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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Consumption of diets rich in fats or sugars is correlated with the onset of insulin resistance and hypertension in rats. In the present study, rats were fed diets that induce hypertension; 50% of the rats were also treated with pioglitazone, a thiazolidinedione derivative that sensitizes target tissues to insulin and decreases plasma insulin concentration in insulin-resistant animals. Pioglitazone treatment prevented the development of hypertension and reduced plasma insulin concentration by 70% and 37% in rats fed a high-fat or glucose diet, respectively (P < .05 compared with rats fed the same diet without pioglitazone). In rats fed a control diet, neither insulin nor blood pressure (BP) was affected by pioglitazone treatment. The effect of pioglitazone on insulin and BP could not be attributed to a reduction in body weight, since pioglitazone increased the weight gain of rats fed the high-fat or glucose diet. These findings suggest that in rats fed a diet high in fat or glucose, treatment with pioglitazone maintains plasma insulin concentration and BP at control levels, regardless of body weight.
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PMID:Pioglitazone attenuates diet-induced hypertension in rats. 766 81

Hypertension is often associated with insulin resistance, and several chemically diverse agents that increase insulin sensitivity attenuate the development of experimental hypertension. We undertook the present study to determine whether attenuation of hypertension by pioglitazone, a thiazolidinedione derivative that increases insulin sensitivity without increasing insulin secretion, is specifically related to its effect on insulin-mediated glucose uptake. Pioglitazone administered daily by oral gavage (20 mg/kg per day) for 3 weeks attenuated the development of hypertension in both the Dahl salt-sensitive (DS) rat (an insulin-resistant model of hypertension) and the one-kidney, one clip rat (a model of hypertension not associated with insulin resistance). Based on euglycemic insulin clamp studies in conscious animals, the glucose clearance rate was increased (P < .05) in pioglitazone-treated DS rats (36 +/- 3 mg/kg per minute) compared with control DS rats (27 +/- 1 mg/kg per minute). However, pioglitazone did not affect the glucose clearance rate in one-kidney, one clip hypertensive rats. Metformin, an unrelated agent that also improves glucose tolerance, had no significant effect on blood pressure or glucose clearance rate in either DS or one-kidney, one clip rats. Thus, the hypotensive effect of pioglitazone is not invariably associated with its capacity to improve insulin-induced glucose utilization.
Hypertension 1994 Jul
PMID:Antihypertensive effect of pioglitazone is not invariably associated with increased insulin sensitivity. 802 Sep 98

Pioglitazone, an insulin-sensitizing, antidiabetic agent, has blood pressure-lowering effects in insulin-resistant hypertensive rats and attenuates growth factor-induced increases of intracellular Ca2+ in rat aortic vascular smooth muscle cells. To determine whether modulation of voltage-dependent Ca2+ channels plays a role in this association, we investigated the effects of pioglitazone on voltage-dependent current in cultured rat aortic (a7r5) and freshly dissociated rat tail artery vascular smooth muscle cells. Both cell types were studied with whole-cell patch-clamp techniques. Current through L-type Ca2+ channels was elicited with a voltage ramp in the presence of Ba2+ substituted for Ca2+. T-type Ca2+ current was studied using a two-pulse protocol that enabled the isolation of transient current. In a7r5 vascular smooth muscle cells, 2-minute application of pioglitazone (5 and 10 mumol/L) reduced L-type current by 7.9 +/- 1.0% (n = 8) (mean +/- SEM, number of cells) and 14.5 +/- 3.0% (n = 9) (P < .01, two-tailed paired t test), respectively. In contrast, 2-minute application of pioglitazone had no significant effect on T-type Ca2+ current. In freshly dissociated tail artery vascular smooth muscle cells, 2-minute application of 10 mumol/L pioglitazone had an insignificant effect (4.8 +/- 5.6% reduction); however, 25 mumol/L pioglitazone reduced L-type current by 27.3 +/- 7.2% (n = 5) (P < .01). Two-minute application of 0.1% or 0.2% dimethyl sulfoxide (vehicle) alone had no significant effects on currents in either type of vascular smooth muscle cell.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1994 Aug
PMID:Effects of pioglitazone on calcium channels in vascular smooth muscle. 803 40

Hypertension is frequently associated with insulin resistance. We evaluated the effects of pioglitazone, an agent that increases insulin sensitivity, on the development of hypertension in the Dahl salt-sensitive (Dahl-S) rat and in the one-kidney, one-clip Sprague-Dawley rat. We also evaluated the effects of pioglitazone on growth of cultured preglomerular renal arteriolar smooth muscle cells. In Dahl-S rats fed a 3% NaCl diet, tail systolic blood pressures and direct arterial pressures were lower (P < 0.05) in pioglitazone-treated (20 mg/kg daily by gavage for 3 wk) than in control rats (n = 10 rats/group). In one-kidney, one-clip Sprague-Dawley rats, systolic blood pressures were also lower in pioglitazone-treated animals (P < 0.0001). In vitro, proliferation of arteriolar smooth muscle cells was stimulated (P < 0.01) by insulin, epidermal growth factor (EGF), and fetal calf serum (FCS); pioglitazone (5 microM) reversibly inhibited (P < 0.01) insulin-, EGF-, and FCS-induced proliferation. Pioglitazone (0.01-100 microM) also inhibited insulin- (1 mU/ml), EGF- (100 ng/ml), and 5% FCS-induced [3H]thymidine incorporation in a concentration-dependent manner (P < 0.01). Thus pioglitazone attenuated the development of hypertension in the Dahl-S rat and the one-kidney, one-clip rat. The ability of pioglitazone to inhibit growth of vascular smooth muscle may contribute to its hypotensive effect.
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PMID:Pioglitazone attenuates hypertension and inhibits growth of renal arteriolar smooth muscle in rats. 823 39

