Aerobic muscle contraction impaired by serotonin-mediated vasoconstriction

Dora, K A; Rattigan, Stephen; Colquhoun, Eric Q.; Clark, Michael G.

doi:10.1152/jappl.1994.77.1.277

Cited by 27 publications

(34 citation statements)

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“…Serotonin constricts large arterioles (44,45) but not small arterioles (30,46), suggesting that constriction occurs at the feed arteries external to the muscle fibers. In the constant-flow perfused rat hindlimb, serotonin-mediated vasoconstriction that causes acute insulin resistance is also resistant to contractioninduced metabolic vasodilatation (47) and may preferentially affect flow within muscles rich in type II fibers (20). Insulin infusion in the present study and previously published studies (6) caused increases in 1-MX metabolism (Fig.…”

Section: Discussionmentioning

confidence: 99%

Acute vasoconstriction-induced insulin resistance in rat muscle in vivo.

1999

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Insulin-mediated changes in blood flow are associated with altered blood flow distribution and increased capillary recruitment in skeletal muscle. Studies in perfused rat hindlimb have shown that muscle metabolism can be regulated by vasoactive agents that control blood flow distribution within the hindlimb. In the present study, the effects of a vasoconstrictive agent that has no direct effect on skeletal muscle metabolism but that alters perfusion distribution in rat hindlimb was investigated in vivo to determine its effects on insulin-mediated vascular action and glucose uptake. We measured the effects of alpha-methylserotonin (alpha-met5HT) on mean arterial blood pressure, heart rate, femoral blood flow, hindlimb vascular resistance, and glucose uptake in control and euglycemic insulin-clamped (10 mU x min(-1) x kg(-1)) anesthetized rats. Blood flow distribution within the hindlimb muscles was assessed by measuring the metabolism of 1-methylxanthine (1-MX), an exogenously added substrate for capillary xanthine oxidase. Alpha-met5HT (20 microg x min(-1) x kg(-1)) infusion alone increased mean arterial blood pressure by 25% and increased hindlimb vascular resistance but caused no change in femoral blood flow. These changes were associated with decreased hindlimb 1-MX metabolism indicating less capillary flow. Insulin infusion caused decreased hindlimb vascular resistance that was associated with increased femoral blood flow and 1-MX metabolism. Treatment with alpha-met5HT infusion commenced before insulin infusion prevented the increase in femoral blood flow and inhibited the stimulation of 1-MX metabolism. Alpha-met5HT infusion had no effect on hindlimb glucose uptake but markedly inhibited the insulin stimulation of glucose uptake (P < 0.05) and was associated with decreased glucose infusion rates to maintain euglycemia (P < 0.05). A significant correlation (P < 0.05) was observed between 1-MX metabolism and hindlimb glucose uptake but not between femoral blood flow and glucose uptake. The results indicate that in vivo, certain types of vasoconstriction in muscle such as elicited by 5HT2 agonists, which prevent normal insulin recruitment of capillary flow, cause impaired muscle glucose uptake. Moreover, if vasoconstriction of this kind results from stress-induced increase in sympathetic outflow, then this may provide a clue as to the link between hypertension and insulin resistance that is often observed in humans.

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Section: Discussionmentioning

confidence: 99%

Acute vasoconstriction-induced insulin resistance in rat muscle in vivo.

1999

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“…In contrast, Type B vasoconstrictors (e.g. 5‐HT) markedly inhibit V˙ O 2 , lactate and glycerol efflux, other metabolic changes and depress tetanic tension development ( Dora et al . 1994 , Clark et al .…”

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confidence: 99%

Microsphere infusion reverses vasoconstrictor‐mediated change in hindlimb oxygen uptake and energy status

