavailability was more prevalent in lowlanders compared to Sherpa. Following partial acclimatization to 5050 m, there were differential influences of iron status manipulation (via iron infusion or chelation) at rest and during exercise between lowlanders and Sherpa on the pulmonary vasculature.
ABSTRACT
To examine the adaptational role of iron bioavailability on the pulmonary vascular responses to acute and chronic hypobaric hypoxia, the haematological and cardiopulmonary profile of lowlanders and Sherpa were determined during: (1) a 9-day ascent to 5050 m (20 lowlanders; 12 Sherpa), and (2) following partial acclimatization (11 ± 4 days) to 5050 m (18 lowlanders; 20 Sherpa), where both groups received an i.v. infusion of either iron (iron (iii)-hydroxide sucrose) or an iron chelator (desferrioxamine). During ascent, there were reductions in iron status in both lowlanders and Sherpa; however, Sherpa appeared to demonstrate a more efficient capacity to mobilize stored iron, compared to lowlanders, when expressed as a Δhepcidin per unit change in either body iron or the soluble transferrin receptor index, between 3400-5050 m (P = 0.016 and P = 0.029, respectively). The rise in pulmonary artery systolic pressure (PASP) was blunted in Sherpa, compared to lowlanders during ascent; however, PASP was comparable in both groups upon arrival to 5050 m. Following partial acclimatization, despite Sherpa demonstrating a blunted hypoxic ventilatory response and greater resting hypoxaemia, they had similar hypoxic pulmonary vasoconstriction when compared to lowlanders at rest. Iron-infusion attenuated PASP in both groups at rest (P = 0.005), while chelation did not exaggerate PASP in either group at rest or during exaggerated hypoxaemia ( = 67 mmHg). During exercise at 25% peak wattage, PASP was only consistently elevated in Sherpa, which persisted following both iron infusion or chelation. These findings provide new evidence on the complex interplay of iron regulation on pulmonary vascular regulation during acclimatization and adaptation to high altitude.
Topics: Acclimatization; Altitude; Humans; Hypoxia; Iron; Vasoconstriction
PubMed: 33442904
DOI: 10.1113/JP281114 -
Sheng Li Xue Bao : [Acta Physiologica... Aug 2021Arachidonic acids (AA) widely exist in multiple organs and can be metabolized into small lipid molecules with strong biological functions through several pathways. Among... (Review)
Review
Arachidonic acids (AA) widely exist in multiple organs and can be metabolized into small lipid molecules with strong biological functions through several pathways. Among them, epoxyeicosatrienoic acids (EETs) and 20-hydroxyeicosatetraenoic acid (20-HETE), which are produced by cytochrome P450 enzymes, have attracted a lot of attentions, especially in vascular homeostasis. The regulation of vascular function is the foundation of vascular homeostasis, which is mainly achieved by manipulating the vascular structure and biological function. In the past 30 years, the roles of EETs and 20-HETE in the regulation of vascular function have been widely explored. In this review, we discussed the effects of EETs and 20-HETE on angiogenesis and vascular inflammation, respectively. Generally, EETs can dilate blood vessels and inhibit vascular inflammation, while 20-HETE can induce vasoconstriction and vascular inflammation. Interestingly, both EETs and 20-HETE can promote angiogenesis. In addition, the roles of EETs and 20-HETE in several vascular diseases, such as hypertension and cardiac ischemia, were discussed. Finally, the therapeutic perspectives of EETs and 20-HETE for vascular diseases were also summarized.
Topics: Arachidonic Acid; Arachidonic Acids; Cytochrome P-450 Enzyme System; Humans; Hydroxyeicosatetraenoic Acids; Hypertension; Vasoconstriction
PubMed: 34405219
DOI: No ID Found