Pioglitazone (a thiazolidinedione derivative) increases insulin sensitivity and prevents hypertension in the Dahl-salt-sensitive (S) rat. The present study was undertaken to determine if pioglitazone modulates pressor responsiveness to vasoactive agents, both in vivo and in vitro. In vivo, pretreatment with pioglitazone inhibited (P < 0.02) pressor responses to both norepinephrine and angiotensin II in conscious Dahl-S, but not in Sprague-Dawley rats. In vitro, pioglitazone augmented the capacity of insulin to inhibit pressor responses of strips of thoracic aortas to norepinephrine, but not to angiotensin. Additionally, in vitro, incubation with insulin plus pioglitazone augmented acetylcholine-induced, but not nitroprusside-induced vasodilation. Pioglitazone pretreatment increased (P < 0.001) in vitro insulin-stimulated glucose uptake in adipose tissue, but not in thoracic aortas of Dahl-S. We hypothesize that pioglitazone attenuates hypertension by modulating the effects of insulin on vascular function, resulting in both blunted vasoconstriction and augmented acetylcholine-induced vasodilation. These alterations are not accounted for by an effect of pioglitazone on glucose uptake by vascular smooth muscle.
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PMID:Effect of pioglitazone on vascular reactivity in vivo and in vitro. 878 Feb 34

Although an improvement of insulin sensitivity has been shown to be a new therapeutic approach for treating diabetes mellitus, details of effects of this treatment on the cardiovascular system and possible renal complications remain unknown. In the present study, we investigated the effects of a thiazolidine derivative, pioglitazone, and examined the insulin-sensitizing action on blood pressure, nephropathy, and vascular changes in genetically obese diabetic Wistar fatty (WF) rats. Pioglitazone (3 mg.kg-1.day-1) was orally administered for 13 wk starting at the age of 5 wk, and the results were compared with those of vehicle-treated WF rats. At the age of 18 wk, vehicle-treated WF rats were associated with mild hypertension, nephropathy with proteinuria histological glomerular injury, and renal arteriolosclerosis in addition to hyperglycemia, hyperinsulinemia, and hyperlipidemia. Treatment with pioglitazone significantly improved glucose and lipid metabolism. In addition, it lowered blood pressure, decreased proteinuria, and prevented glomerular injury, renal arteriolosclerosis, and aortic medial wall thickening, whereas body weight, food intake, sodium balance, and urinary norepinephrine excretion were significantly increased. These results suggest that the insulin-sensitizing agent pioglitazone is effective in correcting not only glucose and lipid metabolism but also cardiovascular and renal complications in non-insulin-dependent diabetes mellitus.
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PMID:Antihypertensive and vasculo- and renoprotective effects of pioglitazone in genetically obese diabetic rats. 922 42

We examined the effect of pioglitazone, a thiazolidinedione derivative that increases insulin sensitivity without increasing insulin secretion, on the development and maintenance of hypertension in sucrose-fed SHR. Nine-week-old male SHR received 12% sucrose dissolved in tap water as drinking water. For 5 weeks, half of the rats were given regular rat chow, and the rest were fed with rat chow containing 0.03% pioglitazone. In week 6, blood glucose and plasma insulin levels were examined before and after oral glucose administration by gavage. Sucrose treatment elicited a significant elevation of systolic blood pressure 3 weeks after the beginning of treatment; pioglitazone treatment attenuated this elevation. The insulin resistance and hyperinsulinemia observed in sucrose-fed SHR were prevented by pioglitazone treatment. Pioglitazone treatment also significantly reduced the urinary excretion of catecholamines and plasma renin activity, both of which were significantly greater in sucrose-fed SHR than in control SHR. Along with improving insulin sensitivity, pioglitazone treatment also attenuated the development of hypertension in SHR fed the regular rat chow, but not in WKY rats. These results indicate that insulin resistance and hyperinsulinemia play an important role in the development of hypertension in SHR probably through the activation of the renin-angiotensin system and sympathetic nervous outflow. This study also shows that chronic sucrose treatment exacerbated the development of hypertension through these mechanisms, precipitating insulin resistance.
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PMID:Reduction of insulin resistance attenuates the development of hypertension in sucrose-fed SHR. 924 72

