scholarly journals Relaxin induces rapid, transient vasodilation in the microcirculation of hamster skeletal muscle

2013 ◽  
Vol 218 (2) ◽  
pp. 179-191 ◽  
Author(s):  
Jordan M Willcox ◽  
Alastair J S Summerlee ◽  
Coral L Murrant
Keyword(s):  
Skeletal Muscle ◽  
Gap Junction ◽  
Fourth Order ◽  
Peripheral Resistance ◽  
Second Order ◽  
Systemic Resistance ◽  
Transient Nature ◽  
Channel Dependent ◽  
Synthase Inhibitor

Relaxin produces a sustained decrease in total peripheral resistance, but the effects of relaxin on skeletal muscle arterioles, an important contributor to systemic resistance, are unknown. Using the intact, blood-perfused hamster cremaster muscle preparationin situ, we tested the effects of relaxin on skeletal muscle arteriolar microvasculature by applying 10−10 M relaxin to second-, third- and fourth-order arterioles and capillaries. The mechanisms responsible for relaxin-induced dilations were explored by applying 10−10 M relaxin to second-order arterioles in the presence of 10−5 M N(G)-nitro-l-arginine methyl ester (l-NAME, nitric oxide (NO) synthase inhibitor), 10−5 M glibenclamide (GLIB, ATP-dependent potassium (K+) channel inhibitor), 10−3 M tetraethylammonium (TEA) or 10−7 M iberiotoxin (IBTX, calcium-associated K+channel inhibitor). Relaxin caused second- (peak change in diameter: 8.3±1.7 μm) and third (4.5±1.1 μm)-order arterioles to vasodilate transiently while fourth-order arterioles did not (0.01±0.04 μm). Relaxin-induced vasodilations were significantly inhibited byl-NAME, GLIB, TEA and IBTX. Relaxin stimulated capillaries to induce a vasodilation in upstream fourth-order arterioles (2.1±0.3 μm), indicating that relaxin can induce conducted responses vasodilation that travels through blood vessel walls via gap junctions. We confirmed gap junction involvement by showing that gap junction uncouplers (18-β-glycyrrhetinic acid (40×10−6 M) or 0.07% halothane) inhibited upstream vasodilations to localised relaxin stimulation of second-order arterioles. Therefore, relaxin produces transient NO- and K+channel-dependent vasodilations in skeletal muscle arterioles and stimulates capillaries to initiate conducted responses. The transient nature of the arteriolar dilation brings into question the role of skeletal muscle vascular beds in generating the sustained systemic haemodynamic effects induced by relaxin.

Nitric oxide activity in the peripheral vasculature during normotensive and preeclamptic pregnancy

1999 ◽  
Vol 277 (2) ◽  
pp. H848-H854 ◽  
Author(s):  
Dilly O. C. Anumba ◽  
Stephen C. Robson ◽  
Richard J. Boys ◽  
Gary A. Ford
Keyword(s):  
Nitric Oxide ◽  
Forearm Blood Flow ◽  
Peripheral Resistance ◽  
Normal Pregnancy ◽  
Ang Ii ◽  
Third Trimester ◽  
Peripheral Vasculature ◽  
Infusion Of Norepinephrine ◽  
Synthase Inhibitor

We investigated the role of nitric oxide (NO) in the vascular resistance changes of normotensive and preeclamptic pregnancy. Forearm blood flow (FBF) responses to brachial artery infusion of N G-monomethyl-l-arginine (l-NMMA), an NO synthase inhibitor, and angiotensin II (ANG II), an NO-independent vasoconstrictor, were determined by plethysmography in 20 nonpregnant women, 20 normotensive primigravidae, and 15 primigravidae with untreated preeclampsia. In pregnant subjects, FBF was reduced to nonpregnancy levels by infusion of norepinephrine (NE), which was then coinfused with ANG II (2, 4, and 8 ng/min) and l-NMMA (200, 400, and 800 μg/min) each for 5 min. In separate studies, responses to NE (20, 50, and 100 ng/min) were determined in 8 nonpregnant women, with FBF elevated to pregnancy levels by concomitant infusion of glyceryl trinitrate, and 10 pregnant women. Vasoconstrictor responses tol-NMMA were increased in pregnant compared with nonpregnant subjects [mean ± SE summary measure (in arbitrary units): 60 ± 7 vs. 89 ± 8, respectively; P < 0.01], whereas responses to ANG II were blunted (125 ± 11 vs. 79 ± 7, respectively; P < 0.001). Compared with normotensive pregnant subjects, preeclamptic subjects had an enhanced response to ANG II (79 ± 7 vs. 103 ± 8, respectively; P < 0.05) but no difference in response to l-NMMA (89 ± 8 vs. 73 ± 10, respectively; P = 0.30). Responses to NE were similar in pregnant and nonpregnant subjects (110 ± 20 vs. 95 ± 33, respectively; P = 0.66). During the third trimester of pregnancy, forearm constrictor responses tol-NMMA are increased. The responses to NE are unchanged, whereas responses to ANG II are blunted. Increased NO activity contributes to the fall in peripheral resistance. In preeclampsia, forearm constrictor responses to ANG II but notl-NMMA are increased compared with those in normal pregnancy. Changes in vascular NO activity are unlikely to account for the increased vascular tone in this condition.

