Dilation of isolated skeletal muscle arterioles by insulin is endothelium dependent and nitric oxide mediated

1996 ◽  
Vol 270 (6) ◽  
pp. H2120-H2124 ◽  
Author(s):  
Y. L. Chen ◽  
E. J. Messina
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Cardiac Output ◽  
Flow State ◽  
Insulin Administration ◽  
Cremaster Muscle ◽  
Response Curves ◽  
Solution Ph ◽  
First Order ◽  
Before And After

Studies in humans and animals have shown that insulin administration increases cardiac output and both forearm and hindlimb blood flow. In this study we tested the hypothesis that insulin dilates skeletal muscle arterioles and that the dilation is endothelium dependent. First-order arterioles (77 microns) from rat cremaster muscle were isolated, pressurized (65 mmHg), equilibrated in a Krebs bicarbonate-buffered solution (pH 7.4) gassed with 10% O2 (5% CO2-85% N2), and studied in a no-flow state. Cumulative concentration-response curves to insulin (10 microU/ml-10 mU/ml) were obtained in intact arterioles before and after either endothelium removal or administration of indomethacin (Indo, 10(-5) M) or nitro-L-arginine (L-NNA, 10(-4) M). Insulin evoked concentration-dependent increases in control diameter of 13-61%, which were completely inhibited by endothelium removal or L-NNA. In contrast, Indo had no effect on insulin-evoked arteriolar dilation. These results indicate that dilation to insulin in skeletal muscle arterioles is endothelium dependent and mediated by nitric oxide.

Inhibition of NO synthesis or endothelium removal reveals a vasoconstrictor effect of insulin on isolated arterioles

1999 ◽  
Vol 276 (3) ◽  
pp. H815-H820 ◽  
Author(s):  
C. Andrew Schroeder ◽  
Ya-Li Chen ◽  
Edward J. Messina
Keyword(s):  
Vascular Tone ◽  
Peripheral Resistance ◽  
Flow State ◽  
State Control ◽  
Response Curves ◽  
Solution Ph ◽  
First Order ◽  
Before And After ◽  
Gastrocnemius Muscles ◽  
Regulation Of Vascular Tone

In this study we tested the hypothesis that insulin may differentially affect isolated arterioles from red (RGM) and white gastrocnemius muscles (WGM) because of their differences in function and metabolic profile. We also determined whether the responses of these arterioles are endothelium dependent and mediated by either prostaglandins or nitric oxide (NO). Arterioles were isolated, pressurized to 85 mmHg, equilibrated in Krebs bicarbonate-buffered solution (pH 7.4) gassed with 10% O2 (5% CO2-85% N2), and studied in a no-flow state. Control diameters for first-order arterioles from RGM averaged 77 ± 8 μm and from WGM averaged 77 ± 5 μm. Cumulative dose-response curves to insulin (10 μU/ml, 100 μU/ml, 1 mU/ml, and 10 mU/ml) were obtained in arterioles before and after endothelium removal or administration of either indomethacin (Indo, 10−5 M) or N G-nitro-l-arginine (l-NNA, 10−4 M). Insulin evoked concentration-dependent increases in control diameter of intact RGM and WGM arterioles of 6–26% and 9–28%, respectively. Indo was without any effect on insulin-induced dilation in RGM and WGM arterioles. Insulin-evoked dilation in both RGM and WGM arterioles was completely inhibited and converted to vasoconstriction by endothelium removal and administration of l-NNA. These results indicate that in endothelium-intact arterioles from RGM and WGM, insulin evokes an endothelium-dependent dilation that is equivalent and mediated by NO. In contrast, in the absence of a functional endothelium, insulin evokes arteriolar constriction. The finding that insulin can constrict arterioles, at physiological concentrations, suggests that insulin may play a more significant role in the regulation of vascular tone and total peripheral resistance than previously appreciated.

C-peptide induces a concentration-dependent dilation of skeletal muscle arterioles only in presence of insulin

1999 ◽  
Vol 276 (4) ◽  
pp. H1223-H1228 ◽  
Author(s):  
Michael E. Jensen ◽  
Edward J. Messina
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Flow State ◽  
Solution Ph ◽  
C Peptide ◽  
First Order ◽  
Arteriolar Diameter ◽  
Significant Concentration

