Improvement of insulin resistance by troglitazone ameliorates cardiac sympathetic nervous dysfunction in patients with essential hypertension

Watanabe, Kentaro; Komatsu, Jiroh; Kurata, Makoto; Inaba, Shinji; Ikeda, Shuntaro; Sueda, Shozo; Suzuki, Jun; Kohara, Katsuhiko; Hamada, Mareomi

doi:10.1097/00004872-200409000-00021

Cited by 12 publications

(6 citation statements)

References 32 publications

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“…Studies in both animal models of hypertension and in humans with insulin resistance suggest that treatment with thiazolidinediones reduces urinary catecholamines, skin sympathetic nerve activity, and cardiac sympathetic nervous system function (55,59,61). The contribution of sympathetic activation to SLE hypertension has not been previously examined.…”

Section: Discussionmentioning

confidence: 99%

Rosiglitazone decreases blood pressure and renal injury in a female mouse model of systemic lupus erythematosus

Venegas-Pont

Sartori‐Valinotti

Maric

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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-Women with systemic lupus erythematosus (SLE) exhibit a high prevalence of hypertension and renal injury. Rosiglitazone (Rosi), a peroxisome proliferator activator receptor gamma (PPAR␥) agonist, has renal protective and antihypertensive effects. We tested whether Rosi ameliorates hypertension and renal injury in a female mouse model of SLE (NZBWF1). Thirty-week-old SLE and control (NZW/LacJ) mice (n Ն 6/group) were fed Rosi (5 mg ⅐ kg Ϫ1 ⅐ day Ϫ1 in standard chow) or standard chow for 4 wk. SLE mice had increased blood pressure (BP in mmHg) compared with controls (139 Ϯ 4 vs. 111 Ϯ 4, P Ͻ 0.05). Rosi treatment lowered BP in SLE mice (127 Ϯ 4, P Ͻ 0.05) but not in controls (111 Ϯ 4). Urinary albumin (g/mg creatinine) was increased in SLE mice compared with controls (12,396 Ϯ 6,525 vs. 50 Ϯ 6) and reduced with Rosi treatment (148 Ϯ 117). Glomerulosclerosis (% of glomeruli with sclerosis) was reduced in Rosi-treated SLE mice (4.2 Ϯ 1.6 vs. 0.4 Ϯ 0.3, P Ͻ 0.05). Renal monocyte/ macrophage numbers (cell number/1,320 points counted) were reduced in SLE mice treated with Rosi (32.6 Ϯ 11.0 vs. 10.6 Ϯ 3.6, P Ͻ 0.05) but unchanged in controls (3.7 Ϯ 1.6 vs. 3.7 Ϯ 2.0). Renal osteopontin expression, a cytokine-regulating macrophage recruitment, was reduced in Rosi-treated SLE mice. Urinary endothelin (in pg/mg creatinine) was increased in SLE mice compared with controls (1.9 Ϯ 0.59 vs. 0.6 Ϯ 0.04, P Ͻ 0.05) and reduced in SLE mice treated with Rosi (0.8 Ϯ 0.11, P Ͻ 0.05). PPAR␥ protein expression in the renal cortex was significantly lower in SLE mice compared with controls and was unaffected by Rosi. These data suggest that Rosi may be an important therapeutic option for the treatment of SLE hypertension and renal injury. lupus; inflammation; endothelin; glomerulosclerosis; proliferator activated receptor gamma SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) is a chronic autoimmune inflammatory disorder that has a strong predilection for women during their reproductive years. The hallmark of the disease is the production of autoantibodies such as antinuclear antibodies, and more specifically anti-double-stranded DNA (antidsDNA) antibodies. Accumulating evidence indicates that the major cause of death among patients with SLE is cardiovascular disease (17,22,23,26). Indeed, studies have reported that women with SLE are at a 50-fold greater risk for developing cardiovascular disease independent of traditional Framingham Heart Study risk factors (35). One of the major factors contributing to the progression of cardiovascular disease is increased arterial pressure. Importantly, SLE is associated with a high incidence of hypertension (1, 41, 56).The kidneys are prominently affected during SLE in the form of immune complex glomerulonephritis. This occurs in greater than 50% of patients with SLE (18) and is caused, in part, by circulating anti-dsDNA antibody-mediated formation of immune complexes (51). Few advances have been made toward the treatment of SLE and the associated nephritis and hypertension in the past 40 years. Patients with SL...

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Section: Discussionmentioning

confidence: 99%

Rosiglitazone decreases blood pressure and renal injury in a female mouse model of systemic lupus erythematosus

Venegas-Pont

Sartori‐Valinotti

Maric

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Heart-rate variability studies suggest that insulin resistance may be responsible for early derangements of cardiac autonomic tone, characterized by increased low-to high-frequency ratio or sympathovagal balance, independent of obesity [ 32 ]. Six months of treatment with an insulin-sensitizing agent belonging to the thiazolidinedione group exerted signifi cant cardiac sympathoinhibitory effects by reducing the uptake of norepinephrine from cardiac nerve terminals and increasing its myocardial tissue clearance [ 33 ].…”