Enhanced response of arterioles to oxygen during development of hypertension in SHR

1986 ◽  
Vol 250 (5) ◽  
pp. H761-H764 ◽  
Author(s):  
J. H. Lombard ◽  
M. E. Hess ◽  
W. J. Stekiel
Keyword(s):  
Skeletal Muscle ◽  
Vascular Resistance ◽  
Local Control ◽  
Fourth Order ◽  
Spontaneously Hypertensive Rat ◽  
Control Mechanisms ◽  
Cremaster Muscle ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto

The goal of this study was to assess the possible role of O2-related local control mechanisms in contributing to an elevated skeletal muscle resistance during the development of hypertension in the spontaneously hypertensive rat (SHR). Diameters of first- (1A), second- (2A), third- (3A), and fourth-order (4A) arterioles were measured by television microscopy in the cremaster muscle of SHR in the early (4- to 6-wk-old) and rapidly developing (8- to 9-wk-old) stages of hypertension and in age-matched normotensive Wistar-Kyoto (WKY) controls. Active neurogenic tone was blocked by superfusing the tissue with 0.1 microgram/ml tetrodotoxin. When superfusion solution PO2 was elevated by changing the gas equilibration mixture from 0 to 5% O2, neurally blocked 3A and 4A of SHR exhibited a significantly greater constriction and a higher incidence of complete closure than those of their age-matched WKY controls. However, there were no significant differences in the constriction of larger arterioles (1A and 2A) in response to elevated superfusion solution PO2. The results suggest that O2-related local control mechanisms could contribute to constriction and closure of small arterioles and to an elevated skeletal muscle vascular resistance early in the development of hypertension in SHR

Vascular adaptations to pregnancy in mice: effects on myogenic tone

2002 ◽  
Vol 283 (6) ◽  
pp. H2226-H2233 ◽  
Author(s):  
Sukrutha Veerareddy ◽  
Christy-Lynn M. Cooke ◽  
Philip N. Baker ◽  
Sandra T. Davidge
Keyword(s):  
Gap Junction ◽  
Myogenic Tone ◽  
Internal Diameter ◽  
Uterine Arteries ◽  
The Difference ◽  
Prostaglandin H ◽  
Synthase Inhibitor ◽  
Gap Junction Inhibitor ◽  
In Pregnancy

The mechanisms underlying vascular adaptations in pregnancy remain to be fully elucidated. One of the contributory mechanisms for reduced vascular tone may be a reduction of myogenic tone. Myogenic tone was assessed as the difference between internal diameter in the presence and absence of external calcium at different intramural pressure steps (60–100 mmHg). Myogenic responses were reduced in resistance-sized mesenteric and main uterine arteries in late pregnant compared with nonpregnant C57BL/6J mice. In vessels from pregnant, but not nonpregnant mice, the myogenic response was enhanced by preincubation with nitric oxide (NO) synthase inhibitor N G-nitro-l-arginine methyl ester, was further elevated by the gap junction inhibitor 18-α glycyrrhetinic acid, but was unaltered by the prostaglandin H synthase inhibitor meclofenamate. Endothelium removal enhanced myogenic tone only in the vessels from pregnant animals, thus confirming the role of the endothelium in modulating myogenic tone in pregnancy. These results suggest that endothelium-derived NO as well as gap junction communications modulate myogenic tone in mouse pregnancy.

Role of carotid and aortic bodies in mediating the increase in cardiac output during anoxemia

1962 ◽  
Vol 203 (1) ◽  
pp. 133-136 ◽  
Author(s):  
Mario Penna ◽  
Lawrence Soma ◽  
Domingo M. Aviado
Keyword(s):  
Cardiac Output ◽  
Venous Return ◽  
Control Level ◽  
Peripheral Resistance ◽  
Systemic Resistance ◽  
Dilution Technique ◽  
Similar Reduction ◽  
Anesthetized Dogs ◽  
Possible Cause

