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Journal of Applied Physiology... Jul 2017Sex differences in the neurovascular control of blood pressure and vascular resistance have been reported. However, the mechanisms underlying the modulatory influence of...
Sex differences in the neurovascular control of blood pressure and vascular resistance have been reported. However, the mechanisms underlying the modulatory influence of sex have not been fully elucidated. Nitric oxide (NO) has been shown to inhibit sympathetic vasoconstriction in resting and contracting skeletal muscle, and estrogen modulates NO synthase (NOS) expression and NO bioavailability. Therefore NO-mediated inhibition of sympathetic vasoconstriction may be enhanced in females. Thus the purpose of the present study was to investigate the hypothesis that sympathetic vasoconstrictor responsiveness would be blunted and NO-mediated inhibition of sympathetic vasoconstriction would be enhanced in females compared with males. Male (M; = 8) and female (F; = 10) Sprague-Dawley rats were anesthetized and surgically instrumented for measurement of arterial blood pressure and femoral artery blood flow and stimulation of the lumbar sympathetic chain. The percentage change of femoral vascular conductance in response to sympathetic chain stimulation delivered at 2 and 5 Hz was determined at rest and during triceps surae muscle contraction before (control) and after NOS blockade [-nitro-l-arginine methyl ester (l-NAME), 10 mg/kg iv]. At rest, sympathetic vasoconstrictor responsiveness was augmented ( < 0.05) in female compared with male rats at 2 Hz [F: -33 ± 8% (SD); M: -26 ± 6%] but was not different at 5 Hz (F: -55 ± 7%; M: -47 ± 7%). During muscle contraction, evoked vasoconstriction was similar ( > 0.05) in females and males at 2 Hz (F: -12 ± 5%; M: -13 ± 5%) but was blunted ( < 0.05) in females compared with males at 5 Hz (F: -24 ± 5%; M: -34 ± 8%). l-NAME increased ( < 0.05) sympathetic vasoconstrictor responsiveness in both groups at rest and during contraction. Contraction-mediated inhibition of vasoconstriction (sympatholysis) was enhanced ( < 0.05) in females compared with males; however, sympatholysis was not different ( > 0.05) between males and females in the presence of NOS blockade, indicating that NO-mediated sympatholysis was augmented in female rats. These data suggest that sex modulates sympathetic vascular control in resting and contracting skeletal muscle and that a portion of the enhanced sympatholysis in female rats was NO dependent. Sex differences in the neurovascular regulation of blood pressure and vascular resistance have been documented. However, our understanding of the underlying mechanisms that mediate these differences is incomplete. The present study demonstrates that female rats have an enhanced capacity to inhibit sympathetic vasoconstriction during exercise (sympatholysis) and that NO mediates a portion of the enhanced sympatholysis.
Topics: Adrenergic Fibers; Animals; Female; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide; Rats; Rats, Sprague-Dawley; Sex Characteristics; Vasoconstriction; Vasoconstrictor Agents
PubMed: 28473610
DOI: 10.1152/japplphysiol.00139.2017 -
Physiological Research Jun 2018The heavy impact of obesity on the development and progression of cardiovascular disease has sparked sustained efforts to uncover the mechanisms linking excess adiposity... (Review)
Review
The heavy impact of obesity on the development and progression of cardiovascular disease has sparked sustained efforts to uncover the mechanisms linking excess adiposity to vascular dysfunction. Impaired vasodilator reactivity has been recognized as an early hemodynamic abnormality in obese patients, but also increased vasoconstrictor tone importantly contributes to their vascular damage. In particular, upregulation of the endothelin (ET)-1 system, consistently reported in these patients, might accelerate atherosclerosis and its complication, given the pro-inflammatory and mitogenic properties of ET-1. In recent years, a number of gut hormones, in addition to their role as modulators of food intake, energy balance, glucose and lipid metabolism, and insulin secretion and action, have demonstrated favorable vascular actions. They increase the bioavailability of vasodilator mediators like nitric oxide, but they have also been shown to inhibit the ET-1 system. These features make gut hormones promising tools for targeting both the metabolic and cardiovascular complications of obesity, a view supported by recent large-scale clinical trials indicating that novel drugs for type 2 diabetes with cardiovascular potential may translate into clinically significant advantages. Therefore, there is real hope that better understanding of the properties of gut-derived substances might provide more effective therapies for the obesity-related cardiometabolic syndrome.
