Estrogen regulates myogenic tone in pressurized cerebral arteries by enhanced basal release of nitric oxide

1997 ◽  
Vol 273 (5) ◽  
pp. H2248-H2256 ◽  
Author(s):  
Peter Skarsgard ◽  
Cornelis Van Breemen ◽  
Ismail Laher
Keyword(s):  
Nitric Oxide ◽  
Cerebral Arteries ◽  
Calcium Ionophore ◽  
Myogenic Tone ◽  
Sprague Dawley ◽  
No Donor ◽  
Sprague Dawley Rats ◽  
Middle Cerebral Arteries ◽  
Basal Release ◽  
Endogenous Estrogen

Second-order middle cerebral arteries (135.0 ± 4.6 μm ID) from male, female, ovariectomized female (no endogenous estrogen), and estrogen-treated ovariectomized female Sprague-Dawley rats were harvested and mounted in a pressure myograph. Myogenic response was recorded over a pressure range of 10–100 mmHg and was repeated in the presence of N ω-nitro-l-arginine methyl ester (l-NAME; 2 × 10−4 M), an inhibitor of nitric oxide (NO) synthase, and after endothelium removal, to examine the contribution of NO to net myogenic tone. With intact endothelium, there were no differences in myogenic tone between the groups, but in the presence of l-NAME and after endothelium removal, estrogen-exposed vessels developed significantly greater tone at high transmural pressure. There were no differences in sensitivity to sodium nitroprusside, an NO donor, or A-23187, a calcium ionophore. These results suggest an increase in basal release of NO in cerebral arteries exposed to estrogen, without change in NO sensitivity or maximally stimulated NO release.

Abstract 357: Cerebral Arterial Endothelial Dysfunction in the Post-Cardiac Arrest Period

Circulation ◽  
2019 ◽  
Vol 140 (Suppl_2) ◽  
Author(s):  
Frederik B Hansen ◽  
Goncalo Esteves ◽  
Niels Secher ◽  
Bo Lofgren ◽  
Ulf Simonsen ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Endothelial Dysfunction ◽  
Cerebral Arteries ◽  
Channel Blockers ◽  
Sprague Dawley ◽  
No Donor ◽  
Sprague Dawley Rats ◽  
Middle Cerebral Arteries ◽  
Cerebral Vasodilation ◽  
Synthase Inhibitor

Introduction: Cardiac arrest (CA) has a poor prognosis due to brain injury that progresses over time. Endothelial dysfunction may play an important role in the impairment of the cerebral circulation after CA. Aims: To investigate 1) whether endothelial dysfunction is present in cerebral arteries, and 2) if the altered endothelial function is caused by increased activity of calcium-activated potassium (K ca ) channels. Methods: Male Sprague-Dawley rats (403g±24g) were anaesthetized, intubated and ventilated. Four groups were examined; two CA groups observed for either 2 hours (2h-CA, n=10) or 4 hours (4h-CA, n=10) and two corresponding sham groups (2h-sham, n=10; 4h-sham, n=10). Following 7 minutes of asphyxial CA, the rats were resuscitated using adrenaline, ventilation, and chest compressions. Middle cerebral arteries were isolated and examined in wire-myographs. Results: Cerebral vasodilation was significantly enhanced in response to bradykinin in arteries from 4h-CA rats when compared to 4h-sham rats (4h-sham: E max 58% (5.57 of 9.69) ± 6% vs 4h-CA: E max 84% (6.16 of 7.32) ± 4%, p=0.007). Likewise, vasodilation induced by NS309 (K Ca -channel activator) was increased in CA rats when compared to sham rats. In the presence of L-NAME (NO synthase inhibitor), bradykinin induced vasodilation was significantly augmented in 4h-CA rats when compared to 4h-sham rats, whereas SNP (NO donor) induced vasodilation was similar between groups. In the presence of L-NAME and K Ca -channel blockers (UCL1684 and ICA-17043), bradykinin induced vasodilation was abolished in cerebral arteries in all four groups. Conclusion: Our findings demonstrate an enhanced endothelial-dependent vasodilation in cerebral arteries in the post-cardiac arrest period. The increased vasodilatory response may be explained by increased endothelial K Ca -channel activity and bioavailability of NO, and may contribute to dysregulation of cerebral blood flow after CA.

