Role of neuronal nitric oxide in the inhibition of sympathetic vasoconstriction in resting and contracting skeletal muscle of healthy rats

2013 ◽  
Vol 115 (1) ◽  
pp. 97-106 ◽  
Author(s):  
Nicholas G. Jendzjowsky ◽  
Darren S. DeLorey
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Muscle Contraction ◽  
Triceps Surae ◽  
Sympathetic Stimulation ◽  
Sprague Dawley ◽  
Sympathetic Vasoconstriction ◽  
In Series ◽  
Nnos Inhibition

Isoform-specific nitric oxide (NO) synthase (NOS) contributions to NO-mediated inhibition of sympathetic vasoconstriction in resting and contracting skeletal muscle are incompletely understood. The purpose of the present study was to investigate the role of neuronal NOS (nNOS) in the inhibition of sympathetic vasoconstriction in resting and contracting skeletal muscle of healthy rats. We hypothesized that acute pharmacological inhibition of nNOS would augment sympathetic vasoconstriction in resting and contracting skeletal muscle, demonstrating that nNOS is primarily responsible for NO-mediated inhibition of sympathetic vasoconstriction. Sprague-Dawley rats ( n = 13) were anesthetized and instrumented with an indwelling brachial artery catheter, femoral artery flow probe, and lumbar sympathetic chain stimulating electrodes. Triceps surae muscles were stimulated to contract rhythmically at 60% of maximal contractile force. In series 1 ( n = 9), the percent change in femoral vascular conductance (%FVC) in response to sympathetic stimulations delivered at 2 and 5 Hz was determined at rest and during muscle contraction before and after selective nNOS blockade with S-methyl-l-thiocitrulline (SMTC, 0.6 mg/kg iv) and subsequent nonselective NOS blockade with Nω-nitro-l-arginine methyl ester (l-NAME, 5 mg/kg iv). In series 2 ( n = 4), l-NAME was injected first, and then SMTC was injected to determine if the effect of l-NAME on constrictor responses was influenced by selective nNOS inhibition. Sympathetic stimulation decreased FVC at rest (−25 ± 7 and −44 ± 8%FVC at 2 and 5 Hz, respectively) and during contraction (−7 ± 3 and −19 ± 5%FVC at 2 and 5 Hz, respectively). The decrease in FVC in response to sympathetic stimulation was greater in the presence of SMTC at rest (−32 ± 6 and −49 ± 8%FVC at 2 and 5 Hz, respectively) and during contraction (−21 ± 4 and −28 ± 4%FVC at 2 and 5 Hz, respectively). l-NAME further increased ( P < 0.05) the sympathetic vasoconstrictor response at rest (−47 ± 4 and −60 ± 6%FVC at 2 and 5 Hz, respectively) and during muscle contraction (−33 ± 3 and −40 ± 6%FVC at 2 and 5 Hz, respectively). The effect of l-NAME was not altered by the order of nNOS inhibition. These data demonstrate that NO derived from nNOS and endothelial NOS contribute to the inhibition of sympathetic vasoconstriction in resting and contracting skeletal muscle.

scholarly journals Sex differences in sympathetic vasoconstrictor responsiveness and sympatholysis

2017 ◽  
Vol 123 (1) ◽  
pp. 128-135 ◽  
Author(s):  
Timothy P. Just ◽  
Darren S. DeLorey
Keyword(s):  
Blood Pressure ◽  
Skeletal Muscle ◽  
Sex Differences ◽  
Muscle Contraction ◽  
Vascular Resistance ◽  
Triceps Surae ◽  
Female Rats ◽  
Male Rats ◽  
Sympathetic Chain ◽  
Sympathetic Vasoconstriction

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; n = 8) and female (F; n = 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 [ Nω-nitro-l-arginine methyl ester (l-NAME), 10 mg/kg iv]. At rest, sympathetic vasoconstrictor responsiveness was augmented ( P < 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 ( P > 0.05) in females and males at 2 Hz (F: −12 ± 5%; M: −13 ± 5%) but was blunted ( P < 0.05) in females compared with males at 5 Hz (F: −24 ± 5%; M: −34 ± 8%). l-NAME increased ( P < 0.05) sympathetic vasoconstrictor responsiveness in both groups at rest and during contraction. Contraction-mediated inhibition of vasoconstriction (sympatholysis) was enhanced ( P < 0.05) in females compared with males; however, sympatholysis was not different ( P > 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. NEW & NOTEWORTHY 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.