Topics: Anti-Obesity Agents; Diabetes Mellitus, Type 2; Endothelin-1; Gastrointestinal Hormones; Humans; Insulin Resistance; Obesity; Peptide Hormones; Vasoconstriction; Vasoconstrictor Agents
PubMed: 29947529
DOI: 10.33549/physiolres.933821 -
Neuroscience May 2016The brain possesses two intricate mechanisms that fulfill its continuous metabolic needs: cerebral autoregulation, which ensures constant cerebral blood flow over a wide... (Review)
Review
The brain possesses two intricate mechanisms that fulfill its continuous metabolic needs: cerebral autoregulation, which ensures constant cerebral blood flow over a wide range of arterial pressures and functional hyperemia, which ensures rapid delivery of oxygen and glucose to active neurons. Over the past decade, a number of important studies have identified astrocytes as key intermediaries in neurovascular coupling (NVC), the mechanism by which active neurons signal blood vessels to change their diameter. Activity-dependent increases in astrocytic Ca(2+) activity are thought to contribute to the release of vasoactive substances that facilitate arteriole vasodilation. A number of vasoactive signals have been identified and their role on vessel caliber assessed both in vitro and in vivo. In this review, we discuss mechanisms implicating astrocytes in NVC-mediated vascular responses, limitations encountered as a result of the challenges in maintaining all the constituents of the neurovascular unit intact and deliberate current controversial findings disputing a main role for astrocytes in NVC. Finally, we briefly discuss the potential role of pericytes and microglia in NVC-mediated processes.
Topics: Animals; Astrocytes; Calcium Signaling; Microglia; Neurovascular Coupling; Pericytes; Vasoconstriction; Vasodilation
PubMed: 25843438
DOI: 10.1016/j.neuroscience.2015.03.064 -
American Journal of Physiology. Heart... Aug 2021Electronic cigarettes (E-cigs) have been promoted as harm-free or less risky than smoking, even for women during pregnancy. These claims are made largely on E-cig...
Electronic cigarettes (E-cigs) have been promoted as harm-free or less risky than smoking, even for women during pregnancy. These claims are made largely on E-cig aerosol having fewer number of toxic chemicals compared with cigarette smoke. Given that even low levels of smoking are found to produce adverse birth outcomes, we sought to test the hypothesis that vaping during pregnancy (with or without nicotine) would not be harm-free and would result in vascular dysfunction that would be evident in offspring during adolescent and/or adult life. Pregnant female Sprague Dawley rats were exposed to E-cig aerosol (1 h/day, 5 days/wk, starting on until pups were weaned) using e-liquid with 0 mg/mL (E-cig0) or 18 mg/mL nicotine (E-cig18) and compared with ambient air-exposed controls. Body mass at birth and at weaning were not different between groups. Assessment of middle cerebral artery (MCA) reactivity revealed a 51%-56% reduction in endothelial-dependent dilation response to acetylcholine (ACh) for both E-cig0 and E-cig18 in 1-mo, 3-mo (adolescent), and 7-mo-old (adult) offspring ( < 0.05 compared with air, all time points). MCA responses to sodium nitroprusside (SNP) and myogenic tone were not different across groups, suggesting that endothelial-independent responses were not altered. The MCA vasoconstrictor response (5-hydroxytryptamine, 5-HT) was also not different across treatment and age groups. These data demonstrate that maternal vaping during pregnancy is not harm-free and confers significant cerebrovascular health risk/dysfunction to offspring that persists into adult life. These data established that vaping electronic cigarettes during pregnancy, with or without nicotine, is not safe and confers significant risk potential to the cerebrovascular health of offspring in early and adult life. A key finding is that vaping without nicotine does not protect offspring from cerebrovascular dysfunction and results in the same level of cerebrovascular dysfunction (compared with maternal vaping with nicotine), indicating that the physical and/or chemical properties from the base solution (other than nicotine) are responsible for the cerebrovascular dysfunction that we observed. Listen to this article's corresponding podcast at https://ajpheart.podbean.com/e/maternal-vaping-impairs-vascular-function-in-theoffspring/.
Topics: Acetylcholine; Aerosols; Animals; E-Cigarette Vapor; Electronic Nicotine Delivery Systems; Endothelium, Vascular; Female; Middle Cerebral Artery; Nicotine; Nicotinic Agonists; Nitroprusside; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Serotonin; Vaping; Vasoconstriction; Vasoconstrictor Agents; Vasodilation; Vasodilator Agents
PubMed: 34170194
DOI: 10.1152/ajpheart.00206.2021 -
Journal of Applied Physiology... Jan 2021This study investigated the hypothesis that β-adrenoreceptor-mediated inhibition of sympathetic vasoconstriction would be enhanced in female compared with male rats,...
