Abnormalities of glucocorticoid metabolism and the renin???angiotensin system: a four-corners approach to the identification of genetic determinants of blood pressure

Watt, Graham; Harrap, Stephen B; Foy, Christopher; Holton, David; Edwards, Hugh V.; Davidson, H. Rosemarie; Connor, J. M.; Lever, A. F.; Fraser, Robert

doi:10.1097/00004872-199205000-00011

Cited by 290 publications

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“…There is growing evidence that both stress and glucocorticoids contribute to the etiology of cardiovascular disease; however, the role of glucocorticoids in the stress response has long been a matter of debate (1,3,5,13,15,28,30,31,35,36,38,39,42,48,49,52,58,61,65,67,68,70,71). Recent research has led to the general hypothesis that stress-induced increases in glucocorticoids act in the brain to prepare the organism for future events (12,52).…”

Section: Perspectivesmentioning

confidence: 99%

“…Acute stress rapidly increases blood pressure, heart rate, plasma glucocorticoid concentration, and blood glucose levels (8), while chronic or repeated stress is associated with increases in baseline blood pressure and glucocorticoids (17). Chronically elevated glucocorticoids increase morbidity and mortality from cardiovascular disease and alterations in the glucocorticoid receptor (GR), and in glucocorticoid metabolizing enzymes are associated with hypertension and cardiovascular disease in humans (28,30,35,36,39,48,49,61,65,67,70,71). Thus, chronic stress-induced elevations in glucocorticoids likely contribute to the adverse effects of stress on cardiovascular health.…”

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confidence: 99%

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Chronic blockade of hindbrain glucocorticoid receptors reduces blood pressure responses to novel stress and attenuates adaptation to repeated stress

Bechtold

Patel²,

Hochhaus³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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Exogenous glucocorticoids act within the hindbrain to enhance the arterial pressure response to acute novel stress. Here we tested the hypothesis that endogenous glucocorticoids act at hindbrain glucocorticoid receptors (GR) to augment cardiovascular responses to restraint stress in a model of stress hyperreactivity, the borderline hypertensive rat (BHR). A 3-to 4-mg pellet of the GR antagonist mifepristone (Mif) was implanted over the dorsal hindbrain (DHB) in WistarKyoto (WKY) and BHRs. Control pellets consisted of either sham DHB or subcutaneous Mif pellets. Rats were either subjected to repeated restraint stress (chronic stress) or only handled (acute stress) for 3-4 wk, then all rats were stressed on the final day of the experiment. BHR showed limited adaptation of the arterial pressure response to restraint, and DHB Mif significantly (P Յ 0.05) attenuated the arterial pressure response to restraint in both acutely and chronically stressed BHR. In contrast, WKY exhibited a substantial adaptation of the pressure response to repeated restraint that was significantly reversed by DHB Mif. DHB Mif and chronic stress each significantly increased baseline plasma corticosterone concentration and adrenal weight and reduced the corticosterone response to stress in all rats. We conclude that endogenous corticosterone acts via hindbrain GR to enhance the arterial pressure response to stress in BHR, but to promote the adaptation of the arterial pressure response to stress in normotensive rats. Endogenous corticosterone also acts in the hindbrain to restrain corticosterone at rest but to maintain the corticosterone response to stress in both BHR and WKY rats. corticosterone; brain; nucleus of the solitary tract; hypothalamicpituitary-adrenal axis; chronic stress EXAGGERATED CARDIOVASCULAR responses to acute stress and chronic stress increase the risk for hypertension and cardiovascular disease (1,3,13,15,31,38,42,58,68). Acute stress rapidly increases blood pressure, heart rate, plasma glucocorticoid concentration, and blood glucose levels (8), while chronic or repeated stress is associated with increases in baseline blood pressure and glucocorticoids (17). Chronically elevated glucocorticoids increase morbidity and mortality from cardiovascular disease and alterations in the glucocorticoid receptor (GR), and in glucocorticoid metabolizing enzymes are associated with hypertension and cardiovascular disease in humans (28,30,35,36,39,48,49,61, 65,67,70,71). Thus, chronic stress-induced elevations in glucocorticoids likely contribute to the adverse effects of stress on cardiovascular health.The mechanisms by which glucocorticoids modulate cardiovascular stress responses are not fully understood. A review by Sapolsky et al. (52) concluded that glucocorticoids act permissively to enhance the arterial pressure response to many physical stressors, in part by supporting the peripheral effects of catecholamines. Other studies indicate that chronic, systemic elevations in glucocorticoids enhance cardiovascular and catecholamine re...

