Although the etiology of essential hypertension remains unknown, it is clear that multiple factors may contribute to the pathogenesis of hypertension. Hypertension is an outcome of the interaction of multiple genetic and environmental factors. Several epidemiological studies indicated that the incidence of arterial stiffness and hypertension and related cardiovascular disease (stroke, myocardial infarction) is higher in the aged than in the young population.1–4 The prevalence of arterial stiffening and hypertension increases with age.1,5 Based on an epidemiological study,6 the prevalence of hypertension is more than doubled in the elderly than in the young population. More than two-thirds of individuals after 65 years of age experience hypertension according to the Seventh Report of the Joint National Committee (JNC-7).7 Therefore, it is generally thought that hypertension is an aging disorder. In recent years, metabolic syndrome and hypertension are increasingly seen in the middle-aged and young populations. In these subpopulations, insulin resistance and overproduction of adipokines impair endothelial and heart function leading to early and accelerated cardiovascular aging. It was reported that premature aging (progeria) is associated with accelerated vascular stiffening or vascular aging.8

Aging is defined as the age-related decline in physiological function essential for survival and fertility. Cardiovascular aging is an important factor that determines life span. The wall of large conduit arteries, especially aorta, thicken and lose elasticity over time, and this process results in an increase in pulse wave velocity, an important and reliable measure of arterial stiffness. The increased arterial stiffness, whatever its underlying causes, would reduce the reservoir/buffering function of the conduit arteries near the heart and increase pulse wave velocity, both of which increase systolic and pulse pressure. Therefore, aging-related hypertension is characterized by a significant increase in systolic blood pressure with no change or even a …

Aging, arterial stiffness, and hypertension.

The double burden of malnutrition: aetiological pathways and consequences for health.

Epidemiological studies linking low birth weight and subsequent cardiometabolic disease have given rise to the hypothesis that events in fetal life permanently program subsequent cardiovascular risk. The effects of fetal programming may not be limited to the first-generation offspring. We have explored intergenerational effects in the dexamethasone-programmed rat, a model in which fetal exposure to excess glucocorticoid results in low birth weight with subsequent adult hyperinsulinemia and hyperglycemia underpinned by increased activity of the key hepatic gluconeogenic enzyme, phosphoenolpyruvate carboxykinase (PEPCK). We found that the male offspring of female rats that had been exposed prenatally to dexamethasone, but were not manipulated in their own pregnancy, also had reduced birth weight (5.66 ± 0.06 vs. 6.12 ± 0.06 g, P < 0.001), glucose intolerance, and elevated hepatic PEPCK activity (5.7 ± 0.6 vs. 3.3 ± 0.2 nmol.min -1 .mg protein -1 , P < 0.001). These effects resolved in a third generation. Similar intergenerational programming was observed in offspring of male rats exposed prenatally to dexamethasone mated with control females. The persistence of such programming effects through several generations, transmitted by either maternal or paternal lines, indicates the potential importance of epigenetic factors in the intergenerational inheritance of the programming phenotype and provides a basis for the inherited association between low birth weight and cardiovascular risk factors.

Intergenerational consequences of fetal programming by in utero exposure to glucocorticoids in rats : Fetal physiological programming

Many natural products present in our diet, including flavonoids, can prevent the progression of cancer and other diseases. Resveratrol, a natural polyphenol present in various fruits and vegetables, plays an important role as a therapeutic and chemopreventive agent used in the treatment of various illnesses. It exhibits effects against different types of cancer through different pathways. It additionally exerts antidiabetic, anti-inflammatory, and anti-oxidant effects in a variety of cell types. Furthermore, the cardiovascular protective capacities of resveratrol are associated with multiple molecular targets and may lead to the development of novel therapeutic strategies for atherosclerosis, ischemia/reperfusion, metabolic syndrome, and heart failure. Accordingly, this article presents an overview of recent developments in the use of resveratrol for the prevention and treatment of different diseases along with various mechanisms. In addition, the present review summarizes the most recent literature pertaining to resveratrol as a chemotherapeutic agent against multiple diseases and provides an assessment of the potential of this natural compound as a complementary or alternative medicine.

A comprehensive review of the health perspectives of resveratrol

Hypertension in women

Low birth weight serves as a crude proxy for impaired growth during fetal life and indicates a failure for the fetus to achieve its full growth potential. Low birth weight can occur in response to numerous etiologies that include complications during pregnancy, poor prenatal care, parental smoking, maternal alcohol consumption, or stress. Numerous epidemiological and experimental studies demonstrate that birth weight is inversely associated with blood pressure and coronary heart disease. Sex and age impact the developmental programming of hypertension. In addition, impaired growth during fetal life also programs enhanced vulnerability to a secondary insult. Macrosomia, which occurs in response to maternal obesity, diabetes, and excessive weight gain during gestation, is also associated with increased cardiovascular risk. Yet, the exact mechanisms that permanently change the structure, physiology, and endocrine health of an individual across their lifespan following altered growth during fetal life are not entirely clear. Transmission of increased risk from one generation to the next in the absence of an additional prenatal insult indicates an important role for epigenetic processes. Experimental studies also indicate that the sympathetic nervous system, the renin angiotensin system, increased production of oxidative stress, and increased endothelin play an important role in the developmental programming of blood pressure in later life. Thus, this review will highlight how adverse influences during fetal life and early development program an increased risk for cardiovascular disease including high blood pressure and provide an overview of the underlying mechanisms that contribute to the fetal origins of cardiovascular pathology.

