Vasopressin and angiotensin II stimulate oxygen uptake in the perfused rat hindlimb

Colquhoun, Eric Q.; Hettiarachchi, Manthinda; Ye, Ji-Ming; Richter, Erik A.; Hniat, Andrew J.; Rattigan, Stephen; Clark, Michael G.

doi:10.1016/0024-3205(88)90487-0

Cited by 61 publications

(42 citation statements)

References 17 publications

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“…Perfused rat hindlimb studies: surgery Hindlimb surgery was performed as described by others [16] with additional details by us as outlined elsewhere [17]. In brief, the rats were anaesthetised with Nembutal (5-6 mg/100-g body weight, i.p.)…”

Section: Experiments In Vivo: Expression Of Resultsmentioning

confidence: 99%

Vascular and metabolic effects of methacholine in relation to insulin action in muscle

et al. 2006

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Aims/hypothesis: Methacholine (MC) is a nitric oxide vasodilator, but unlike other vasodilators, it potentiates insulin-mediated glucose uptake by muscle. The present study aimed to resolve whether this action was the result of a vascular effect of MC leading to increased muscle perfusion or a direct effect of MC on the myocytes. We hypothesise that vascular-mediated insulin-stimulated glucose uptake responses to MC occur at lower doses than direct myocyte MC-mediated increases in glucose uptake. Methods: The vascular and metabolic effects of this vasodilator were examined in rats in vivo using a novel local infusion technique, and in the pump-perfused rat hindlimb under conditions of constant flow. Results: Local infusion of low-dose MC (0.3 μmol/l) into the epigastric artery of one leg (test) in vivo markedly increased femoral blood flow and decreased vascular resistance, without effects in the contra-lateral leg. Capillary recruitment, but not glucose uptake, was increased in the test leg. All increases caused by MC were confined to the test leg and blocked by local infusion into the test leg of N ω -nitro-L-arginine methyl ester (L-NAME), but not by infusion of N ω -nitro-D-arginine methyl ester (D-NAME). In the constant-flow pumpperfused rat hindlimb, infusion of 0.6 μmol/l MC vasodilated the pre-constriction effected by 70 nmol/l noradrenaline or 300 nmol/l serotonin, and this was blocked by 10 μmol/l L-NAME. 2-Deoxyglucose in muscle was increased by 30 μmol/l MC (p<0.05), but was unaffected by 3 μmol/l MC. All increases in 2-deoxyglucose uptake by 30 μmol/l MC were blocked by 10 μmol/l L-NAME. Conclusions/interpretation: MC has dose-dependent effects both on the vasculature and on muscle metabolism. At low dose (0.3-3 μmol/l), MC is a potent vasodilator in muscle, both in vivo and in vitro, without metabolic effects; at higher doses (≥30 μmol/l) MC has a direct metabolic effect leading to increased glucose uptake. Both the vascular and metabolic effects are sensitive to L-NAME. The lowdose enhancement of insulin action in vivo by MC, which has been reported previously, thus seems to be attributable to vascular effects.

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Section: Experiments In Vivo: Expression Of Resultsmentioning

confidence: 99%

Vascular and metabolic effects of methacholine in relation to insulin action in muscle

et al. 2006

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“…Isolated hind limb autoperfusion and perfusion pressure recording were performed as described previously (Colquhoun et al, 1988). In brief, after administration of heparin sodium (1000 U/kg, i.v.…”

Section: Methodsmentioning

confidence: 99%

Tissue-Specific Regulation of Microvascular Diameter: Opposite Functional Roles of Neuronal and Smooth Muscle Located Vanilloid Receptor-1