Section: Hyperinsulinemia/insulin Resistancementioning

confidence: 99%

Mediators of sympathetic activation in metabolic syndrome obesity

Straznicky

Eikelis²,

Lambert³

et al. 2008

Current Science Inc

118

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The metabolic syndrome represents a major public health burden because of its high prevalence in the general population and its association with cardiovascular disease and type 2 diabetes. Accumulated evidence based on biochemical, neurophysiologic, and indirect measurements of autonomic activity indicate that visceral obesity and the metabolic syndrome are associated with enhanced sympathetic neural drive and vagal impairment. The mechanisms linking metabolic syndrome with sympathetic activation are complex and not completely understood, and cause-effect relationships need further clarification from prospective trials. Components of the metabolic syndrome that may directly or indirectly enhance sympathetic drive include hyperinsulinemia, leptin, nonesterified fatty acids, proinflammatory cytokines, angiotensinogen, baroreflex impairment, and obstructive sleep apnea. beta-Adrenoceptor polymorphisms have also been associated with adrenoceptor desensitization, increased adiposity, insulin resistance, and enhanced sympathetic activity. Because chronic sympathetic activation contributes to hypertension and its target-organ damage, sympathoinhibition remains an important goal in the therapeutic management of the metabolic syndrome.

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“…In the study from Yosefy et al [117] the observed reductions in office BP and plasma insulin in the rosiglitazone group were accompanied with a significant decline in sympathetic skin activity, measured as sympathetic skin potentials by computerised electromyography device, whereas in the glibenclamide group, apart from SBP and plasma insulin elevation an augmentation of skin sympathetic activity was documented. Finally, in the mentioned above study of Watanabe et al [84], along with clinic BP reduction, cardiac sympathetic nervous dysfunction (evaluated using the heartto-mediastinum ratio and mean washout rate measured by 123I-meta-iodobenzylguanidine (MIBG) cardiac imaging) was significantly improved in the troglitazone group, and these changes were significantly correlated with the observed change in IR.…”

Section: Ii) Studies On Sympathetic Nervous System Activitymentioning

confidence: 84%

“…The only study reporting an effect of troglitazone on BP since then is a recently published one, in which 34 patients with mild essential hypertension were treated for 6 months either with antihypertensive drugs or with antihypertensive drugs plus 400 mg of troglitazone [84]. In the troglitazone-treated group clinic BP presented a significant fall of 7.4±5.9/4.8±4.7, whereas in the other group BP remained practically unchanged.…”

Section: Studies With Troglitazonementioning

confidence: 99%

PPARγ Agonists: Beneficial Effect on Blood Pressure Beyond Glycemic Control?

Sarafidis¹,

Lasaridis

2006

CHYR

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The Metabolic or Insulin Resistance Syndrome is a cluster of cardiovascular risk factors, such as type 2 diabetes mellitus, hypertension, central obesity, dyslipidaemia, and other disorders, which have been proposed to be secondary to insulin resistance. A number of possible mechanisms linking insulin resistance and compensatory hyperinsulinemia with hypertension have been described, such as renal sodium reabsorption enhancement, sympathetic nervous system activation, or blunted insulin-mediated vasodilatation due to endothelial dysfunction. PPAR agonists or thiazolidine-diones (TZDs) are a class of oral antihyperglycemic agents that act through improvement of insulin sensitivity. Apart from their action on glycemic control, in several studies TZDs have been also reported to exert beneficial effects on other parameters of the metabolic syndrome. This review summarizes the literature data on the effect of troglitazone, pioglitazone and rosiglitazone on blood pressure (BP), which derive from animal and human studies that were either specifically designed to determine the effect of TZDs on BP or just examined BP levels among other parameters. In addition, it presents in vitro and in vivo evidence about various TZDs actions on the cardiovascular system that could positively influence BP, representing therefore possible mechanisms of this BP amelioration.

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Improvement of insulin resistance by troglitazone ameliorates cardiac sympathetic nervous dysfunction in patients with essential hypertension

Abstract: Troglitazone had a beneficial effect on cardiac sympathetic nervous function through a decrease in insulin resistance in patients with essential hypertension.

Cited by 12 publications

References 32 publications

Rosiglitazone decreases blood pressure and renal injury in a female mouse model of systemic lupus erythematosus

Rosiglitazone decreases blood pressure and renal injury in a female mouse model of systemic lupus erythematosus

Mediators of sympathetic activation in metabolic syndrome obesity

PPARγ Agonists: Beneficial Effect on Blood Pressure Beyond Glycemic Control?

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Improvement of insulin resistance by troglitazone ameliorates cardiac sympathetic nervous dysfunction in patients with essential hypertension

Abstract: Troglitazone had a beneficial effect on cardiac sympathetic nervous function through a decrease in insulin resistance in patients with essential hypertension.

Cited by 12 publications

References 32 publications

Rosiglitazone decreases blood pressure and renal injury in a female mouse model of systemic lupus erythematosus

Rosiglitazone decreases blood pressure and renal injury in a female mouse model of systemic lupus erythematosus

Mediators of sympathetic activation in metabolic syndrome obesity

PPAR&#947; Agonists: Beneficial Effect on Blood Pressure Beyond Glycemic Control?

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PPARγ Agonists: Beneficial Effect on Blood Pressure Beyond Glycemic Control?