Vincent

Rattigan

Clark

1998

Acta Physiologica Scandinavica

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The vasoconstrictors, angiotensin II (AII) and serotonin (5-HT) produce opposing metabolic effects and appear to control different flow routes in the constant-flow perfused rat hindlimb. In the present study the association between vascular flow route recruitment and metabolism was assessed by selective microsphere embolism of either route. Microspheres (MS, 11.9 +/- 0.1 microns, mean +/- SE diameter) were injected during AII, 5-HT or vehicle infusions (basal conditions) and the effects on hindlimb (4.7 +/- 0.1 g muscle) oxygen uptake (VO2) and indices of energy status CrP/Cr, CrP/ATP and energy charge (EC) of the calf muscle group assessed. MS (1.5 x 10(6)) injected during vehicle, or 5-HT infusion increased VO2 (P < 0.05) but did not affect energy status. During AII, MS decreased VO2. Change in VO2 correlated positively with CrP/Cr (r = 0.68, P < 0.0001) and CrP/ATP (r = 0.51, P < 0.001) but not EC (r = 0.08, P = 0.59). MS (1.5 x 10(6)) increased pressure but did not affect the flow rate. The metabolic changes resulting from 1.5 x 10(6) microspheres were intensified by a second injection of 1.5 x 10(6) microspheres but further injection (> 3.0 x 10(6) microspheres) began to inhibit flow. It is concluded that a finite number (< or = 3.0 x 10(6)) of microspheres of 11.9 microns diameter has opposite effects on VO2 depending on the vasoconstrictor present and that these effects result from the occlusion of the different vascular route accessed by each vasoconstrictor. The data support the proposal that hindlimb metabolism can be controlled by vasoconstrictors as a result of selective vascular recruitment.

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“…An explanation for the resistance of high‐dose ET‐1‐mediated vasoconstriction to contraction may relate to the site of action where the vasoconstriction is taking place. In a previous study, 5‐HT was shown to be resistant to vasodilation caused by electrical stimulation 10 and this agonist is known to have receptors on larger vessels, such as the feed arteries, which are external to muscle and either insensitive or inaccessible to the metabolic vasodilation from muscle contraction. Accordingly, the resistance of high‐dose ET‐1‐mediated vasoconstriction to contraction may be similarly explained.…”

Section: Discussionmentioning

confidence: 99%

“…Following the 30 min equilibration period at 8 mL/min, the flow rate was adjusted as indicated in the protocols to 15 mL/min (1 mL/min per g wet weight muscle) and the resting length of the muscle was adjusted to obtain maximal active tension on stimulation. A Nerv‐Muskel‐Reizgerat stimulator (Hugo Sachs Elektroniks, March‐Hugstetten, Germany) administered 0.1 msec pulse at 0.5 Hz with appropriate voltage for maximal stimulation (full fibre recruitment) 10,16 …”

Section: Methodsmentioning

confidence: 99%

“…Changes in microcirculatory flow caused by various vasoconstrictors can lead to impaired delivery of insulin and glucose to skeletal muscle, causing insulin resistance, 9,10 and may also limit exercise capacity due to reduced oxygen availability. A previous study from this laboratory has shown that ET‐1 has dose‐dependent stimulatory and inhibitory effects on metabolism that arise from its effects to redistribute flow by vasoconstriction 11 .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Potential for Endothelin‐1‐mediated Impairment of Contractile Activity in Hypertension

Kolka

Rattigan

Richards

et al. 2007

Clin Exp Pharma Physio

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1. The present study examined the potential for reduced exercise capacity observed in hypertensive patients as a result of elevated levels of endothelin (ET)-1. We have previously reported that ET-1 exerts low-dose stimulatory or high-dose inhibitory effects on the metabolism of the rat isolated perfused hindlimb from its vasoconstrictor activity. 2. Herein, we determined whether there are similar effects on tension development by the rat isolated constant-flow hindlimb during ET-1-mediated vasoconstriction. 3. The dose-dependent vasoconstrictor effects of ET-1 on metabolism in contracting muscle were the same as those observed previously in resting muscle. Highest concentrations of ET-1 gave rise to a transient stimulation followed by a marked inhibition of tension development, consistent with a decrease in aerobic capacity of the muscle. The vasoconstriction due to the higher doses of ET-1 was not dilated by electrical stimulation. 4. In conclusion, the biphasic nature of the actions of ET-1 suggests that although lower concentrations of ET-1 do not affect exercise capacity, higher concentrations that may occur in hypertension are inhibitory to metabolism and aerobic capacity of muscle. The inhibitory effects of ET-1 appear to result from enhanced functional shunting.

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Aerobic muscle contraction impaired by serotonin-mediated vasoconstriction

Cited by 27 publications

References 0 publications

Acute vasoconstriction-induced insulin resistance in rat muscle in vivo.

Acute vasoconstriction-induced insulin resistance in rat muscle in vivo.

Microsphere infusion reverses vasoconstrictor‐mediated change in hindlimb oxygen uptake and energy status

Potential for Endothelin‐1‐mediated Impairment of Contractile Activity in Hypertension

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