Permissive role of NO in alpha 2-adrenoceptor-mediated dilations in rat cerebral arteries

1995 ◽  
Vol 269 (3) ◽  
pp. H1171-H1174 ◽  
Author(s):  
R. M. Bryan ◽  
M. L. Steenberg ◽  
M. Y. Eichler ◽  
T. D. Johnson ◽  
M. W. Swafford ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cerebral Arteries ◽  
No Donor ◽  
Cyclic Monophosphate ◽  
Adrenoceptor Agonist ◽  
Middle Cerebral Arteries ◽  
Basal Release ◽  
Oxide Synthase ◽  
Permissive Role

Dilations produced with UK-14304, a selective alpha 2-adrenoceptor agonist, in rat middle cerebral arteries (MCAs) were blocked after removal of the endothelium or inhibition of nitric oxide synthase (NOS). After endothelium removal or inhibition of NOS, the addition of subthreshold doses of an exogenous nitric oxide (NO) donor, S-nitroso-N-acetylpenicillamine, restored the dilations produced by UK-14304. In a similar manner the guanosine 3',5'-cyclic monophosphate (cGMP) analogues 8-bromoguanosine 3',5'-cyclic monophosphate and N2,2'-O-dibutyrylguanosine 3',5'-cyclic monophosphate restored the dilations of MCAs after endothelial removal. Because NO cannot be synthesized and released in MCAs after inhibition of NOS, it cannot be directly responsible for the dilation. The basal release of NO from the endothelium acts permissively in the vasodilation by maintaining adequate levels of cGMP. Removal of this basal release of NO by removal of endothelium or inhibition of NOS abolishes the alpha 2-adrenoceptor-mediated dilation.

Abstract P607: Nitric Oxide (NO) Regulates Paracellular Permselectivity in Isolated, Perfused Rat Thick Ascending Limbs through Claudin-19

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Casandra M Monzon ◽  
Jeffrey Garvin
Keyword(s):  
Nitric Oxide ◽  
Control Period ◽  
Sprague Dawley ◽  
Permeability Ratio ◽  
Ionic Selectivity ◽  
No Donor ◽  
Sprague Dawley Rats ◽  
Spermine Nonoate ◽  
Dilution Potential ◽  
Cl Permeability

About 50% of the Na reabsorbed in thick ascending limbs (TALs) traverses the paracellular pathway. The ionic selectivity of this route is regulated by claudins in the tight junctions. TALs express claudin-19 which has been reported to regulate TAL Na permeability. We showed that nitric oxide (NO) decreases Na/Cl permeability ratio (PNa/PCl) in TALs by increasing the absolute permeabilities of both ions though PCl increased more. However, whether NO affects paracellular permeability via claudin-19 is unknown. We hypothesize that NO regulates the paracellular permselectivity in TALs through this claudin. To test this we perfused TALs from Sprague Dawley rats and measured dilution potentials (a measure of permselectivity) with and without exogenously-added or endogenously-produced NO in the presence or absence of an antibody against an extracellular domain of claudin-19 or Tamm-Horsfall protein (control). Dilution potentials were generated by reducing bath NaCl from 141 to 32 mM. For the NO donor spermine NONOate (SPM): during the control period, the dilution potential was -9.3 ± 1.8 mV. After SPM (200 μM), it was -6.7 ± 1.6 mV (n = 6; p < 0.003). In the presence of the claudin-19 antibody, SPM had no significant effect on dilution potentials (claudin-19 antibody alone: -12.7 ± 2.1 mV vs claudin-19 antibody + SPM: -12.9 ± 2.4 mV; n = 6). The claudin-19 antibody alone had no effect on dilution potentials. In the presence of the Tamm-Horsfall protein, the effect of SPM was still present (Tamm-Horsfall protein antibody alone: -9.7 ± 1.0 mV; Tamm-Horsfall protein antibody + SPM: -6.3 ± 1.1 mV, p<0.006, n = 6). For experiments with endogenously-produced NO, L-arginine the substrate for NO synthase was added. During the control period, the dilution potential was -11.0 ± 1.1 mV. After L-arginine (500 μM) treatment, they were -9.0 ± 1.2 mV (n = 9; p < 0.05). In the presence of the claudin-19 antibody, L-arginine had no significant effect on dilution potentials (claudin-19 antibody alone: -10.1 ± 0.9 mV vs claudin-19 antibody + L-arginine: -10.1 ± 1.0 mV; n = 9). In the presence of the Tamm-Horsfall protein, the effect of L-arginine was still present. We conclude that the actions of NO on the paracellular permselectivity in thick ascending limbs are at least in part mediated by claudin-19.