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Fetal programming and cardiovascular pathology.

Hypertension is a risk factor for cardiovascular disease, the leading cause of death worldwide. Although multiple factors contribute to the pathogenesis of hypertension, studies by Dr David Barker reporting an inverse relationship between birth weight and blood pressure led to the hypothesis that slow growth during fetal life increased blood pressure and the risk for cardiovascular disease in later life. It is now recognized that growth during infancy and childhood, in addition to exposure to adverse influences during fetal life, contributes to the developmental programming of increased cardiovascular risk. Numerous epidemiological studies support the link between influences during early life and later cardiovascular health; experimental models provide proof of principle and indicate that numerous mechanisms contribute to the developmental origins of chronic disease. Sex has an impact on the severity of cardiovascular risk in experimental models of developmental insult. Yet, few studies examine the influence of sex on blood pressure and cardiovascular health in low-birth weight men and women. Fewer still assess the impact of ageing on sex differences in programmed cardiovascular risk. Thus, the aim of the present review is to highlight current data about sex differences in the developmental programming of blood pressure and cardiovascular disease.

Gender differences in developmental programming of cardiovascular diseases

Perinatal insults program sex differences in blood pressure, with males more susceptible than females. Aging may augment developmental programming of chronic disease, but the mechanisms involved are not clear. We previously reported that female growth-restricted offspring are normotensive after puberty. Therefore, we tested the hypothesis that age increases susceptibility to hypertension in female growth-restricted offspring. Blood pressure remained similar at 6 months of age; however, blood pressure was significantly elevated in female growth-restricted offspring relative to control by 12 months of age (137±3 vs 117±4 mm Hg; P P P P

Renal Denervation Abolishes the Age-Dependent Increase in Blood Pressure in Female Intrauterine Growth-Restricted Rats at 12 Months of Age

The Developmental Origins of Health and Disease (DOHaD) proposes that adverse events during early life program an increased risk for cardiovascular disease. Experimental models provide proof of concept but also indicate that insults during early life program sex differences in adult blood pressure and cardiovascular risk. This review will highlight the potential mechanisms that contribute to the etiology of sex differences in the developmental programming of cardiovascular disease.

https://www.physiology.org/doi/pdf/10.1152/physiol.00045.2013

Sex Differences in the Developmental Origins of Cardiovascular Disease

Placental insufficiency results in intrauterine growth restriction (IUGR) and hypertension in adult male growth-restricted rats. Although renal ANG II and plasma renin activity do not differ between growth-restricted and control rats, blockade of the renin-angiotensin system (RAS) abolishes hypertension in growth-restricted rats, suggesting that the RAS contributes to IUGR-induced hypertension. Moreover, castration abolishes hypertension in growth-restricted rats, indicating an important role for testosterone. Therefore, we hypothesized that enhanced responsiveness to ANG II contributes to hypertension in this model of IUGR and that androgens may play a pivotal role in this enhanced response. Physiological parameters were determined at 16 wk of age in male rats pretreated with enalapril (40 mg·kg−1·day−1) for 1 wk. Baseline blood pressures were similar between growth-restricted (112 ± 3 mmHg) and control (110 ± 2 mmHg) rats; however, an enhanced pressor response to acute ANG II (100 ng·kg−1·min−1 for 30 min) was observed in growth-restricted (160 ± 2 mmHg) vs. control (136 ± 2 mmHg; P < 0.05) rats. Castration abolished the enhanced pressor response to acute ANG II in growth-restricted (130 ± 2 mmHg) rats with no significant effect on blood pressure in controls (130 ± 2 mmHg). Blood pressure was increased to a similar extent above baseline in response to acute phenylephrine (100 μg/min) in control (184 ± 5 mmHg) and growth-restricted (184 ± 8 mmHg) rats, suggesting the enhanced pressor response in growth-restricted rats is ANG II specific. Thus, these results suggest that growth-restricted rats exhibit an enhanced responsiveness to ANG II that is testosterone dependent and indicate that the RAS may serve as an underlying mechanism in mediating hypertension programmed in response to IUGR.

John Henry Dasinger

Papers

Fetal programming and cardiovascular pathology.

Gender differences in developmental programming of cardiovascular diseases

Renal Denervation Abolishes the Age-Dependent Increase in Blood Pressure in Female Intrauterine Growth-Restricted Rats at 12 Months of Age

Sex Differences in the Developmental Origins of Cardiovascular Disease

Enhanced sensitivity to acute angiotensin II is testosterone dependent in adult male growth-restricted offspring.