scholarly journals Insulin Resistance and Hypertension*In Vivo and In Vitro Insulin Action in Skeletal Muscle in Spontaneously Hypertensive and Wistar Kyoto Rats

1997 ◽  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Insulin Action ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto Rats ◽  
Wistar Kyoto

Proton efflux from rat skeletal muscle in vivo: changes in hypertension

1992 ◽  
Vol 82 (5) ◽  
pp. 489-491 ◽  
Author(s):  
G. J. Kemp ◽  
C. H. Thompson ◽  
G. K. Radda
Keyword(s):  
Skeletal Muscle ◽  
Intracellular Ph ◽  
Spontaneously Hypertensive Rats ◽  
Hypertensive Rats ◽  
Proton Efflux ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto Rats ◽  
Wistar Kyoto

1. An analysis of the recovery kinetics of intracellular pH and phosphocreatine concentration after exercise in skeletal muscle was developed to calculate the rate of proton efflux in vivo. 2. Recovery of rat leg muscle pH after sciatic nerve stimulation was faster in spontaneously hypertensive rats than in Wistar-Kyoto controls (both n = 5). 3. Analysis of these data showed that the rate of proton efflux depends on intracellular pH, being greater at lower pH. 4. The early rate of proton efflux was greater in spontaneously hypertensive rats [measured over the first 0.8 min, 12.5 mmol min−1 kg−1 (sem 1.8) in spontaneously hypertensive rats compared with 7.6 mmol min−1 kg−1 (sem 0.4) in Wistar-Kyoto rats, P < 0.05], even though pH at the start of recovery was higher [6.30 (sem 0.03) in spontaneously hypertensive rats compared with 6.17 (sem 0.01) in Wistar-Kyoto rats, P < 0.01]. 5. This novel analysis provides a quantitative estimate of the rate of proton efflux in vivo, and demonstrates directly that this is increased in spontaneously hypertensive rats, as has previously been inferred from pH changes during exercise and studies of cultured muscle cells in vitro.

Na+/H+ and HCO3−/Cl− exchange in the control of intracellular pH in vivo in the spontaneously hypertensive rat

1991 ◽  
Vol 81 (6) ◽  
pp. 743-750 ◽  
Author(s):  
P. D. Syme ◽  
J. K. Aronson ◽  
C. H. Thompson ◽  
E. M. Williams ◽  
Y. Green ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Intracellular Ph ◽  
Acid Concentration ◽  
Spontaneously Hypertensive Rats ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto Rats ◽  
Concentration Changes ◽  
Wistar Kyoto

1. We have previously shown that the cytosolic acid concentration changes in skeletal muscle during contraction in spontaneously hypertensive rats and normotensive Wistar-Kyoto rats in vivo. We have now found that this change was unaffected by 20% inhaled CO2 or by 4,4′-di-isothiocyanostilbene-2,2′-disulphonate. This is evidence that HCO3− exchange in vivo is not important in the control of cytosolic acid concentration during skeletal muscle contraction in either spontaneously hypertensive or Wistar-Kyoto rats. 2. We have also previously shown that the difference in cytosolic acid response during contraction between spontaneously hypertensive and Wistar-Kyoto rats is due to increased Na+/H+ antiporter activity in the spontaneously hypertensive rats. Our current findings suggest that this increase in Na+/H+ antiporter activity is more likely to be due to a change in the Km of the antiporter than to a change in the Vmax. We estimate that the Km of the antiporter changes in hypertension from pH 7.16 to 7.33. 3. We did not find any differences between adult spontaneously hypertensive and Wistar-Kyoto rats with regard to resting intracellular and extracellular pH and resting intracellular and extracellular HCO3− concentrations. In addition, we did not find any evidence of a difference in skeletal muscle HCO3−/Cl− exchange between adult spontaneously hypertensive and Wistar-Kyoto rats. 4. At rest, skeletal muscles of the spontaneously hypertensive and Wistar-Kyoto rats have the same lactate production, HCO3−/Cl− exchange and arterial partial pressure of CO2. In addition, we can also calculate that at a resting intracellular pH of 7.05 in the spontaneously hypertensive rats, the antiporter is 66% saturated. The corresponding value in the Wistar-Kyoto rats (resting intracellular pH 7.04) is 57%. This explains the lack of difference in resting intracellular pH between the two strains of rat and suggests that at rest differences in Na+/H+ antiporter activity due to a shift in Km of the antiporter are too small to result in a difference in resting pH. 5. Furthermore, Na+/H+ antiporter activity around pH 7.0 was unable to prevent the acidosis caused by CO2 loading. Thus resting pH in skeletal muscle in vivo is determined largely by the HCO3− system and in this regard skeletal muscle is similar to vascular smooth muscle.