β-Adrenoreceptors do not oppose sympathetic vasoconstriction in resting and contracting skeletal muscle of male rats

2019 ◽  
Vol 44 (11) ◽  
pp. 1230-1236
Author(s):  
Ian R. Cooper ◽  
Timothy P. Just ◽  
Darren S. DeLorey
Keyword(s):  
Skeletal Muscle ◽  
Stimulation Frequency ◽  
Triceps Surae ◽  
Male Rats ◽  
Sympathetic Chain ◽  
Sprague Dawley ◽  
Arterial Blood ◽  
Sprague Dawley Rats ◽  
Sympathetic Vasoconstriction ◽  
Response To Exercise

Sympathetic nervous system (SNS) vasoconstriction is primarily achieved through the binding of norepinephrine (NE) to α-adrenoreceptors. However, NE may also bind to β-adrenoreceptors and cause vasodilation that may oppose/blunt SNS-mediated vasoconstriction. Therefore, this study investigated the hypothesis that β-adrenoreceptor–mediated vasodilation opposes evoked vasoconstriction in resting and contracting skeletal muscle. Male (n = 9) Sprague–Dawley rats were anesthetized and surgically instrumented for stimulation of the lumbar sympathetic chain and measurement of arterial blood pressure and femoral artery blood flow. 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 skeletal muscle contraction before (control) and after β-adrenoreceptor blockade (propranolol; 0.075 mg·kg−1, intravenously). β-Adrenoreceptor blockade did not alter (P > 0.05) baseline hemodynamics or the hyperemic response to exercise. At the 2 Hz stimulation frequency, sympathetic vasoconstriction was similar (P > 0.05) in control and β-blockade conditions in resting (control, −34% ± 6%; β-blockade, −33% ± 8%) and contracting (control, −16% ± 6%; β-blockade, −14% ± 7%) muscle. At the 5 Hz stimulation frequency, sympathetic vasoconstrictor responsiveness was reduced (main effect of drug, P < 0.05) following β-blockade (rest: control, −52% ± 7%; β-blockade, −51% ± 9%; contraction: control, −32% ± 11%; β-blockade, −29% ± 13%). Novelty These data indicate that β-adrenoreceptor blockade did not augment sympathetic vasoconstriction at rest or during exercise. The study demonstrates that β-adrenoreceptors do not oppose evoked sympathetic vasoconstriction in resting or contracting skeletal muscle or contribute to functional sympatholysis.

Abstract 14842: Brain Fibroblast Growth Factor Receptor 4 Stimulation is Involved in High Phosphate Diet-Induced Skeletal Muscle Reflex Overactivation in Rats

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Han-kyul Kim ◽  
Masaki Mizuno ◽  
Gary A Iwamoto ◽  
Rie Ishizawa ◽  
Jere H Mitchell ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Cerebrospinal Fluid ◽  
Growth Factor ◽  
Muscle Contraction ◽  
Fibroblast Growth Factor ◽  
Growth Factor Receptor ◽  
Fibroblast Growth ◽  
Sprague Dawley ◽  
Muscle Reflex

An increasing number of studies have reported a deleterious role of inorganic phosphate (Pi) in promoting hypertension. Previously, we have shown high Pi diet-induced excessive pressor and sympathetic responses to muscle contraction in otherwise normal rats, which were primarily mediated by an overactive exercise pressor reflex (EPR), a reflex arising from contracting muscle. However, the mechanism underlying these abnormalities generated by excess Pi intake remains unclear. Dietary Pi is known to increase release of bone-derived fibroblast growth factor (FGF) 23 to regulate Pi homeostasis. Evidence suggests that FGF23 and FGF receptors (FGFRs) are also present in the central nervous system. The aim of this study was to determine the role of brain FGFRs in mediating augmented EPR activity induced by dietary Pi excess. Accordingly, we assessed cerebrospinal fluid FGF23 levels in Sprague-Dawley rats fed either a normal 0.6% Pi diet (NP) or a high 1.2% Pi diet (HP) for 12 weeks. To determine the role of central FGFRs in mediating the EPR, we measured mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) responses to hindlimb muscle contraction before and after intracerebroventricular (ICV) administration of either a selective FGFR4 inhibitor BLU9931 or a FGFR1/2/3 inhibitor AZD4547 in decerebrate NP and HP animals. Cerebrospinal fluid FGF23 levels were significantly higher in HP rats compared to NP rats (8.3±0.9 vs. 7.2±0.8 pM, P<0.01). ICV BLU9931 injection markedly attenuated (all P<0.01) the heightened MAP (Δ=41±14 vs. 20±14 mmHg) and RSNA (Δ=112±70 vs. 65±46 %) responses to EPR activation in HP animals, but did not significantly affect the responses in NP animals (ΔMAP=11±3 vs. 7±4 mmHg, ΔRSNA=21±17 vs. 15±5 %). MAP and RSNA responses to EPR stimulation were unchanged by ICV AZD4547 administration in NP or HP rats. In conclusion, our data demonstrate a novel action of central FGFR4 inhibition by reducing the high Pi diet-mediated skeletal muscle reflex overactivation. Importantly, the results implicate that activation of brain FGFR4 may lead to sympathetic dysregulation contributing to the abnormal hypertensive responsiveness after excess Pi consumption.