Cerebral artery reactivity changes during pregnancy and the postpartum period: a role in eclampsia?

2004 ◽  
Vol 286 (6) ◽  
pp. H2127-H2132 ◽  
Author(s):  
Marilyn J. Cipolla ◽  
Lisa Vitullo ◽  
John McKinnon
Keyword(s):  
Cerebral Artery ◽  
Postpartum Period ◽  
Cerebral Arteries ◽  
Hypertensive Encephalopathy ◽  
Myogenic Tone ◽  
No Production ◽  
Sprague Dawley ◽  
Cerebrovascular Resistance ◽  
Sprague Dawley Rats ◽  
Myogenic Activity

Eclampsia is thought to be similar to hypertensive encephalopathy, whereby acute elevations in intravascular pressure cause forced dilatation (FD) of intrinsic myogenic tone of cerebral arteries and arterioles, decreased cerebrovascular resistance, and hyperperfusion. In the present study, we tested the hypothesis that pregnancy and/or the postpartum period predispose cerebral arteries to FD by diminishing pressure-induced myogenic activity. We compared the reactivity to pressure (myogenic activity) as well as factors that modulate the level of tone of third-order branches (<200 μm) of the posterior cerebral artery (PCA) that were isolated from nonpregnant (NP, n = 7), late-pregnant (LP, 19 days, n = 10), and postpartum (PP, 3 days, n = 8) Sprague-Dawley rats under pressurized conditions. PCAs from all groups of animals developed spontaneous tone within the myogenic pressure range (50–150 mmHg) and constricted arteries at 100 mmHg (NP, 30 ± 3; LP, 39 ± 4; and PP, 42 ± 7%; P > 0.05). This level of myogenic activity was maintained in the NP arteries at all pressures; however, both LP and PP arteries dilated at considerably lower pressures compared with NP, which lowered the pressure at which FD occurred from >175 for NP to 146 ± 6.5 mmHg for LP ( P < 0.01 vs. NP) and 162 ± 7.7 mmHg for PP ( P < 0.01 vs. NP). The amount of myogenic tone was also significantly diminished at 175 mmHg compared with NP: percent tone for NP, LP, and PP animals were 35 ± 2, 11 ± 3 ( P < 0.01 vs. NP), and 20 ± 7% ( P < 0.01 vs. NP), respectively. Inhibition of nitric oxide (NO) with 0.1 mM Nω-nitro-l-arginine (l-NNA) caused constriction of all vessel types that was significantly increased in the PP arteries, which demonstrates significant basal NO production. Reactivity to 5-hydroxytryptamine (serotonin) was assessed in the presence of l-NNA and indomethacin. There was a differential response to serotonin: PCAs from NP animals dilated, whereas LP and PP arteries constricted. These results suggest that both pregnancy and the postpartum period predispose the cerebral circulation to FD at lower pressures, a response that may lower cerebrovascular resistance and promote hyperperfusion when blood pressure is elevated, as occurs during eclampsia.

Cgmp-Dependent Calcium Desensitization Contributes to Vasodilator Response to Nitric Oxide in Rat Middle Cerebral Arteries

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 719-719
Author(s):  
Cheng-wen Sun ◽  
David R Harder ◽  
Richard J Roman
Keyword(s):  
Nitric Oxide ◽  
Guanylyl Cyclase ◽  
Cerebral Arteries ◽  
No Donor ◽  
Vasodilator Response ◽  
Calcium Desensitization ◽  
Vasoconstrictor Response ◽  
Middle Cerebral Arteries ◽  
Dependent Component ◽  
Dependent Mechanism