Subjects with hypertension are hyperinsulinemic and resistant to insulin-stimulated glucose uptake. A similar paradigm is found in the spontaneously hypertensive rat (SHR). These findings suggest the possibility that insulin resistance and hyperinsulinemia may play an important role in blood pressure regulation. Pioglitazone, a thiazolidinedione derivative, sensitizes target tissues to insulin and decreases hyperglycemia and hyperinsulinemia in various insulin-resistant animals. The purpose of this study was to assess the influence of pioglitazone administration on pre- and postprandial glucose and insulin concentrations and determine whether changes in beta-cell secretion resulted in any change in blood pressure measurements. Twelve SHR were fed custom diets ad libitum, six with and six without pioglitazone (20 mg/kg chow). Fasting and postprandial glucose levels were unaltered by pioglitazone treatment. Fasting insulin concentrations were similar at week 1, but were significantly lower (P < .01) in the pioglitazone group at weeks 3 (1.89 +/- 0.3 v7.94 +/- 1.5 ng/mL) and 4 (4.5 +/- 1.4 v9.1 +/- 0.7 ng/mL), compared with the control group. Pioglitazone also significantly (P < .01) lowered postprandial insulin concentrations after an oral glucose challenge. Systolic, mean, and diastolic blood pressures were significantly lower (P < .01), 177 +/- 3 v190 +/- 4.7 mm Hg, 162 +/- 2.1 v175 +/- 5.9 mm Hg, and 156 +/-2.1 v168 +/- 6.2 mm Hg, respectively, in the animals receiving pioglitazone versus the control group. Heart rate, body weight, serum cholesterol, and triglyceride levels were comparable between the two groups. In conclusion, pioglitazone significantly decreased fasting and postprandial insulin concentrations and effectively lowered blood pressure in the SHR.
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PMID:Pioglitazone attenuates basal and postprandial insulin concentrations and blood pressure in the spontaneously hypertensive rat. 1082 38

Peroxisome proliferator-activated receptor-gamma (PPARgamma) ligands are widely used in patients with insulin resistance and diabetes. Because coronary artery disease is a major complication for such patients, it is important to determine the effects of PPARgamma activation on arteriosclerosis. Long-term inhibition of endothelial NO synthesis by administration of N(omega)-nitro-L-arginine methyl ester (L-NAME) to rats induces coronary vascular inflammation (monocyte infiltration, monocyte chemoattractant protein-1 [MCP-1] expression) and subsequent arteriosclerosis. We examined the effects of pioglitazone (a PPARgamma ligand) in this rat model to determine whether PPARgamma activation with pioglitazone inhibits arteriosclerosis by its indirect effects on metabolic conditions or by direct effects on the cells participating to the pathogenesis of arteriosclerosis. We found that pioglitazone did not affect metabolic states, systolic blood pressure, or serum NO levels, but did prevent the L-NAME-induced coronary inflammation and arteriosclerosis. Pioglitazone did not reduce local expression of MCP-1 but markedly attenuated increased expression of the MCP-1 receptor C-C chemokine receptor 2 (CCR2) in lesional and circulating monocytes. PPARgamma activation with pioglitazone prevented coronary arteriosclerosis, possibly by its antiinflammatory effects (downregulation of CCR2 in circulating monocytes). Inhibition of the CCR2-mediated inflammation may represent novel antiinflammatory actions of pioglitazone beyond improvement of metabolic state.
Hypertension 2002 Nov
PMID:Antiinflammatory and antiarteriosclerotic effects of pioglitazone. 1241 63

Hypertension is often associated with insulin resistance, dyslipidemia and obesity, which indicate a prediabetic state and increased risk of cardiovascular disease. Pioglitazone treatment of patients with type 2 diabetes reduces insulin resistance and improves lipid profiles. The present double-blind placebo-controlled study is the first study to report effects of pioglitazone in non-diabetic patients with arterial hypertension. Following a one week run-in, 60 patients were randomized to receive either pioglitazone (45 mg/day) or placebo for 16 weeks. Insulin sensitivity (M-value) increased by 1.2 +/- 1.7 mg/min/kg with pioglitazone compared with 0.4 +/- 1.4 mg/min/kg (P = 0.022) with placebo. HOMA index was decreased (-22.5 +/- 45.8) by pioglitazone but not by placebo (+0.8 +/- 26.5; P < 0.001). Decreases in fasting insulin and glucose were significantly (P = 0.002 and P = 0.004, respectively) greater with pioglitazone than placebo. Body weight did not change significantly with either treatment. HDL-cholesterol was increased and apolipoprotein B was decreased to a significantly greater extent with pioglitazone. There was a significantly (P = 0.016) greater decrease from baseline in diastolic blood pressure with pioglitazone. These changes would suggest improved glucose metabolism and a possible reduction in risk of cardiovascular disease with pioglitazone treatment of non-diabetic patients with arterial hypertension.
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PMID:Effects of pioglitazone in nondiabetic patients with arterial hypertension: a double-blind, placebo-controlled study. 1246 45


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