Pathogenesis and Clinical Physiology of Hypertension

Singh, Mukesh; Mensah, George A.; Bakris, George L.

doi:10.1016/j.ccl.2010.07.001

Cited by 85 publications

(55 citation statements)

References 85 publications

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“…4 The spontaneously hypertensive rat (SHR) is a model of essential hypertension in which blood pressure (BP) begins to rise after 6 weeks of age, ultimately reaching stable pressures of ≈180 to 200 mm Hg. Recently, Komolova et al reported evidence of altered vascular resistance profiles and renal hemodynamics as early as 3 weeks of age in the SHR, 5 implicating these early functional changes as a cause, rather than a consequence, of hypertension in this model.…”

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confidence: 99%

Perinatal Resveratrol Supplementation to Spontaneously Hypertensive Rat Dams Mitigates the Development of Hypertension in Adult Offspring

et al. 2016

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ypertension is an important and modifiable risk factor for cardiovascular disease, affecting ≈1 in 4 adults worldwide. 1 In the United States, hypertension is estimated to account for >$46 billion annually in healthcare services, medication, and lost productivity, 2 and these costs are expected to increase substantially over the coming decades. A universal consensus is that prevention, rather than treatment, is a more strategic and cost-effective approach to reducing the burden of cardiovascular disease in coming decades.Essential hypertension, in which known primary causes (eg, renovascular disease, pheochromocytoma, monogenic causes, etc) are not present, makes up 95% of hypertension worldwide.3 Although the pathogenesis of essential hypertension is multifactorial and complex, subclinical changes in vascular function often precede the development of hypertension and circulatory decline. 4 The spontaneously hypertensive rat (SHR) is a model of essential hypertension in which blood pressure (BP) begins to rise after 6 weeks of age, ultimately reaching stable pressures of ≈180 to 200 mm Hg. Recently, Komolova et al reported evidence of altered vascular resistance profiles and renal hemodynamics as early as 3 weeks of age in the SHR, 5 implicating these early functional changes as a cause, rather than a consequence, of hypertension in this model. As such, the developmental period before weaning (ie, See Editorial Commentary, pp 829-830Abstract-This study was undertaken to determine whether perinatal maternal resveratrol (Resv)-a phytoalexin known to confer cardiovascular protection-could prevent the development of hypertension and improve vascular function in adult spontaneously hypertensive rat offspring. Dams were fed either a control or Resv-supplemented diet (4 g/kg diet) from gestational day 0.5 until postnatal day 21. Indwelling catheters were used to assess blood pressure and vascular function in vivo; wire myography was used to assess vascular reactivity ex vivo. Perinatal Resv supplementation in dams had no effect on fetal body weights, albeit continued maternal treatment postnatally resulted in growth restriction in offspring by postnatal day 21; growth restriction was no longer evident after 5 weeks of age. Maternal perinatal Resv supplementation prevented the onset of hypertension in adult offspring (−18 mm Hg; P=0.007), and nitric oxide synthase inhibition (with l-NG-nitroarginine methyl ester) normalized these blood pressure differences, suggesting improved nitric oxide bioavailability underlies the hemodynamic alterations in the Resv-treated offspring. In vivo and ex vivo, vascular responses to methylcholine were not different between treatment groups, but prior treatment with l-NG-nitroarginine methyl ester attenuated the vasodilation in untreated, but not Resv-treated adult offspring, suggesting a shift toward nitric oxide-independent vascular control mechanisms in the treated group. Finally, bioconversion of the inactive precursor big endothelin-1 to active endothelin-1 in isolated mesenteric art...