In 14 anesthetized dogs the inhalation of 5% oxygen in nitrogen for 2.5 min caused an increase in cardiac output, measured by the dye dilution technique (16.8% ±6.1 se). After surgical carotid-aortic chemoreceptor denervation, anoxemia still increased cardiac output (27.1% ±6.7 se). An effect of chemoreceptor denervation was the reduction of the control level of cardiac output. In the presence of a similar reduction of cardiac output by bleeding (innervated animal) anoxemia caused a greater increase in cardiac output than in the control preparation. The increase in cardiac output was accompanied by a decrease in total peripheral systemic resistance in the denervated state as compared to an increase in the innervated state. The increase in cardiac output during anoxemia was not prevented by complete spinal anesthesia. A possible cause for the increase in the denervated animal is a combination of the increase in venous return and fall in total systemic peripheral resistance.

scholarly journals Hyperosmolality dilates rat skeletal muscle arterioles: role of endothelial KATP channels and daily exercise

2000 ◽  
Vol 89 (6) ◽  
pp. 2227-2234 ◽  
Author(s):  
Michael P. Massett ◽  
Akos Koller ◽  
Gabor Kaley
Keyword(s):  
Skeletal Muscle ◽  
Katp Channels ◽  
Vessel Diameter ◽  
Cyclooxygenase Inhibitor ◽  
Rat Skeletal Muscle ◽  
Nitric Oxide Synthase Inhibitor ◽  
Daily Exercise ◽  
Synthase Inhibitor ◽  
Oxide Synthase

The purpose of this study was to investigate the mechanism underlying arteriolar responses to hyperosmolality and to determine the effects of daily exercise on this response. Dilator responses were measured in isolated, cannulated, and pressurized skeletal muscle arterioles. Osmolality was increased from ∼290 to 330 mosmol/kgH2O by adding glucose, sucrose, or mannitol to the superfusion solution. All three compounds elicited similar changes in vessel diameter, suggesting that this response was due to changes in osmolality. Responses to glucose were abolished by endothelium removal but were not altered in endothelium-intact vessels by superfusion with the nitric oxide synthase inhibitor N ω-nitro-l-arginine or the cyclooxygenase inhibitor indomethacin. In endothelium-intact arterioles, responses to glucose superfusion with the ATP-sensitive potassium (KATP) channel inhibitor glibenclamide; however, intraluminal perfusion with glibenclamide nearly abolished the responses to glucose and mannitol. Intraluminal administration of glucose elicited a significantly greater dilation than extraluminal glucose. The response to intraluminal glucose was also inhibited by intraluminal glibenclamide. Four weeks of daily exercise did not significantly alter the responses to hyperosmolality in gracilis or soleus muscle arterioles. These data demonstrate that physiological increases in intraluminal osmolality dilate rat skeletal muscle arterioles via activation of endothelial KATP channels; however, this endothelium-dependent response is not augmented by daily exercise.

Evidence for a basal release of a cytochrome-related endothelium-derived hyperpolarizing factor in the radial artery in humans

2006 ◽  
Vol 290 (4) ◽  
pp. H1347-H1352 ◽  
Author(s):  
Jeremy Bellien ◽  
Robinson Joannides ◽  
Michele Iacob ◽  
Philippe Arnaud ◽  
Christian Thuillez
Keyword(s):  
Blood Flow ◽  
Radial Artery ◽  
Basal Diameter ◽  
Conduit Artery ◽  
Channel Dependent ◽  
Synthase Inhibitor ◽  
Echo Tracking ◽  
Cytochrome P 450

Whether a cytochrome P-450 (CYP)-related endothelium-derived hyperpolarizing factor (EDHF), acting through calcium-activated potassium (KCa) channels, interacts with nitric oxide (NO) to regulate the basal diameter of human peripheral conduit arteries is unexplored in vivo. Radial artery diameter (echo tracking) and blood flow (Doppler) were measured, after oral aspirin (500 mg), in eight healthy volunteers during local infusion for 8 min of tetraethylammonium chloride (TEA; 9 μmol/min), as KCa channel inhibitor, and fluconazole (0.4 μmol/min), as CYP inhibitor, alone and in combination with NG-monomethyl-l-arginine (l-NMMA; 8 μmol/min), as endothelial NO synthase inhibitor. Endothelium-independent dilatation was assessed by using sodium nitroprusside (SNP). Radial diameter was unaffected by l-NMMA (0.4 ± 0.9%) and fluconazole (−1.6 ± 0.8%) but was decreased by TEA (−5.0 ± 1.0%), l-NMMA + fluconazole (−5.3 ± 0.5%), and l-NMMA + TEA (−9.9 ± 1.3%). These effects are still significant even when the concomitant decreases in blood flow induced by l-NMMA (−24 ± 4%), TEA (−21 ± 3%), l-NMMA + fluconazole (−26 ± 5%), and l-NMMA + TEA (−35 ± 4%) were taken as covariate into analysis. Conversely, fluconazole alone slightly but not significantly increased radial flow (13 ± 6%). l-NMMA alone or with TEA and with fluconazole enhanced radial artery dilatation to SNP, whereas TEA and fluconazole alone did not modify this response. These results confirm in humans the involvement of NO and KCa channels in the regulation of basal conduit artery diameter. Moreover, the synergistic effect of combined inhibition of NO synthesis and CYP on the decrease in radial diameter in the absence of such effect after l-NMMA and fluconazole alone unmasks the role of CYP in this regulation and shows the presence of an interaction between NO and a CYP-related EDHF to maintain peripheral conduit artery diameter in vivo. Furthermore, the higher vasoconstrictor effect of TEA compared with fluconazole suggests that different KCa channel-dependent hyperpolarizing mechanisms could exist in conduit arteries.