et al. 2008

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The transient receptor potential type V1 channel (vanilloid receptor 1, TRPV1) is a Ca 2ϩ -permeable nonspecific cation channel activated by various painful stimuli including ischemia. We hypothesized that TRPV1 is expressed in the arterioles and is involved in the regulation of microvascular tone. We found that TRPV1 stimulation by capsaicin (intra-arterial administration) of the isolated, perfused right hind limb of the rat increased vascular resistance (by 98 Ϯ 21 mm Hg at 10 g) in association with decreased skeletal muscle perfusion and elevation of skin perfusion (detected by dual-channel laser Doppler flowmetry). Denervation of the hind limb did not affect capsaicin-evoked changes in vascular resistance and tissue perfusion in the hind limb but reduced the elevation of perfusion in the skin. In isolated, pressurized skeletal (musculus gracilis) muscle arterioles (diameter, 147 Ϯ 35 m), capsaicin had biphasic effects: at lower concentrations, capsaicin (up to 10 nM) evoked dilations (maximum, 32 Ϯ 13%), whereas higher concentrations (0.1-1 M) elicited substantial constrictions (maximum, 66 Ϯ 7%). Endothelium removal or inhibition of nitric-oxide synthase abolished capsaicin-induced dilations but did not affect arteriolar constriction. Expression of TRPV1 was detected by reverse transcriptase-polymerase chain reaction in the aorta and in cultured rat aortic vascular smooth muscle cells (A7r5). Immunohistochemistry revealed expression primarily in the smooth muscle layers of the gracilis arteriole. These data demonstrate the functional expression of TRPV1 in vascular smooth muscle cells mediating vasoconstriction of the resistance arteries. Because of the dual effects of TRPV1 stimulation on the arteriolar diameter (dilation in skin, constriction in skeletal muscle), we propose that TRPV1 ligands represent drug candidates for tissue-specific modulation of blood distribution.The transient receptor potential type V1 channel (vanilloid receptor-1, TRPV1) is a nonselective cation channel, structurally belonging to the transient receptor potential family of ion channels. TRPV1 is found in sensory C and A-␦ fibers (Caterina et al., 1997) and functions as a ligand-, proton-, and heat-activated molecular integrator of nociceptive stimuli in the periphery (Szallasi and Blumberg, 1999;

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“…Surgery was performed to isolate one hindlimb as previously described [33,34]. Immediately following surgery the animals were killed with an intracardiac injection of pentobarbital sodium and a single hindlimb perfusion was carried out as previously described [23].…”

Section: Study 2: Isolated Constant-flow Hindlimb Perfusionmentioning

confidence: 99%

A vascular mechanism for high-sodium-induced insulin resistance in rats

et al. 2014

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Aims/hypothesis High sodium (HS) effects on hypertension are well established. Recent evidence implicates a relationship between HS intake and insulin resistance, even in the absence of hypertension. The aim of the current study was to determine whether loss of the vascular actions of insulin may be the driving factor linking HS intake to insulin resistance. Methods Sprague Dawley rats were fed a control (0.31% wt/wt NaCl) or HS (8.00% wt/wt NaCl) diet for 4 weeks and subjected to euglycaemic-hyperinsulinaemic clamp (10 mU min) or constant-flow pump-perfused hindlimb studies following an overnight fast. A separate group of HS rats was given quinapril during the dietary intervention and subjected to euglycaemichyperinsulinaemic clamp as above. Results HS intake had no effect on body weight or fat mass or on fasting glucose, insulin, endothelin-1 or NEFA concentrations. However, HS impaired whole body and skeletal muscle glucose uptake, in addition to a loss of insulin-stimulated microvascular recruitment. These effects were present despite enhanced insulin signalling (Akt) in both liver and skeletal muscle. Constant-flow pump-perfused hindlimb experiments revealed normal insulin-stimulated myocyte glucose uptake in HS-fed rats. Quinapril treatment restored insulin-mediated microvascular recruitment and muscle glucose uptake in vivo.Conclusions/interpretation HS-induced insulin resistance is driven by impaired microvascular responsiveness to insulin, and is not due to metabolic or signalling defects within myocytes or liver. These results imply that reducing sodium intake may be important not only for management of hypertension but also for insulin resistance, and highlight the vasculature as a potential therapeutic target in the prevention of insulin resistance.

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Vasopressin and angiotensin II stimulate oxygen uptake in the perfused rat hindlimb

Cited by 61 publications

References 17 publications

Vascular and metabolic effects of methacholine in relation to insulin action in muscle

Vascular and metabolic effects of methacholine in relation to insulin action in muscle

Tissue-Specific Regulation of Microvascular Diameter: Opposite Functional Roles of Neuronal and Smooth Muscle Located Vanilloid Receptor-1

A vascular mechanism for high-sodium-induced insulin resistance in rats

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