Increased Activation of Sympathetic Nervous System and Endothelin by Mental Stress in Normotensive Offspring of Hypertensive Parents

Noll, Georg; Wenzel, René R.; Schneider, Martin; Oesch, Valérie; Binggeli, Christian; Shaw, Sidney; Weidmann, P; Lüscher, Thomas F.

doi:10.1161/01.cir.93.5.866

Cited by 175 publications

(148 citation statements)

References 28 publications

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“…Consistent with prior studies in humans and rats,2, 11, 12, 13, 14, 15, 16, 20, 21 flox mice exhibited a significant increase in plasma ET‐1 in response to CSS, whereas VEETKO mice exhibited no change in plasma ET‐1 following CSS. We found that pulmonary ET receptor expression and affinity are similar in VEETKO and flox mice, suggesting no differences in ET‐1 clearance capacity in VEETKO and flox mice.…”

Section: Discussionsupporting

confidence: 88%

“…Multiple studies in humans have observed an increase in plasma ET‐1 in response to laboratory‐induced stress,11, 12, 13, 14, 15, 16 and these findings have been further validated by a large clinical study of male and female participants 2. More important, prior studies have highlighted the importance of both a family history of CVD and preexisting CVD as modifiers of the stress responsiveness of plasma ET‐1, as reviewed by Yammine et al 8.…”

Section: Perspectivesmentioning

confidence: 99%

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Acute Pressor Response to Psychosocial Stress Is Dependent on Endothelium‐Derived Endothelin‐1

Fox

Becker

Loria

et al. 2018

JAHA

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BackgroundAcute psychosocial stress provokes increases in circulating endothelin‐1 (ET‐1) levels in humans and animal models. However, key questions about the physiological function and cellular source of stress‐induced ET‐1 remain unanswered. We hypothesized that endothelium‐derived ET‐1 contributes to the acute pressor response to stress via activation of the endothelin A receptor.Methods and ResultsAdult male vascular endothelium‐specific ET‐1 knockout mice and control mice that were homozygous for the floxed allele were exposed to acute psychosocial stress in the form of cage switch stress (CSS), with blood pressure measured by telemetry. An acute pressor response was elicited by CSS in both genotypes; however, this response was significantly blunted in vascular endothelium‐specific ET‐1 knockout mice compared with control mice that were homozygous for the floxed allele. In mice pretreated for 3 days with the endothelin A antagonist, ABT‐627, or the dual endothelin A/B receptor antagonist, A‐182086, the pressor response to CSS was similar between genotypes. CSS significantly increased plasma ET‐1 levels in control mice that were homozygous for the floxed allele. CSS failed to elicit an increase in plasma ET‐1 in vascular endothelium‐specific ET‐1 knockout mice. Telemetry frequency domain analyses suggested similar autonomic responses to stress between genotypes, and isolated resistance arteries demonstrated similar sensitivity to α1‐adrenergic receptor‐mediated vasoconstriction.ConclusionsThese findings specify that acute stress‐induced activation of endothelium‐derived ET‐1 and subsequent endothelin A receptor activation is a novel mediator of the blood pressure response to acute psychosocial stress.

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Section: Discussionsupporting

confidence: 88%

Section: Perspectivesmentioning

confidence: 99%

Acute Pressor Response to Psychosocial Stress Is Dependent on Endothelium‐Derived Endothelin‐1

Fox

Becker

Loria

et al. 2018

JAHA

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“…40 Although the precise mechanism involved in this failure is not clearly understood, an increased activation of sympathetic nervous system may be a mechanism contributing to the exaggerated exercise BP, and may probably have a key role in the pathogenesis of essential hypertension. 13,41,42 Previous studies have shown that normotensive men offspring of hypertensive parents show increased sympathetic nervous system activity in response to mental stress, 13 hand grip exercise 41 and GXT. 42 This study demonstrates that young normotensive women offspring of hypertensive parents also have increased resting, exercise and recovery NE, and exercise and recovery EPI than women with normotensive parents.…”

Section: Pwvmentioning

confidence: 99%

“…Higher exercise BP during a GTX has been associated with decreased endothelial vasodilator function in hypertensive men and women, 43 and several studies have shown that the basal release of endothelium-derived vasodilator nitric oxide is impaired in hypertensive subjects 44 and its normotensive offsprings. 45 Moreover, the levels of endothelium-derived vasoconstrictor ET-1 has shown to be increased in normotensive male offsprings of hypertensive parents during mental stress 13 and hand grip exercise. 41 In this study, we demonstrated for the first time an increase in ET-1 and decrease in NOx (metabolities of nitric oxide), during the basal, exercise and recovery phases of a GXT, in young normotensive women offspring of hypertensive parents, suggesting that the exaggerated exercise BP present in these women may be in part a function of an impaired endothelial vasodilator function.…”

