Potential for Endothelin‐1‐mediated Impairment of Contractile Activity in Hypertension

Kolka, Cathryn M.; Rattigan, Stephen; Richards, Stephen M.; Clark, Michael G.

doi:10.1111/j.1440-1681.2007.04575.x

Cited by 3 publications

(2 citation statements)

References 29 publications

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“…Excessive vasoconstriction by endothelin in hypertension and the metabolic syndrome may prevent appropriate insulin-mediated haemodynamics and also impair basal metabolism [83]. Further, we have shown that high levels of endothelin-1 can also reduce exercise capacity in muscle, likely due to the fact that oxygen and fuel access to the muscle is impaired with excessive vasoconstriction [113].…”

Section: Hypertensionmentioning

confidence: 89%

The Skeletal Muscle Microvasculature and Its Effects on Metabolism

Kolka¹

2016

Microcirculation Revisited - From Molecules to Clinical Practice

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Skeletal muscle is a major metabolic organ that plays a critical role in regulating glucose homeostasis and lipid utilization. Impaired muscle metabolic response is evident in diseases such as diabetes, obesity and cardiovascular diseases, and is also often associated with microvascular dysfunction. Here, we investigate the changes that can occur in the muscle microvasculature and the profound impact they can have on metabolism. Under basal conditions, vasoactive compounds are able to affect metabolism in muscle by providing more glucose and oxygen to resting muscle. Insulin and exercise increase the perfusion of muscle, and thus provide more microvascular surface area, increasing the delivery of these metabolites to muscle. Endothelial dysfunction can therefore impair the delivery of oxygen, glucose and hormones to muscle, both through effects on blood flow distribution and the transport of these factors across the endothelium, leading to a decrease in oxygen consumption and glucose metabolism. Obesity and diabetes are associated with endothelial dysfunction and are accompanied by underlying changes in metabolism and reductions in insulin sensitivity. The muscle is a highly metabolic organ, and the vasculature is essential to maintain appropriate metabolic response; therefore, the muscle microcirculation may be a target for treating metabolic disease.

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Section: Hypertensionmentioning

confidence: 89%

The Skeletal Muscle Microvasculature and Its Effects on Metabolism

Kolka¹

2016

Microcirculation Revisited - From Molecules to Clinical Practice

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“…While diabetic patients have defects in exercise capacity [2], this can be improved by either exercise training, or agents that improve insulin sensitivity. Certain hormones can be upregulated in metabolic disease, such as endothelin-1 in hypertension, and excessive levels of endothelin-1 can reduce aerobic capacity of muscle, and impair metabolism [91], most likely through impaired blood flow. Investigations are ongoing into certain drugs that are designed to mimic exercise.…”

Section: Negative or Neutral Outcomes Of Exercisementioning

confidence: 99%

Treating Diabetes with Exercise – Focus on the Microvasculature

Kolka¹

2013

J Diabetes Metab

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The rising incidence of diabetes and the associated metabolic diseases including obesity, cardiovascular disease and hypertension have led to investigation of a number of drugs to treat these diseases. However, lifestyle interventions including diet and exercise remain the first line of defense. The benefits of exercise are typically presented in terms of weight loss, improved body composition and reduced fat mass, but exercise can have many other beneficial effects. Acute effects of exercise include major changes in blood flow through active muscle, an active hyperemia that increases the delivery of oxygen to the working muscle fibers. Longer term exercise training can affect the vasculature, improving endothelial health and possibly basal metabolic rates. Further, insulin sensitivity is improved both acutely after a single bout of exercise and shows chronic effects with exercise training, effectively reducing diabetes risk. Exercisemediated improvements in endothelial function may also reduce complications associated with both diabetes and other metabolic disease. Thus, while drugs to improve microvascular function in diabetes continue to be investigated, exercise can also provide many similar benefits on endothelial function and should remain the first prescription when treating insulin resistance and diabetes. This review will investigate the effects of exercise on the blood vessel and the potential benefits of exercise on cardiovascular disease and diabetes. KeywordsExercise; Diabetes; Insulin; Muscle; Vasculature; Blood vesselsThe prevalence of diabetes has been increasing steadily in the United States and in many parts of the world. In 2010, 25.8 million individuals in the United States were diagnosed with diabetes, a figure almost double that of ten years previously [1]. Diabetes frequently occurs with other diseases, including dislipidemia, hypertension, cardiovascular disease and obesity. Exercise is also associated with significant improvements in other aspects of disease, such as the reduction of complications, associated metabolic diseases, and other risk factors [9]. The metabolic syndrome, typified by high blood pressure, high triglyceride levels, low HDLcholesterol levels, high fasting glucose, and central obesity, is recognized to predispose individuals to the development of diabetes and atherosclerosis. Interestingly, most of the criteria of the metabolic syndrome pertain to blood measurements, and can therefore affect blood vessels. Further, many of the complications of diabetes, including retinopathy, kidney disease and peripheral neuropathy, also have a vascular basis. In their review, Joyner and Green note that exercise is much more protective against cardiovascular disease than would be expected based on changes in traditional risk factors, including BMI, blood lipids and blood pressure [10]. They suggest a vicious cycle between autonomic dysfunction and endothelial dysfunction leading to cardiovascular disease, which can be prevented by exercise [10]. Here, the role of the endothe...

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