Platelet Aggregation in Whole Blood: The Role of Thromboxane A2 and Adenosine Diphosphate

1985 ◽  
Vol 54 (03) ◽  
pp. 612-616 ◽  
Author(s):  
A J Carter ◽  
S Heptinstall
Keyword(s):  
Platelet Aggregation ◽  
Whole Blood ◽  
Adenosine Diphosphate ◽  
Blood Platelet ◽  
Thromboxane B2 ◽  
Lipoxygenase Inhibitor ◽  
Thromboxane Synthase Inhibitor ◽  
Synthase Inhibitor

SummaryThe platelet aggregation that occurred in whole blood in response to several aggregating agents (collagen, arachidonic acid, adenosine diphosphate, adrenaline and thrombin) was measured using an Ultra-Flo 100 Whole Blood Platelet Counter. The amounts of thromboxane B2 produced were measured by radioimmunoassay. The effects of various inhibitors of thromboxane synthesis and the effects of apyrase, an enzyme that destroys adenosine diphosphate, were determined.Platelet aggregation was always accompanied by the production of thromboxane B2, and the amounts produced depended on the nature and concentration of the aggregating agent used. The various inhibitors of thromboxane synthesis - aspirin and flurbiprofen (cyclo-oxygenase inhibitors), BW755C (a cyclo-oxygenase and lipoxygenase inhibitor) and dazoxiben (a selective thromboxane synthase inhibitor) - did not markedly inhibit aggregation. Results obtained using apyrase showed that adenosine diphosphate contributed to the aggregation process, and that its role must be acknowledged when devising means of inhibiting platelet aggregation in vivo.

The role of angiotensin in electrophysiological gap junction remodeling in human atrial fibrillation

2004 ◽  
Vol 52 (S 1) ◽  
Author(s):  
S Dhein ◽  
A Boldt ◽  
J Garbade ◽  
L Polontchouk ◽  
U Wetzel ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Gap Junction ◽  
Human Atrial Fibrillation

MIOPATIA MUSCULAR ESQUELÉTICA INDUZIDA PELA INSUFICIÊNCIA CARDÍACA DE ETIOLOGIA HIPERTENSIVA: PAPEL TERAPÊUTICO DO TREINAMENTO FÍSICO AERÓBIOHYPERTENSIVE HEART FAILURE-INDUCED SKELETAL MUSCLE MYOPATHY: THERAPEUTIC ROLE OF AEROBIC EXERCISE TRAININGRESUMOA insuficiência cardíaca (IC) é a via final comum da maioria das doenças que acometem o coração. Entre os fatores de risco conhecidos, a hipertensão arterial (HA) é a doença mais frequentemente associada à IC. Caracterizada pela intolerância ao exercício, a IC promove disfunção cardíaca e alterações intrínsecas musculares envolvidas na redução da capacidade física. Várias anormalidades do músculo esquelético têm sido descritas em pacientes e animais com IC, incluindo atrofia, fibrose, mudança na composição dos tipos de fibras, rarefação microvascular e reduzida capacidade de oxidação. Por outro lado, o treinamento físico aeróbio (TFA) vem sendo utilizado como uma importante terapia não farmacológica para a prevenção e o tratamento da IC; em parte, por melhorar a função endotelial e a perfusão coronária, diminuir a resistência vascular periférica e induzir o remodelamento das células musculares cardíacas e esqueléticas, levando ao aumento da captação de oxigênio e resistência à fadiga. Os mecanismos e vias de sinalização intracelular envolvidas nas anormali

2020 ◽  
Vol 30 (2) ◽  
pp. 239-247
Author(s):  
Bruno Rocha de Avila Pelozin ◽  
◽  
Larissa Ferreira-Santos ◽  
Luis Felipe Rodrigues ◽  
Edilamar Menezes de Oliveira ◽  
...  
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Aerobic Exercise ◽  
Therapeutic Role ◽  
Insuficiencia Cardiaca
Sign in / Sign up

Export Citation Format

Share Document