This study investigated the hypothesis that β-adrenoreceptor-mediated inhibition of sympathetic vasoconstriction would be enhanced in female compared with male rats, and that endurance exercise training would augment β-adrenoreceptor-mediated inhibition of sympathetic vasoconstriction in male and female rats. Sprague-Dawley rats were randomized into sedentary (male: = 7; female: = 8) and exercise-trained (male: = 9; female: = 9) groups. Following 4 wk of exercise training or being sedentary, rats were anesthetized and surgically instrumented for stimulation of the lumbar sympathetic chain, muscle contraction and measurement of arterial blood pressure and femoral artery blood flow (FBF). Femoral vascular conductance (FVC) was calculated as FBF/mean arterial pressure. The percentage change of FVC in response to sympathetic stimulation delivered at 2 and 5 Hz was measured at rest and during contraction of the triceps surae muscles before and after β-adrenoreceptor blockade (propranolol: 0.075 mg·kg iv). We found that, at rest, β-adrenoreceptor blockade decreased (main effect of drug, 2 Hz: < 0.001; 5 Hz: < 0.001) sympathetic vasoconstriction. During contraction, sympathetic vasoconstrictor responsiveness was lower (main effect of sex, 2 Hz: = 0.001; 5 Hz: = 0.023) in female compared with male rats, and sympatholysis was enhanced (main effect of sex, 2 Hz: = 0.001; 5 Hz: < 0.001) in female rats. β-adrenoreceptor blockade decreased (main effect of drug, 2 Hz: = 0.049; 5 Hz: < 0.001) evoked sympathetic vasoconstriction in contracting muscle. The present study demonstrated that β-adrenoreceptors do not blunt sympathetic vasoconstriction in resting or contracting skeletal muscle of male or female rats. Sympatholysis was enhanced in female rats; however, this was not attributable to β-adrenoreceptor-mediated blunting of sympathetic vasoconstriction. β-adrenoreceptors do not inhibit sympathetic vasoconstriction in resting or contracting muscle of male or female rats, regardless of training status. Sympatholysis was enhanced in female, compared to male rats; however, β-adrenoreceptors were not responsible for the enhanced sympatholysis. These findings indicate that β-adrenoreceptors do not contribute to the regulation of sympathetic vasoconstriction in resting and contracting skeletal muscle and suggest that β-adrenoreceptors do not underlie sex differences in the neural control of the circulation.
Topics: Animals; Female; Male; Muscle Contraction; Muscle, Skeletal; Rats; Rats, Sprague-Dawley; Regional Blood Flow; Sympathetic Nervous System; Vasoconstriction
PubMed: 33090912
DOI: 10.1152/japplphysiol.00726.2020 -
Scientific Reports Jul 2018Auricular vasomotor responses are considered to be signs of clinical conditions including migraine. The mechanisms of auricular vasomotor control are still debatable....
Auricular vasomotor responses are considered to be signs of clinical conditions including migraine. The mechanisms of auricular vasomotor control are still debatable. This study aimed at investigating perivascular co-transmitters of vasomotor control in the auricle. Another aim was to provide three-dimensional arterial maps of the auricle, as a proxy of periarterial autonomic innervation. Twelve paired human auricles were used to visualize the arteries following Spalteholz clearing and μ-CT-based reconstruction. Perivascular innervation staining was conducted using anti-tyrosine hydroxylase (TH), anti-neuropeptide Y (NPY), anti-vasoactive intestinal peptide (VIP) and anti-choline acetyl transferase (ChAT). The combined Spalteholz technique and μ-CT revealed a highly consistent arrangement of the auricular vasculature. The superficial temporal (STA) and posterior auricular artery (PAA) supply the helical rim arcade and arcade, with the STA mainly forming the superior and the PAA forming the middle and inferior auricular artery. Co-existence of sympathetic NPY+ and TH+ terminals mediating vasoconstriction, and VIP+ and ACh+ indicating cholinergic vasodilatation, was found in the perivascular zone. The presence of both sympathetic vasoconstriction and cholinergic co-innervation for active vasodilatation was shown in the perivascular auricular zone. Assuming that the highly-consistent vasculature gives way to these terminals, this periarterial innervation may be found spread out across the helix.