Release of nitric oxide and prostaglandin H2 to acetylcholine in skeletal muscle venules

1997 ◽  
Vol 272 (6) ◽  
pp. H2541-H2546 ◽  
Author(s):  
G. Dornyei ◽  
G. Kaley ◽  
A. Koller
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Perfusion Pressure ◽  
Thromboxane A2 ◽  
No Synthase ◽  
Gracilis Muscle ◽  
Vasoactive Agents ◽  
Before And After ◽  
Higher Doses

The role of endothelium in regulating venular resistance is not well characterized. Thus we aimed to elucidate the endothelium-derived factors involved in the mediation of responses of rat gracilis muscle venules to acetylcholine (ACh) and other vasoactive agents. Changes in diameter of perfusion pressure (7.5 mmHg)- and norepinephrine (10(-6) M)-constricted venules (approximately 225 microns in diam) to cumulative doses of ACh (10(-9) to 10(-4) M) and sodium nitroprusside (SNP, 10(-9) to 10(-4) M), before and after endothelium removal or application of various inhibitors, were measured. Lower doses of ACh elicited dilations (up to 42.1 +/- 4.7%), whereas higher doses of ACh resulted in smaller dilations or even constrictions. Endothelium removal abolished both ACh-induced dilation and constriction. In the presence of indomethacin (2.8 x 10(-5) M), a cyclooxygenase blocker, or SQ-29548 (10(-6) M), a thromboxane A2-prostaglandin H2 (PGH2) receptor antagonist, higher doses of ACh caused further dilation (up to 72.7 +/- 7%) instead of constriction. Similarly, lower doses of arachidonic acid (10(-9) to 10(-6) M) elicited dilations that were diminished at higher doses. These reduced responses were, however, reversed to substantial dilation by SQ-29548. The nitric oxide (NO) synthase blocker, N omega-nitro-L-arginine (L-NNA, 10(-4) M), significantly reduced the dilation to ACh (from 30.6 +/- 5.5 to 5.4 +/- 1.4% at 10(-6) M ACh). In contrast, L-NNA did not affect dilation to SNP. Thus ACh elicits the release of both NO and PGH2 from the venular endothelium.

scholarly journals Simvastatin Attenuates Contrast-Induced Nephropathy through Modulation of Oxidative Stress, Proinflammatory Myeloperoxidase, and Nitric Oxide

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Ketab E. Al-Otaibi ◽  
Abdulrahman M. Al Elaiwi ◽  
Mohammad Tariq ◽  
Abdulrahman K. Al-Asmari
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Femoral Vein ◽  
Lipid Hydroperoxides ◽  
Sprague Dawley ◽  
Glycerol Injection ◽  
Sprague Dawley Rats ◽  
Structural Abnormalities ◽  
Nephroprotective Effect