scholarly journals Effect of inhibition of glutathione synthesis on insulin action: in vivo and in vitro studies using buthionine sulfoximine

2000 ◽  
Vol 349 (2) ◽  
pp. 579-586 ◽  
Author(s):  
Mogher KHAMAISI ◽  
Oren KAVEL ◽  
Moti ROSENSTOCK ◽  
Michal PORAT ◽  
Michal YULI ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Insulin Secretion ◽  
Insulin Action ◽  
Impaired Insulin ◽  
Insulin Responsiveness

Decreased cellular GSH content is a common finding in experimental and human diabetes, in which increased oxidative stress appears to occur. Oxidative stress has been suggested to play a causative role in the development of impaired insulin action on adipose tissue and skeletal muscle. In this study we undertook to investigate the potential of GSH depletion to induce insulin resistance, by utilizing the GSH synthesis inhibitor, L-buthionine-[S,R]-sulfoximine (BSO). GSH depletion (20-80% in various tissues), was achieved in vivo by treating rats for 20 days with BSO, and in vitro (80%) by treating 3T3-L1 adipocytes with BSO for 18 h. No demonstrable change in the GSH/GSSG ratio was observed following BSO treatment. GSH depletion was progressively associated with abnormal glucose tolerance test, which could not be attributed to impaired insulin secretion. Skeletal muscle insulin responsiveness was unaffected by GSH depletion, based on normal glucose response to exogenous insulin, 2-deoxyglucose uptake measurements in isolated soleus muscle, and on normal skeletal muscle expression of GLUT4 protein. Adipocyte insulin responsiveness in vitro was assessed in 3T3-L1 adipocytes, which displayed decreased insulin-stimulated tyrosine phosphorylation of insulin-receptor-substrate proteins and of the insulin receptor, but exaggerated protein kinase B phosphorylation. However, insulin-stimulated glucose uptake was unaffected by GSH depletion. In accordance, normal adipose tissue insulin sensitivity was observed in BSO-treated rats in vivo, as demonstrated by normal inhibition of circulating non-esterified fatty acid levels by endogenous insulin secretion. In conclusion, GSH depletion by BSO results in impaired glucose tolerance, but preserved adipocyte and skeletal muscle insulin responsiveness. This suggests that alternative oxidation-borne factors mediate the induction of peripheral insulin resistance by oxidative stress.

Intestinal calcium transport in the spontaneously hypertensive rat: response to calcium depletion

1986 ◽  
Vol 250 (4) ◽  
pp. G412-G419
Author(s):  
H. P. Schedl ◽  
D. L. Miller ◽  
R. L. Horst ◽  
H. D. Wilson ◽  
K. Natarajan ◽  
...  
Keyword(s):  
Vitamin D ◽  
Small Intestine ◽  
Calcium Transport ◽  
Spontaneously Hypertensive Rat ◽  
Calcium Depletion ◽  
Spontaneously Hypertensive ◽  
Distal Small Intestine ◽  
Wistar Kyoto