In this study we tested the hypothesis that C-peptide alone or in conjunction with insulin may cause a dilation of skeletal muscle arterioles. First-order arterioles (88 μm) isolated from rat cremaster muscles were pressurized (65 mmHg), equilibrated in a Krebs bicarbonate-buffered solution (pH 7.4), gassed with 10% O2 (balance 5% CO2, 85% N2), and studied in a no-flow state. C-peptide administered at concentrations of 0.3, 1, 3, 10, 100, 300, and 1,000 ng/ml evoked arteriolar dilation that was not concentration dependent. In contrast, the administration of the four lower physiological concentrations of C-peptide to arterioles exposed to a nondilating concentration of insulin evoked a significant concentration-dependent increase in arteriolar diameter from 8.6 to 42.3% above control. The arteriolar dilation to C-peptide in the presence of insulin was completely inhibited by administration of N G-nitro-l-arginine (10−4 M). Responses to ACh and adenosine were not enhanced when these drugs were administered in the presence of insulin. These results indicate that C-peptide has the capacity to evoke arteriolar dilation in skeletal muscle via a nitric oxide-mediated mechanism that appears to be enhanced by an interaction with insulin. Furthermore, the effects of insulin appear to be specific for C-peptide and are not the result of a general enhancement of endothelium-dependent or endothelium-independent dilation.

Endothelium-dependent dilation to L-arginine in isolated rat skeletal muscle arterioles

1992 ◽  
Vol 262 (4) ◽  
pp. H1211-H1216 ◽  
Author(s):  
D. Sun ◽  
E. J. Messina ◽  
A. Koller ◽  
M. S. Wolin ◽  
G. Kaley
Keyword(s):  
Skeletal Muscle ◽  
Solution Ph ◽  
Microvascular Endothelium ◽  
Local Regulation ◽  
First Order ◽  
Relaxing Factor ◽  
Before And After ◽  
Arteriolar Resistance ◽  
Endothelium Derived Relaxing Factor ◽  
Dose Dependent

The vascular actions of L-arginine (L-Arg) were studied in isolated, pressurized first-order rat cremaster muscle arterioles (93 +/- 2.9 microns) bathed in a Krebs bicarbonate-buffered solution, pH 7.4, equilibrated with 21% O2-5% CO2. Arterioles were studied before and after either the administration of NG-nitro-L-arginine (L-NNA, 10(-3) M), an inhibitor of the synthesis of endothelium-derived relaxing factor (EDRF), or the removal of the endothelium. Acetylcholine (ACh, 10(-8) and 10(-6) M), sodium nitroprusside (SNP, 10(-8) M) and phenylephrine (PE, 10(-7) M) evoked dilation and constriction, respectively. L-Arg, (10(-5)-10(-3) M) the precursor of EDRF, evoked dose-dependent arteriolar dilation; whereas D-arginine (D-Arg, 10(-5)-10(-3) M) was without any significant effect. Administration of L-NNA significantly reduced basal diameters and significantly inhibited the arteriolar dilations to both ACh and L-Arg but had no effect on the dilation to SNP. Removal of the arteriolar endothelium with air inhibited dilations to both ACh and L-Arg, had no effect on responses to SNP, and potentiated vasoconstrictor responses to PE. These findings suggest that in skeletal muscle arterioles the dilations to ACh and L-Arg are endothelium dependent and that microvascular endothelium modulates constrictor responses to PE. Thus EDRF may play an important role in the local regulation of arteriolar resistance and blood flow.

Systemic and regional hemodynamics after nitric oxide synthase inhibition: role of a neurogenic mechanism

1994 ◽  
Vol 267 (1) ◽  
pp. R84-R88 ◽  
Author(s):  
M. Huang ◽  
M. L. Leblanc ◽  
R. L. Hester
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Cardiac Output ◽  
No Synthase ◽  
Before And After ◽  
Regional Hemodynamics ◽  
Autonomic Blockade ◽  
Infusion Of Norepinephrine ◽  
Oxide Synthase

The study tested the hypothesis that the increase in blood pressure and decrease in cardiac output after nitric oxide (NO) synthase inhibition with N omega-nitro-L-arginine methyl ester (L-NAME) was partially mediated by a neurogenic mechanism. Rats were anesthetized with Inactin (thiobutabarbital), and a control blood pressure was measured for 30 min. Cardiac output and tissue flows were measured with radioactive microspheres. All measurements of pressure and flows were made before and after NO synthase inhibition (20 mg/kg L-NAME) in a group of control animals and in a second group of animals in which the autonomic nervous system was blocked by 20 mg/kg hexamethonium. In this group of animals, an intravenous infusion of norepinephrine (20-140 ng/min) was used to maintain normal blood pressure. L-NAME treatment resulted in a significant increase in mean arterial pressure in both groups. L-NAME treatment decreased cardiac output approximately 50% in both the intact and autonomic blocked animals (P < 0.05). Autonomic blockade alone had no effect on tissue flows. L-NAME treatment caused a significant decrease in renal, hepatic artery, stomach, intestinal, and testicular blood flow in both groups. These results demonstrate that the increase in blood pressure and decreases in cardiac output and tissue flows after L-NAME treatment are not dependent on a neurogenic mechanism.