Topics: Aged, 80 and over; Arteries; Autonomic Nervous System; Ear Auricle; Female; Humans; Male; Neuropeptide Y; Tyrosine 3-Monooxygenase; Vasoactive Intestinal Peptide; Vasoconstriction; Vasodilation
PubMed: 30065349
DOI: 10.1038/s41598-018-29839-z -
The Journal of Physiology Jan 2023
Topics: Humans; Vasoconstriction; Hypoxia
PubMed: 36524431
DOI: 10.1113/JP284057 -
The Journal of Physiological Sciences :... Jan 2015It is well known that ovarian function is regulated by hypothalamic-pituitary-ovarian hormones. However, although several histological studies have described the... (Review)
Review
It is well known that ovarian function is regulated by hypothalamic-pituitary-ovarian hormones. However, although several histological studies have described the autonomic innervation of the ovary, the involvement of these autonomic nerves in ovarian function is unclear. Recently, it has been shown that both the superior ovarian nerve (SON) and the ovarian nerve plexus (ONP) induce vasoconstrictor activity by activation of alpha 1-adrenoceptors, whereas the SON, but not the ONP, inhibits ovarian estradiol secretion by activation of alpha 2-adrenoceptors. Furthermore, reflex activation of these ovarian nerves by noxious cutaneous stimulation of the rat hindpaw results in ovarian vasoconstriction and inhibition of estradiol secretion. Thus, in addition to long-term regulation of ovarian function by hormones, ovarian autonomic innervation may be involved in rapid regulation of ovarian function by responding to either internal or external environmental changes.
Topics: Afferent Pathways; Animals; Autonomic Pathways; Electric Stimulation; Estradiol; Female; Ovary; Physical Stimulation; Rats; Regional Blood Flow; Sympathetic Nervous System; Vasoconstriction
PubMed: 24966153
DOI: 10.1007/s12576-014-0324-9 -
Advances in Pharmacology (San Diego,... 2017Potassium channels importantly contribute to the regulation of vascular smooth muscle (VSM) contraction and growth. They are the dominant ion conductance of the VSM cell... (Review)
Review
Potassium channels importantly contribute to the regulation of vascular smooth muscle (VSM) contraction and growth. They are the dominant ion conductance of the VSM cell membrane and importantly determine and regulate membrane potential. Membrane potential, in turn, regulates the open-state probability of voltage-gated Ca channels (VGCC), Ca influx through VGCC, intracellular Ca, and VSM contraction. Membrane potential also affects release of Ca from internal stores and the Ca sensitivity of the contractile machinery such that K channels participate in all aspects of regulation of VSM contraction. Potassium channels also regulate proliferation of VSM cells through membrane potential-dependent and membrane potential-independent mechanisms. VSM cells express multiple isoforms of at least five classes of K channels that contribute to the regulation of contraction and cell proliferation (growth). This review will examine the structure, expression, and function of large conductance, Ca-activated K (BK) channels, intermediate-conductance Ca-activated K (K3.1) channels, multiple isoforms of voltage-gated K (K) channels, ATP-sensitive K (K) channels, and inward-rectifier K (K) channels in both contractile and proliferating VSM cells.
Topics: Animals; Humans; Membrane Potentials; Muscle, Smooth, Vascular; Potassium Channels; Vasoconstriction
PubMed: 28212804
DOI: 10.1016/bs.apha.2016.07.001 -
Cells Jul 2022In intrapulmonary arteries (IPAs), mechanical forces due to blood flow control vessel tone, and these forces change during pulmonary hypertension (PH). Piezo1, a...
In intrapulmonary arteries (IPAs), mechanical forces due to blood flow control vessel tone, and these forces change during pulmonary hypertension (PH). Piezo1, a stretch-activated calcium channel, is a sensor of mechanical stress present in both endothelial cells (ECs) and smooth muscle cells (SMCs). The present study investigated the role of Piezo1 on IPA in the chronic hypoxia model of PH. Rats were raised in chronically hypoxic conditions for 1 (1W-CH, early stage) or 3 weeks (3W-CH, late-stage) of PH or in normoxic conditions (Nx). Immunofluorescence labeling and patch-clamping revealed the presence of Piezo1 in both ECs and SMCs. The Piezo1 agonist, Yoda1, induced an IPA contraction in Nx and 3W-CH. Conversely, Yoda1 induced an endothelial nitric oxide (eNOS) dependent relaxation in 1W-CH. In ECs, the Yoda1-mediated intracellular calcium concentration ([Ca]i) increase was greater in 1W-CH as compared to Nx. Yoda1 induced an EC hyperpolarization in 1W-CH. The eNOS levels were increased in 1W-CH IPA compared to Nx or 3W-CH PH and Yoda1 activated phosphorylation of Akt (Ser473) and eNOS (Ser1177). Thus, we demonstrated that endothelial Piezo1 contributes to intrapulmonary vascular relaxation by controlling endothelial [Ca]i, endothelial-dependent hyperpolarization, and Akt-eNOS pathway activation in the early stage of PH.
Topics: Animals; Endothelial Cells; Hypertension, Pulmonary; Hypoxia; Nitric Oxide; Proto-Oncogene Proteins c-akt; Pulmonary Artery; Rats; Vasoconstriction
PubMed: 35954193
DOI: 10.3390/cells11152349