P142 We have recently reported that a cGMP-dependent mechanism as well as a cGMP-independent activation of K Ca channels secondary to a fall in 20-HETE contributes to the vasodilator response to NO in the cerebral circulation. The present study examines the mechanism for the cGMP-dependent component of the vasodilator response to NO in rat middle cerebral arteries (MCA). Administration of a NO donor, dose-dependently, increased the diameter of serotonin preconstricted MCA to 69.3±5.8% of control (n=6). 8-Br-cGMP (10 -8 to 10 -4 M) mimicked the effect of NO and increased the diameter of MCA to 58.7±3.6% of control (n=6). Blockade of K Ca channels with IBTX (10 -7 M, n=6) or depolarization with a 80 mM K + media (n=6)reduced the vasodilator response of MCA to NO by 70±6%, but they had little effect on the vasodilator response to 8-Br-cGMP. This suggests that activation of K + channels contribute to the vasodilator response to NO in MCA, but not the response to 8-Br-cGMP. We therefore examined the effects of NO and cGMP on Ca 2+ -induced contraction of rat MCAs permeablized with α-toxin (10 μg/ml) and ionomycin (10 μM). Elevations in bath Ca 2+ , from 10 -8 to 10 -5 M, decreased the diameter of these vessels by 60.9±3.7%. A NO donor, DEA-NONOate (10 -6 M, n=6)and 8-Br-cGMP (10 -4 M, n=6) both attenuated the vasoconstrictor response to elevations in bath Ca 2+ by 60%. Inhibition of guanylyl cyclase with ODQ (10 -5 M) prevented the effects of the NO donor, but not 8-Br-cGMP. These results indicate that the cGMP, PKG-dependent component of the vasodilator response of NO in rat MCA is mediated by desensitization of the contractile mechanism to calcium rather than activation of K + channels.

scholarly journals Angiogenesis after Stroke is Correlated with Increased Numbers of Macrophages: The Clean-up Hypothesis

2001 ◽  
Vol 21 (10) ◽  
pp. 1223-1231 ◽  
Author(s):  
Panya S. Manoonkitiwongsa ◽  
Catherine Jackson-Friedman ◽  
Paul J. McMillan ◽  
Robert L. Schultz ◽  
Patrick D. Lyden
Keyword(s):  
Microvessel Density ◽  
Focal Cerebral Ischemia ◽  
Cerebral Arteries ◽  
Sprague Dawley ◽  
Regional Cerebral Blood ◽  
Ischemic Brain ◽  
Sprague Dawley Rats ◽  
Middle Cerebral Arteries ◽  
The Brain ◽  
Left Middle

Brain cells manufacture and secrete angiogenic peptides after focal cerebral ischemia, but the purpose of this angiogenic response is unknown. Because the maximum possible regional cerebral blood flow is determined by the quantity of microvessels in each unit volume, it is possible that angiogenic peptides are secreted to generate new collateral channels; other possibilities include neuroprotection, recovery/regeneration, and removal of necrotic debris. If the brain attempts to create new collaterals, microvessel density should increase significantly after ischemia. Conversely, if angiogenic-signaling molecules serve some other purpose, microvessel densities may increase slightly or not at all. To clarify, the authors measured microvessel densities with quantitative morphometry. Left middle cerebral arteries of adult male Sprague–Dawley rats were occluded with intraluminal nylon suture for 4 hours followed by 7, 14, 19, or 30 days of reperfusion. Controls received no surgery or suture occlusion. Changes in microvessel density and macrophage numbers were measured by light microscopic morphometry using semiautomated stereologic methods. Microvessel density increased only in the ischemic margin adjacent to areas of pannecrosis and was always associated with increased numbers of macrophages. Ischemic brain areas without macrophages displayed no vascularity changes compared with normal animals. These data suggest that ischemia-induced microvessels are formed to facilitate macrophage infiltration and removal of necrotic brain.

scholarly journals Effect of Nearby Construction Activity on Endothelial Function, Sensitivity to Nitric Oxide, and Potassium Channel Activity in the Middle Cerebral Arteries of Rats

2020 ◽  
Author(s):  
Maia N Terashvili ◽  
Kaleigh N Kozak ◽  
Debebe Gebremedhin ◽  
Linda A Allen ◽  
Alison L Gifford ◽  
...  
Keyword(s):  
Single Channel ◽  
Cerebral Arteries ◽  
High Sensitivity ◽  
Vibration Monitoring ◽  
Raspberry Pi ◽  
Sprague Dawley ◽  
Film Sensor ◽  
No Donor ◽  
Middle Cerebral Arteries ◽  
Construction Activity