We previously found intestinal Ca2+ transport to be lower in the spontaneously hypertensive (SH) as compared with the Wistar-Kyoto control (WKY) rat. These animals were fed a relatively high (1%) Ca2+ diet, and the concentration of 1 alpha,25-dihydroxycholecalciferol [1 alpha,25(OH)2D3] in serum was the same in both groups. In the present experiment we tested the possibility that the lower Ca2+ transport in the SH rat was the result of unresponsiveness to 1 alpha,25(OH)2D3. We fed diets high and low in Ca2+ and measured serum 1 alpha,25(OH)2D3 and Ca2+ transport. Serum 1 alpha,25(OH)2D3 increased in response to Ca2+ depletion at both 5 and 12 wk in both the WKY and SH rat. With high-Ca2+ diet, Ca2+ transport was lower in SH than in WKY when studied 1) in vitro in duodenum at 5 wk of age, and 2) in vivo in proximal and distal small intestine at 12 wk of age. Ca2+ transport increased in SH in response to Ca2+ depletion, but not in WKY, except in distal small intestine in vivo at 12 wk. In summary, although Ca2+ transport is lower in the SH as compared with the WKY rat when vitamin D activity is basal through feeding a high-Ca2+ diet, Ca2+ transport increases in the SH rat in response to the increase in 1 alpha,25(OH)2D3 produced by feeding a low-Ca2+ diet. We conclude that 1) the vitamin D-regulated component of mediated Ca2+ transport is intact in the SH rat and is unrelated to hypertension, and 2) mediated Ca2+ transport under basal conditions, i.e., nonvitamin D-regulated, differs in the SH and WKY rats and may be related to hypertension.

scholarly journals Chronic in vivo or acute in vitro resveratrol attenuates endothelium-dependent cyclooxygenase-mediated contractile signaling in hypertensive rat carotid artery

2016 ◽  
Vol 120 (10) ◽  
pp. 1141-1150 ◽  
Author(s):  
Steven G. Denniss ◽  
Rebecca J. Ford ◽  
Christopher S. Smith ◽  
Andrew J. Jeffery ◽  
James W. E. Rush
Keyword(s):  
Carotid Artery ◽  
Day Treatment ◽  
Spontaneously Hypertensive ◽  
Compound C ◽  
Tp Receptor ◽  
Wistar Kyoto ◽  
Amp Activated Protein Kinase ◽  
Endothelium Dependent Relaxation

Exaggerated cyclooxygenase (COX) and thromboxane-prostanoid (TP) receptor-mediated endothelium-dependent contraction can contribute to endothelial dysfunction. This study examined the effect of resveratrol (RSV) on endothelium-dependent contraction and cell signaling in the common carotid artery (CCA) from spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). Acetylcholine (Ach)-stimulated endothelium-dependent nitric oxide synthase (NOS)-mediated relaxation in precontracted SHR CCA was impaired (maximum 73 ± 6% vs. 87 ± 5% in WKY) ( P < 0.05) by competitive COX-mediated contraction. Chronic (28-day) treatment in vivo (drinking water) with a ∼0.075 mg·kg−1·day−1 RSV dose affected neither endothelium-dependent relaxation nor endothelium-dependent contraction and associated prostaglandin (PG) production evaluated in non-precontracted NOS-blocked CCA. In contrast, a chronic ∼7.5 mg·kg−1·day−1 RSV dose improved endothelium-dependent relaxation (94 ± 6%) and attenuated endothelium-dependent contraction (58 ± 4% vs. 73 ± 5% in No-RSV) and PG production (183 ± 43 vs. 519 ± 93 pg/ml) in SHR CCA, while U46619-stimulated TP receptor-mediated contraction was unaffected. In separate acute in vitro experiments, 20-μM RSV preincubation attenuated endothelium-dependent contraction (6 ± 4% vs. 62 ± 2% in No Drug) and PG production (121 ± 15 vs. 491 ± 93 pg/ml) and attenuated U46619-stimulated contraction (134 ± 5% vs. 171 ± 4%) in non-precontracted NOS-blocked SHR CCA. Compound C, a known AMP-activated protein kinase (AMPK) inhibitor, did not prevent the RSV attenuating effect on Ach- and U46619 -stimulated contraction but did prevent the RSV attenuating effect on PG production (414 ± 58 pg/ml). These data demonstrate that RSV can attenuate endothelium-dependent contraction both by suppressing arterial wall PG production, which may be partially mediated by AMPK, and by TP receptor hyporesponsiveness, which does not appear to be mediated by AMPK.

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