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.

Microvascular response to blockade of prostaglandin synthesis in rat skeletal muscle

1982 ◽  
Vol 243 (1) ◽  
pp. H51-H60 ◽  
Author(s):  
J. E. Faber ◽  
P. D. Harris ◽  
I. G. Joshua
Keyword(s):  
Skeletal Muscle ◽  
Cremaster Muscle ◽  
Local Blood Flow ◽  
Local Inhibition ◽  
Microvascular Response ◽  
Before And After ◽  
Endogenous Prostaglandins ◽  
The Moment ◽  
Arteriolar Tone ◽  
Arteriolar Diameter

The contribution of endogenous prostaglandins (PGs) to the control of arteriolar diameter in the microcirculation is incompletely defied and has only been studied in drug-anesthetized animals. To test the possibility that endogenous PGs are tonically released to exert a net dilator influence at certain levels in the microcirculation, television microscopy was used to quantitate the arteriolar responses in the rat cremaster muscle to local blockade of PG synthesis with indomethacin. Rats were decerebrated by a midcollicular transection and were allowed to recover from surgical anesthesia. The cremaster muscle with intact circulation and innervation was suspended by sutures in a temperature-controlled Krebs bath. Diameters, vasomotion frequency, and vasomotion amplitude of arterioles at several anatomic levels were measured before and after local inhibition of PG synthesis in the presence and absence of alpha-adrenergic receptor blockade. Inhibition of PG synthesis produced marked constriction (42-66% of control) at all arteriolar levels, with greater responses occurring in the smaller arterioles. PG synthesis blockade increased vasomotion frequency in arterioles that exhibited spontaneous vasomotion during control periods, and blockade induced vasomotion in vessels lacking spontaneous vasomotion. Pretreatment with phentolamine significantly attenuated the constriction and augmentation of vasomotion. These data indicate that dilator PGs participate in the moment-to-moment regulation of arteriolar tone and local blood flow in skeletal muscle. Further, their mechanism of action may involve alterations in neuronal norepinephrine release or alpha-receptor sensitivity.

Regional blood flows and cardiac output distribution in rats during acute anemia or polycythemia

1980 ◽  
Vol 58 (4) ◽  
pp. 411-415 ◽  
Author(s):  
U. Ackermann ◽  
A. T. Veress
Keyword(s):  
Skeletal Muscle ◽  
Cardiac Output ◽  
Metabolic Factors ◽  
Nervous Control ◽  
Blood Flows ◽  
Before And After ◽  
Regional Blood Flows ◽  
Normovolemic Anemia ◽  
Flow Changes ◽  
Vascular Beds

Radioactively labelled microspheres (15 μm diameter) were used to measure cardiac output (CO) distribution and blood flows in spleen, kidneys, and skeletal muscle before and after normovolemic anemia or polycythemia in anesthetized rats. Hematocrits were changed from 45 to 33% or from 45 to 59% by an exchange transfusion of homologous plasma or packed cells. Anemia was accompanied by a 39% increase in CO while polycythemia showed a 25% decrease. Following hemodilution the spleen as well as skeletal muscle received greater than normal fractions of CO and in each the flow increase was greater than expected from the fall in viscosity. The renal fraction of CO was unchanged. Following hemoconcentration "greater-than-normal" fractions of CO were distributed towards spleen and kidney. In these tissues the changes in flow were significantly greater than the change in resistance due to viscosity. Skeletal muscle flow changes appeared to have been due mostly to increased viscosity. These observations imply that during acute, isovolemic changes in hematocrit, the flow changes of individual vascular beds cannot be explained by viscosity changes alone but the importance of nervous control or of local metabolic factors remains to be investigated.

Adrenergic facilitation of myogenic response in skeletal muscle arterioles

1991 ◽  
Vol 260 (5) ◽  
pp. H1424-H1432 ◽  
Author(s):  
G. A. Meininger ◽  
J. E. Faber
Keyword(s):  
Skeletal Muscle ◽  
The Body ◽  
Myogenic Response ◽  
Receptor Blockade ◽  
Cremaster Muscle ◽  
First Order ◽  
Beta Receptor Blockade ◽  
Denervated Muscles ◽  
Dose Dependent ◽  
Intravascular Pressure