The present study assessed the effect of nearby construction activity on the responses of rat middle cerebral arteries (MCA)to the endothelium-dependent vasodilator acetylcholine and the NO donor sodium nitroprusside (SNP) and the activity of MaxiK potassium channels in MCA smooth muscle cells from male Sprague–Dawley rats. Two monitoring systems were used to assess vibrations in the animal rooms during and immediately after construction activities near the research building where the animal facility is located. One was a commercially available system; the other was a Raspberry-Pi (RPi)–based vibration monitoring system designed in our laboratory that included a small computing unit attached to a rolling sensor (low sensitivity) and a piezoelectric film sensor (high sensitivity). Both systems recorded increased levels of vibration during construction activity outside the building. During the construction period, vasodilator responses to acetylcholine and SNP were abolished, and MaxiK single-channel current opening frequency and open-state probability in cell-attached patches of isolated MCA myocytes were dramatically decreased. Recovery of acetylcholine- and SNP-induced dilation was minimal in MCA from rats studied after completion of construction but housed in the animal facility during construction, whereas responses to acetylcholine and SNP were intact in rats purchased, housed, and studied after construction. Baseline levels of vibration returned after the completion of construction, concomitant with the recovery of normal endothelium-dependent vasodilation to acetylcholine and of NO sensitivity assessed by using SNP in MCA from animals obtained after construction. The results of this study indicate that the vibration associated with nearby construction can have highly disruptive effects on crucial physiologic phenotypes.

scholarly journals Exercise training and muscle microvascular oxygenation: functional role of nitric oxide

2012 ◽  
Vol 113 (4) ◽  
pp. 557-565 ◽  
Author(s):  
Daniel M. Hirai ◽  
Steven W. Copp ◽  
Scott K. Ferguson ◽  
Clark T. Holdsworth ◽  
Danielle J. McCullough ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Exercise Training ◽  
Peak Oxygen Uptake ◽  
Sprague Dawley ◽  
No Donor ◽  
Phosphorescence Quenching ◽  
Metabolic Adaptations ◽  
Sprague Dawley Rats ◽  
Microvascular Oxygenation

Exercise training induces multiple adaptations within skeletal muscle that may improve local O2delivery-utilization matching (i.e., Po2mv). We tested the hypothesis that increased nitric oxide (NO) function is intrinsic to improved muscle Po2mv kinetics from rest to contractions after exercise training. Healthy young Sprague-Dawley rats were assigned to sedentary ( n = 18) or progressive treadmill exercise training ( n = 10; 5 days/wk, 6–8 wk, final workload of 60 min/day at 35 m/min, −14% grade) groups. Po2mv was measured via phosphorescence quenching in the spinotrapezius muscle at rest and during 1-Hz twitch contractions under control (Krebs-Henseleit solution), sodium nitroprusside (SNP, NO donor; 300 μM), and NG-nitro-l-arginine methyl ester (l-NAME, nonspecific NO synthase blockade; 1.5 mM) superfusion conditions. Exercise-trained rats had greater peak oxygen uptake (V̇o2peak) than their sedentary counterparts (81 ± 1 vs. 72 ± 2 ml·kg−1·min−1, respectively; P < 0.05). Exercise-trained rats had significantly slower Po2mv fall throughout contractions (τ1; time constant for the first component) during control (sedentary: 8.1 ± 0.6; trained: 15.2 ± 2.8 s). Compared with control, SNP slowed τ1to a greater extent in sedentary rats (sedentary: 38.7 ± 5.6; trained: 26.8 ± 4.1 s; P > 0.05) whereas l-NAME abolished the differences in τ1between sedentary and trained rats (sedentary: 12.0 ± 1.7; trained: 11.2 ± 1.4 s; P < 0.05). Our results indicate that endurance exercise training leads to greater muscle microvascular oxygenation across the metabolic transient following the onset of contractions (i.e., slower Po2mv kinetics) partly via increased NO-mediated function, which likely constitutes an important mechanism for training-induced metabolic adaptations.

Sign in / Sign up

Export Citation Format

Share Document