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Section: Perspectivesmentioning

confidence: 99%

mentioning

confidence: 99%

Chronic blockade of hindbrain glucocorticoid receptors reduces blood pressure responses to novel stress and attenuates adaptation to repeated stress

Bechtold

Patel²,

Hochhaus³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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“…For example, young offspring of hypertensive parents themselves have a significant predisposition to hypertension. 1 A number of candidate genes present themselves. Those that influence renal sodium handling, including components of the cytoskeleton, 2 the renin-angiotensin system (RAS), 3 and factors that affect the regulation of secretion and action of aldosterone 4 are obvious candidates.…”

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confidence: 99%

α-Adducin and Angiotensin I–Converting Enzyme Polymorphisms in Essential Hypertension

et al. 2000

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Abstract-This study focused on two genes that have previously been implicated in hypertension and may influence renal sodium handling, adducin, and angiotensin I-converting enzyme (ACE). We compared their polymorphic frequencies and interaction in patients with essential hypertension (nϭ128) and individually age-and gender-matched normotensive control subjects. The ␣-adducin G460W polymorphism was genotyped by DNA amplification and restriction digestion.The ACE I/D polymorphism was assayed by a triple-primer method, with a "nested" polymerase chain reaction primer situated completely within the insertion sequence of the I allele. The distributions of genotypes and alleles for the two polymorphisms were not significantly different between the case and control populations, and the cross-classification of cases by ␣-adducin and ACE genotype gave a distribution similar to that of control subjects. We have previously reported that the distributions of genotypes for two linked polymorphisms in the aldosterone synthase gene (one in the steroidogenic factor-1

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“…Therefore, an increase in the circulating AGT level can increase blood Ang II levels. The ability of AGT to produce corresponding level of Ang II links AGT to hypertension [44][45][46]. Published reports also indicate direct relation between AGT and blood pressure.…”

Section: Pathophysiologymentioning

confidence: 99%

“…Published reports also indicate direct relation between AGT and blood pressure. For instance, a highly significant relationship between plasma concentration of AGT and blood pressure in human subjects [44], higher plasma AGT levels in hypertensive subjects and in offspring of hypertensive parents compared against normotensives [44,46], expression of AGT gene in multiple tissues and organs are directly involved in blood pressure regulation [47], Moreover, increase in blood pressure is observed in transgenic animals that over-express AGT gene [45,48,49], while, lowering of blood pressure in AGT gene knockout mice has also been observed [45]. Increasing copy number of AGT up to four copies in mice, causes successive increases in blood pressure [48].…”

Section: Pathophysiologymentioning

confidence: 99%

Role of Angiotensin Peptides Precursor in Ethanol Mediated Hepato toxicity: Perspective on Angiotensinogen

Ansari¹

2012

TOGASJ

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Alcohol usage poses serious social and economical challenges. Its overuse is responsible for loss of billions of dollars due to fatal accidents and causes multiple diseases. Chronic alcoholism leads to liver disorders, including steatosis, hepatitis, fibrosis and cirrhosis. Both binge and chronic alcohol drinking result in blood pressure elevation and hypertension. As a significant mechanism, changes in the levels of angiotensinogen-released peptides play an important role in advanced alcohol liver disease. This review summarizes some of the studies that have demonstrated their role in liver fibrosis, cirrhosis and hypertension. Further, the individual variants and polymorphic sites may play a role in alcoholmediated regulation of angiotensinogen. Possible role of human angiotensinogen on alcohol hepatotoxicity is also discussed.

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Abnormalities of glucocorticoid metabolism and the renin???angiotensin system: a four-corners approach to the identification of genetic determinants of blood pressure

Cited by 290 publications

References 0 publications

Chronic blockade of hindbrain glucocorticoid receptors reduces blood pressure responses to novel stress and attenuates adaptation to repeated stress

Chronic blockade of hindbrain glucocorticoid receptors reduces blood pressure responses to novel stress and attenuates adaptation to repeated stress

α-Adducin and Angiotensin I–Converting Enzyme Polymorphisms in Essential Hypertension

Role of Angiotensin Peptides Precursor in Ethanol Mediated Hepato toxicity: Perspective on Angiotensinogen

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