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Perinatal Resveratrol Supplementation to Spontaneously Hypertensive Rat Dams Mitigates the Development of Hypertension in Adult Offspring

et al. 2016

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“…Endothelial dysfunction is frequently regarded as a reduced bioavailability or function of EDNO, blunted EDHF responses and hypersensitivity to vasoconstrictors. 49 In SHR, specifically EDCFs are described as a manifestation of endothelial dysfunction and these EDCFmediated contractions in response to stimulation of the artery with ACh are fully inhibited by a cyclo-oxygenase inhibitor (INDO). In 32-weekold SHR investigated in this study, a moderate EDCF component was observed.…”

Section: Discussionmentioning

confidence: 99%

Dual NEP/ECE inhibition improves endothelial function in mesenteric resistance arteries of 32-week-old SHR

et al. 2017

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Endothelin 1 (ET-1), a potent vasoconstrictor, pro-mitogenic and pro-inflammatory peptide, may promote development of endothelial dysfunction and arterial remodeling. ET-1 can be formed through cleavage of big-ET-1 by endothelin-converting enzyme (ECE) or neutral endopeptidase (NEP). We investigated whether chronic treatment with the novel dual NEP/ECE inhibitor SOL1 improves functional and structural properties of resistance-sized arteries of 32-week-old male spontaneously hypertensive rats (SHR). SHR received a chronic 4-week treatment with SOL1, losartan or hydralazine. We then compared effects of inhibition of NO synthase (NOS) (100 μM L-NAME), blockade of ET A -and ET B -receptors (10 μM bosentan) and stimulation of the endothelium with 0.001-10 μM acetylcholine (ACh) in isolated third-order mesenteric resistance arteries. Losartan and hydralazine significantly lowered blood pressure. Losartan decreased the media-to-lumen ratio of resistance arteries. L-NAME (1) increased arterial contractile responses to K + (5.9-40 mM) in the losartan, SOL1 and vehicle group and (2) increased the sensitivity to phenylephrine (PHE; 0.16-20 μM) in the SOL1 group but not in the losartan, hydralazine and vehicle group. Relaxing responses to ACh in the absence or presence of L-NAME during contractions induced by either 10 μM PHE or 40 mM K + were not altered by any in vivo treatment. Acute treatment with bosentan did, however, significantly improve maximal relaxing responses involving endothelium-derived nitric oxide and -hyperpolarizing factors in the SOL1 group but not in the losartan, hydralazine or vehicle group. Thus, chronic inhibition of NEP/ECE improved basal endothelial function but did not alter blood pressure, resistance artery structure and stimulated endothelium-dependent relaxing responses in 32-week-old SHR.

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“…For example, the increase of blood flow in the legs in response to methacholine, a measure of endothelium-dependent vasorelaxation, is reduced in non diabetic insulin-resistant individuals (Steinberg et al, 1996); moreover, nitric oxide-dependent flow-mediated dilatation of the brachial artery is impaired in hypertensive (Higashi et al, 1997) and normotensive (Balletshofer et al, 2000) subjects with insulin resistance. It is well established that a decreased bioavailability of nitric oxide contributes to endothelial dysfunction (Singh et al, 2010); furthermore, nitric oxide may modulate insulin sensitivity (Pitocco et al, 2010). Activation of nitric oxide synthase augments blood flow to insulin-sensitive tissues, such as skeletal muscle, liver, and adipose tissue, and its activity is impaired in insulin resistance; whereas inhibition of nitric oxide synthase reduces the microvascular delivery of nutrients and blunts insulinstimulated glucose uptake in skeletal muscle (Shi & Vanhoutte, 2009;Roberts & Sindhu, 2009).…”

Section: High Blood Pressure and Type 2 Diabetesmentioning

confidence: 99%

Antihypertensive Treatment in Type 2 Diabetic Patients

Carella¹

2011

Recent Advances in the Pathogenesis, Prevention and Management of Type 2 Diabetes and Its Complications

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Pathogenesis and Clinical Physiology of Hypertension

Cited by 85 publications

References 85 publications

Perinatal Resveratrol Supplementation to Spontaneously Hypertensive Rat Dams Mitigates the Development of Hypertension in Adult Offspring

Perinatal Resveratrol Supplementation to Spontaneously Hypertensive Rat Dams Mitigates the Development of Hypertension in Adult Offspring

Dual NEP/ECE inhibition improves endothelial function in mesenteric resistance arteries of 32-week-old SHR

Antihypertensive Treatment in Type 2 Diabetic Patients

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