The myogenic response was studied in large skeletal muscle arterioles in the presence of varying degrees of constriction with norepinephrine (NE; 3 x 10(-8) to 1 x 10(-5) M) or potassium chloride (KCl, 40-120 mM). The cremaster muscle of anesthetized rats was exteriorized into a Krebs-filled tissue bath chamber for observation of the microvasculature using a video microscopy system. The body of the rats was enclosed in an airtight Plexiglas box that was pressurized from 0 to +30 mmHg to raise intravascular pressure and elicit the myogenic response. All experiments were performed in acutely denervated muscles with propranolol (1 x 10(-6) M) present to produce beta-receptor blockade. Diameter responses of the first-order arteriole (1A) were measured with a videoimage caliper and intravascular pressure with the servo-null micropipette technique. Under basal conditions, without NE, 1A diameter increased in a passivelike fashion from 122 +/- 5.4 to 130 +/- 5.1 microns as box pressure was elevated from 0 to +30 mmHg, respectively. Addition of NE to the cremaster bath produced a dose-dependent constriction of the 1A (EC50 2 x 10(-7) M). In the presence of this adrenergic tone the 1A exhibited myogenic constriction in response to increases in box pressure. For example, topical application of 3 X 10(-7) M NE caused the 1A to constrict from 122 +/- 5.4 to 70 +/- 5.3 microns. In the presence of this adrenergic tone elevating box pressure from 0 to +30 mmHg caused additional constriction to 55 +/- 6.6 microns.(ABSTRACT TRUNCATED AT 250 WORDS)

Heart failure alters the strength and mechanisms of arterial baroreflex pressor responses during dynamic exercise

2004 ◽  
Vol 287 (4) ◽  
pp. H1682-H1688 ◽  
Author(s):  
Jong-Kyung Kim ◽  
Robert A. Augustyniak ◽  
Javier A. Sala-Mercado ◽  
Robert L. Hammond ◽  
Eric J. Ansorge ◽  
...  
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Cardiac Output ◽  
Pressor Response ◽  
Normal Subjects ◽  
Dynamic Exercise ◽  
Arterial Baroreflex ◽  
Bilateral Carotid Occlusion ◽  
Bilateral Carotid ◽  
Before And After

Arterial baroreflex function is well preserved during dynamic exercise in normal subjects. In subjects with heart failure (HF), arterial baroreflex ability to regulate blood pressure is impaired at rest. However, whether exercise modifies the strength and mechanisms of baroreflex responses in HF is unknown. Therefore, we investigated the relative roles of cardiac output and peripheral vasoconstriction in eliciting the pressor response to bilateral carotid occlusion (BCO) in conscious, chronically instrumented dogs at rest and during treadmill exercise ranging from mild to heavy workloads. Experiments were performed in the same animals before and after rapid ventricular pacing-induced HF. At rest, the pressor response to BCO was significantly attenuated in HF (33.3 ± 1.2 vs. 18.7 ± 2.7 mmHg), and this difference persisted during exercise in part due to lower cardiac output responses in HF. However, both before and after the induction of HF, the contribution of vasoconstriction in active skeletal muscle toward the pressor response became progressively greater as workload increased. We conclude that, although there is an impaired ability of the baroreflex to regulate arterial pressure at rest and during exercise in HF, vasoconstriction in active skeletal muscle becomes progressively more important in mediating the baroreflex pressor response as workload increases with a pattern similar to that observed in normal subjects.

scholarly journals Acute hyperglycemia depresses arteriolar NO formation in skeletal muscle

1999 ◽  
Vol 277 (4) ◽  
pp. H1513-H1520 ◽  
Author(s):  
J. M. Lash ◽  
G. P. Nase ◽  
H. G. Bohlen
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
No Production ◽  
Acute Hyperglycemia ◽  
Vascular Responses ◽  
No Formation ◽  
Oxide Concentration ◽  
Before And After ◽  
Arteriolar Wall ◽  
Nitric Oxide Concentration

In the rat intestinal and cerebral microvasculatures, acute d-glucose hyperglycemia suppresses endothelium-dependent dilation to ACh without affecting endothelium-independent dilation to nitroprusside. This study determined whether acute hyperglycemia suppressed arteriolar wall nitric oxide concentration ([NO]) at rest or during ACh stimulation and inhibited nitroprusside-, ACh- or contraction-induced dilation of rat spinotrapezius arterioles. Vascular responses were measured before and after 1 h of topical 300 mg/100 mld-glucose; arteriolar [NO] was measured with NO-sensitive microelectrodes. Arteriolar dilation to ACh was not significantly altered after superfusion of 300 mg/100 mld-glucose. However, after hyperglycemia, arteriolar [NO] was not increased by ACh, compared with a 300 nM increase attained during normoglycemia. Arteriolar dilation to submaximal nitroprusside and muscle contractions was enhanced by hyperglycemia. These results indicated that in the rat spinotrapezius muscle, acute hyperglycemia suppressed arteriolar NO production while simultaneously augmenting vascular smooth muscle responsiveness to nitroprusside, presumably through cGMP-mediated mechanisms. In effect, this may have allowed ACh- and muscle contraction-induced vasodilation to be maintained during hyperglycemia despite an impaired NO system.

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