Angiotensin receptor blockers improve insulin signaling and prevent microvascular rarefaction in the skeletal muscle of spontaneously hypertensive rats

Rizzoni, Damiano; Pasini, Evasio; Flati, Vincenzo; Rodella, Luigi Fabrizio; Paiardi, Silvia; Assanelli, Deodato; Ciuceis, Carolina De; Porteri, Enzo; Boari, Gianluca E.M.; Rezzani, Rita; Speca, Silvia; Martinotti, Stefano; Toniato, E; Platto, Caterina; Agabiti‐Rosei, Enrico

doi:10.1097/hjh.0b013e328304b060

Cited by 24 publications

(19 citation statements)

References 26 publications

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“…In a study in 70 hypertensive patients, losartan also reduced vascular rarefaction and hypertrophy and improved insulin sensitivity after 3 years of treatment, compared with the b-blocker atenolol. 101 In line, in SHR, the angiotensin II type 1 receptor blocker olmesartan improved insulin signalling and prevented microvascular rarefaction in the skeletal muscle; 102 thus, theoretically, restored insulin signalling may also contribute to vascular proliferation and angiogenesis.…”

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confidence: 92%

Angiogenesis and hypertension: an update

2009

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The purpose of this review is to provide a basic understanding of the important relationship between microvascular remodelling, angiogenesis and hypertension, that is, provide an overview of recent experimental and clinical evidence from anti-hypertensive and pro-and anti-angiogenic therapy with respect to hypertension and microvascular structure. Microvascular rarefaction, that is, a loss of terminal arterioles and capillaries, is found in most forms of human and experimental arterial hypertension. This further increases peripheral resistance, and aggravates hypertension and hypertension-induced target organ damage. In some cases with a genetic predisposition, hypertension is preceded by a loss of microvessels. Therefore, new therapies aimed at reversing microvascular rarefaction potentially represent candidate treatments of hypertension. The microvasculature is formed by the continuous balance between de novo angiogenesis and microvascular regression. Imbalanced angiogenesis, in addition to functional shut-off of blood flow, contributes to microvascular rarefaction. Numerous clinical trials assessing anti-angiogenic agents in cancer patients show that this therapy leads to microvascular rarefaction and causes or aggravates hypertension. The development of specific pro-angiogenic treatment to correct hypertension or ischaemic disorders, however, it is still in its infancy. On the other hand, long-term treatment by classic anti-hypertensive therapies that present vasodilator activity can correct for hypertension-associated rarefaction in man.

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confidence: 92%

Angiogenesis and hypertension: an update

2009

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“…Insulin resistance in skeletal muscle is thought to contribute to the development of hypertension. [26][27][28][29][30][31] On the other hand, recent studies have shown that IR can occur separately in the liver and in skeletal muscles. 32 Current clinical indexes of insulin sensitivity (IS) are not specific to IS in the liver or that in the skeletal muscle.…”

Section: Introductionmentioning

confidence: 99%

Matsuda–DeFronzo insulin sensitivity index is a better predictor than HOMA-IR of hypertension in Japanese: the Tanno–Sobetsu study

et al. 2011

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Here we examined whether the Matsuda-DeFronzo insulin sensitivity index (ISI-M) is more efficient than the homeostasis model assessment of insulin resistance (HOMA-IR) for assessing risk of hypertension. Cross-sectional and longitudinal analyses were conducted using normotensive subjects who were selected among 1399 subjects in the Tanno-Sobetsu cohort. In the cross-sectional analysis (n ¼ 740), blood pressure (BP) level was correlated with HOMA-IR and with ISI-M, but correlation coefficients indicate a tighter correlation with ISI-M. Multiple linear regression analysis adjusted by age, sex, body mass index (BMI) and serum triglyceride level (TG) showed contribution of ISI-M and fasting plasma glucose, but not of HOMA-IR. In the longitudinal analysis (n ¼ 607), 241 subjects (39.7%) developed hypertension during a 10-year follow-up period, and multiple logistic regression indicated that age, TG, systolic BP and ISI-M, but not HOMA-IR, were associated with development of hypertension. In subjects o60 years old, odds ratio of new-onset hypertension was higher in the low ISI-M group (ISI-M, less than the median) than in the high ISI-M group for any tertile of BMI. In conclusion, ISI-M is a better predictor of hypertension than is HOMA-IR. Non-hepatic IR may be a determinant, which is independent of TG, BP level and BMI, of the development of hypertension.

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“…Indeed, we found that local administration of Ang II into the gastrocnemius muscle by microdialysis markedly decreased local blood flow in lean and obese subjects [63]. In line, chronic RAS blockade increased postprandial forearm blood flow in subjects with type 2 diabetes [64], and both acute and chronic RAS blockade prevented or improved skeletal muscle microvascular dysfunction in rats [65,66,67]. However, we did not find an increase in basal and insulin-stimulated total forearm blood flow after 2 weeks ACEi treatment in obese insulin resistant subjects [54].…”

Section: The Renin-angiotensin System and Skeletal Muscle Functionmentioning

confidence: 68%

The Renin-Angiotensin System in the Pathophysiology of Type 2 Diabetes

Goossens¹

2012

Obes Facts

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Increased activation of the renin-angiotensin system (RAS) has been related to cardiovascular disease and type 2 diabetes mellitus. Most randomized clinical trials have demonstrated that RAS blockade reduces the incidence of type 2 diabetes, which has been explained by improved insulin secretion and insulin sensitivity. In this review, an overview of the mechanisms that may underlie the association between the RAS and type 2 diabetes will be provided, with focus on skeletal muscle and adipose tissue function. This will include discussion of several human studies performed in our laboratory to investigate the metabolic and hemodynamic effects of the RAS, combining in vivo measurements of whole-body and tissue metabolism with molecular and immunohistochemical approaches. Available data suggest that the detrimental effects of the RAS on insulin secretion are mediated by a reduction in pancreatic blood flow and induction of islet fibrosis, oxidative stress as well as inflammation, whereas both impaired skeletal muscle function and adipose tissue dysfunction may underlie RAS-induced insulin resistance. Thus, although future studies in humans are warranted, current evidence supports that targeting the RAS in intervention studies may improve metabolic and cardiovascular function in conditions of insulin resistance like obesity and type 2 diabetes.

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Angiotensin receptor blockers improve insulin signaling and prevent microvascular rarefaction in the skeletal muscle of spontaneously hypertensive rats

Cited by 24 publications

References 26 publications

Angiogenesis and hypertension: an update

Angiogenesis and hypertension: an update

Matsuda–DeFronzo insulin sensitivity index is a better predictor than HOMA-IR of hypertension in Japanese: the Tanno–Sobetsu study

The Renin-Angiotensin System in the Pathophysiology of Type 2 Diabetes

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