Contrast media- (CM-) induced nephropathy is a serious complication of radiodiagnostic procedures. Available data suggests that the development of prophylaxis strategies is limited by poor understanding of pathophysiology of CM-induced nephropathy. Present study was designed to determine the role of oxidative stress, myeloperoxidase, and nitric oxide in the pathogenesis of iohexol model of nephropathy and its modification with simvastatin (SSTN). Adult Sprague Dawley rats were divided into seven groups. After 24 h of water deprivation, all the rats except in control and SSTN-only groups were injected (10 ml/kg) with 25% glycerol. After 30 min, SSTN (15, 30, and 60 mg/kg) was administered orally, daily for 4 days. Twenty-four hours after the glycerol injection, iohexol was infused (8 ml/kg) through femoral vein over a period of 2 min. All the animals were sacrificed on day 5 and blood and kidneys were collected for biochemical and histological studies. The results showed that SSTN dose dependently attenuated CM-induced rise of creatinine, urea, and structural abnormalities suggesting its nephroprotective effect. A significant increase in oxidative stress (increased lipid hydroperoxides and reduced glutathione levels) and myeloperoxidase (MPO) and decreased nitric oxide in CM group were reversed by SSTN. These findings support the use of SSTN to combat CM-induced nephrotoxicity.

Reflex cardiovascular responses evoked by selective activation of skeletal muscle ergoreceptors

2001 ◽  
Vol 90 (1) ◽  
pp. 308-316 ◽  
Author(s):  
B. G. Leshnower ◽  
J. T. Potts ◽  
M. G. Garry ◽  
J. H. Mitchell
Keyword(s):  
Skeletal Muscle ◽  
Muscle Contraction ◽  
Cardiovascular Response ◽  
Afferent Fiber ◽  
Cardiovascular Responses ◽  
Muscle Afferents ◽  
Triceps Surae ◽  
Muscle Stretch ◽  
Group Iii ◽  
Passive Muscle

It is well known that the exercise pressor reflex (EPR) is mediated by group III and IV skeletal muscle afferent fibers, which exhibit unique discharge responses to mechanical and chemical stimuli. Based on the difference in discharge patterns of group III and IV muscle afferents, we hypothesized that activation of mechanically sensitive (MS) fibers would evoke a different pattern of cardiovascular responses compared with activation of both MS and chemosensitive (CS) fibers. Experiments were conducted in chloralose-urethane-anesthetized cats ( n = 10). Passive muscle stretch was used to activate MS afferents, and electrically evoked contraction of the triceps surae was used to activate both MS and CS muscle afferents. No significant differences were shown in reflex heart rate and mean arterial pressure (MAP) responses between passive muscle stretch and evoked muscle contraction. However, when the reflex responses were matched according to tension-time index (TTI), the peak MAP response (67 ± 4 vs. 56 ± 4 mmHg, P < 0.05) was significantly greater at higher TTI (427 ± 18 vs. 304 ± 13 kg · s, high vs. low TTI, P < 0.05), despite different modes of afferent fiber activation. When the same mode of afferent fiber activation was compared, the peak MAP response (65 ± 7 vs. 55 ± 5 mmHg, P < 0.05) was again predicted by the magnitude of TTI (422 ± 24 vs. 298 ± 19 kg · s, high vs. low TTI, P < 0.05). Total sensory input from skeletal muscle ergoreceptors, as predicted by TTI and not the modality of afferent fiber activation (muscle contraction vs. passive stretch), is suggested to be the primary determinant of the magnitude of the EPR-evoked cardiovascular response.

scholarly journals Mechanisms of sympathetic restraint in human skeletal muscle during exercise: role of α-adrenergic and nonadrenergic mechanisms

2020 ◽  
Vol 319 (1) ◽  
pp. H192-H202
Author(s):  
Alexander B. Hansen ◽  
Gilbert Moralez ◽  
Steven A. Romero ◽  
Christopher Gasho ◽  
Michael M. Tymko ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Adrenergic Receptors ◽  
Whole Body ◽  
Cycle Exercise ◽  
Vascular Conductance ◽  
Hand Grip ◽  
Vasodilatory Response ◽  
Sympathetic Vasoconstriction ◽  
Exercise Induced

Sympathetic restraint of vascular conductance to inactive skeletal muscle is critical to maintain blood pressure during moderate- to high-intensity whole body exercise. This investigation shows that cycle exercise-induced restraint of inactive skeletal muscle vascular conductance occurs primarily because of activation of α-adrenergic receptors. Furthermore, exercise-induced vasoconstriction restrains the subsequent vasodilatory response to hand-grip exercise; however, the restraint of active skeletal muscle vasodilation was in part due to nonadrenergic mechanisms. We conclude that α-adrenergic receptors are the primary but not exclusive mechanism by which sympathetic vasoconstriction restrains blood flow in humans during whole body exercise and that metabolic activity modulates the contribution of α-adrenergic receptors.

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