Section: Pwvmentioning

confidence: 99%

“…For example, increased arterial stiffness in nonhypertensive offspring of hypertensive subjects have been shown in some [8][9][10] but not all studies. 11,12 Also, increased sympathetic activity in response to mental 13 or physical 14 stress has been shown in normotensive offspring of hypertensive parents, but there are contradictory findings relating to resting sympathetic activity. 7,[15][16][17][18][19] There are some issues regarding the methodology of family history of hypertension investigations that may explain these contradictory results.…”

Section: Introductionmentioning

confidence: 99%

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Haemodynamic, metabolic and neuro-humoral abnormalities in young normotensive women at high familial risk for hypertension

Ciolac

Bocchi²,

Bortolotto³

et al. 2010

J Hum Hypertens

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We analysed the haemodynamic, metabolic and hormonal status at rest and in response to exercise, in young normotensive women with two hypertensive parents (FH þ þ ; n ¼ 17; 25.1±4.8 years), one hypertensive parent (FH þ ; n ¼ 18; 24.9 ± 4.1 years) and normotensive parents (FHÀ; n ¼ 15; 25.3 ± 3.8 years). Casual and ambulatorial blood pressure (BP), carotid-femoral pulse wave velocity (PWV) and biochemistry were analysed. BP, nor-epinephrine (NE), epinephrine (EPI), endothelin-1 (ET-1) and nitrite/nitrate (NOx) levels were also analysed during a graded exercise test (GXT). Casual and ambulatorial BP were not different between groups, but PWV was 7.5 and 12.6% higher in FH þ þ than FH þ and FHÀ, respectively, and 4.8% higher in FH þ than FHÀ (Pp0.01). Insulin and insulin-to-glucose ratio were increased in FH þ þ and FH þ (Po0.05), and lowdensity lipoprotein (LDL)-cholesterol tended to be higher only in FH þ þ (P ¼ 0.07). FH þ þ showed higher exercise and recovery diastolic BP and EPI levels, and increased resting, exercise and recovery NE, and ET-1 levels than FHÀ (Po0.05). FH þ showed only greater resting, exercise and recovery NE, and rest ET-1 (Po0.05). Resting, exercise and recovery NOx were lower in FH þ þ and FH þ than FHÀ (Po0.01). Haemodynamic, metabolic and hormonal abnormalities were presented in nonhypertensive young women offspring of hypertensive parents before any increase in BP. Greater abnormalities were observed in women with a strong family history of hypertension (FH þ þ ). These results suggest that there is an early vascular, metabolic and hormonal involvement in a familial hypertensive disorder.

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Hypertension: Time‐Frequency Analysis for Early Diagnosis

Davrath

Pinhas

Toledo

et al. 2006

Wiley Encyclopedia of Biomedical Engineering

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Hypertension is the most common disease in industrialized nations, and it markedly increases both morbidity and mortality from cardiovascular and many other diseases. Yet, appropriate interventions can delay and possibly prevent the development of hypertension and ensuing complications. The risk of cardiovascular death doubles in a near linear fashion for each 20/10 mm Hg increment in blood pressure levels above 115/75 mm Hg. Despite this, no techniques are currently available to identify individuals at increased risk for developing hypertension. Autonomic dysfunction has been quantified at progressive stages of hypertension, providing insight into the malfunctions characteristic of pre‐hypertension, mild, and full‐blown hypertension. Newly developed time‐frequency analysis tools provide a promising prospect for simple, noninvasive identification of individuals with a “pre‐hypertensive” profile. Early identification of individuals prone to developing hypertension may allow for aggressive early intervention to slow down, or even halt, disease progression.

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Increased Activation of Sympathetic Nervous System and Endothelin by Mental Stress in Normotensive Offspring of Hypertensive Parents

Cited by 175 publications

References 28 publications

Acute Pressor Response to Psychosocial Stress Is Dependent on Endothelium‐Derived Endothelin‐1

Acute Pressor Response to Psychosocial Stress Is Dependent on Endothelium‐Derived Endothelin‐1

Haemodynamic, metabolic and neuro-humoral abnormalities in young normotensive women at high familial risk for hypertension

Hypertension: Time‐Frequency Analysis for Early Diagnosis

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