The Kidney as a Determinant of Genetic Hypertension

Rettig, Rainer; Grisk, Olaf

doi:10.1161/01.hyp.0000178189.68229.8a

Cited by 58 publications

(18 citation statements)

References 47 publications

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“…Nevertheless, it has been suggested that the kidney is the dominant mechanism for the long-term regulation of blood pressure; as such, an elevation in the renal perfusion pressure due to an increased arterial blood pressure enhances sodium and water excretion, leading to a decrease in body fluid volume and vice versa ("pressure natriuresis") (291). Moreover, renal transplantation studies further support the central role of the kidney in regulating blood pressure (725). The RAAS modulates renal function such that the activation of the RAAS causes a shift of the pressurenatriuresis curve to the right and the inhibition of the RAAS causes a shift to the left.…”

Section: A Blood Pressurementioning

confidence: 86%

Physiology of Kidney Renin

Castrop

Höcherl

Kurtz

et al. 2010

Physiological Reviews

232

277

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The protease renin is the key enzyme of the renin-angiotensin-aldosterone cascade, which is relevant under both physiological and pathophysiological settings. The kidney is the only organ capable of releasing enzymatically active renin. Although the characteristic juxtaglomerular position is the best known site of renin generation, renin-producing cells in the kidney can vary in number and localization. (Pro)renin gene transcription in these cells is controlled by a number of transcription factors, among which CREB is the best characterized. Pro-renin is stored in vesicles, activated to renin, and then released upon demand. The release of renin is under the control of the cAMP (stimulatory) and Ca2+(inhibitory) signaling pathways. Meanwhile, a great number of intrarenally generated or systemically acting factors have been identified that control the renin secretion directly at the level of renin-producing cells, by activating either of the signaling pathways mentioned above. The broad spectrum of biological actions of (pro)renin is mediated by receptors for (pro)renin, angiotensin II and angiotensin-( 1 – 7 ).

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Section: A Blood Pressurementioning

confidence: 86%

Physiology of Kidney Renin

Castrop

Höcherl

Kurtz

et al. 2010

Physiological Reviews

232

277

View full text Add to dashboard Cite

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“…Moreover, it has long been known that diuretic/natriuretic agents, such as hydrochlorothiazide, which directly counteract the tendency for salt and water retention, are effective antihypertensive agents in a large percentage of humans with essential hypertension (16,28,59). Also, renal transplant studies in humans and in animal models have demonstrated that "hypertension goes with the kidneys" (18,35,95).…”

Section: Salt Plasma Volume and The Kidneysmentioning

confidence: 99%

How does salt retention raise blood pressure?

Blaustein¹,

Zhang²,

Ling³

et al. 2006

American Journal of Physiology-Regulatory, Integrative and Comp

129

121

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A critical question in hypertension research is: How is long-term blood pressure controlled? Excessive NaCl ingestion or NaCl retention by the kidneys and the consequent tendency toward plasma volume expansion lead to hypertension. Nevertheless, the precise mechanisms linking salt to high blood pressure are unresolved. The discovery of endogenous ouabain, an adrenocortical hormone, provided an important clue. Ouabain, a selective Na ϩ pump inhibitor, has cardiotonic and vasotonic effects. Plasma endogenous ouabain levels are significantly elevated in Ϸ40% of patients with essential hypertension and in animals with several forms of salt-dependent hypertension. Also, prolonged ouabain administration induces hypertension in rodents. Mice with mutant Na ϩ pumps or Na/Ca exchangers (NCX) and studies with a ouabain antagonist and an NCX blocker are revealing the missing molecular mechanisms. These data demonstrate that ␣ 2 Na ϩ pumps and NCX1 participate in long-term regulation of vascular tone and blood pressure. Pharmacological agents or mutations in the ␣ 2 Na ϩ pump that interfere with the action of ouabain on the pump, and reduced NCX1 expression or agents that block NCX all impede the development of salt-dependent or ouabain-induced hypertension. Conversely, nanomolar ouabain, reduced ␣ 2 Na ϩ pump expression, and smooth muscle-specific overexpression of NCX1 all induce hypertension. Furthermore, ouabain and reduced ␣ 2 Na ϩ pump expression increase myogenic tone in isolated mesenteric small arteries in vitro, thereby tying these effects directly to the elevation of blood pressure. Thus, endogenous ouabain, and vascular ␣ 2 Na ϩ pumps and NCX1, are critical links between salt and hypertension. New pharmacological agents that act on these molecular links have potential in the clinical management of hypertension.ouabain; Na ϩ pump; Na/Ca exchanger; Ca 2ϩ ; myogenic tone HYPERTENSION, DEFINED AS A diastolic blood pressure (BP) Ն 90 mmHg and/or systolic BP Ն 140 mmHg, is endemic in Westernized societies. This is a very important public health issue because hypertension is a major risk factor for premature death and disability from heart attack, heart failure, stroke, and many other afflictions (16,59). In the United States, alone, Ϸ20% of the population (i.e., Ϸ50 million individuals) are hypertensive; moreover, more than half of all individuals over the age of 60 years have hypertension. In a small fraction of cases, the hypertension is due to specific causes, such as renal vascular disease or excessive secretion of aldosterone (primary aldosteronism) or catecholamines (pheochromocytoma). The vast majority (Ϸ90%) of patients, however, have elevated BP of unknown cause; hence the terms, primary or essential hypertension. The immediate cause for the elevated BP in nearly all chronic hypertensive persons is excessive narrowing of the small (resistance) arteries. Nevertheless, a key question in any discussion of hypertension is: What specific mechanisms actually lead to the abnormal arterial constriction and elevation ...

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“…Macroalbuminuria is a more severe form of albuminuria and may involve severe renal damage as the underlying cause [26]. The kidney has been shown to play a critical role in the pathogenesis of hypertension in the case of severe renal impairment [26][27][28], providing a possible pathway whereby macroalbuminuria may be highly associated with the odds of hypertension. Microalbuminuria and macroalbuminuria were more prevalent in non-Hispanic Blacks and Hispanics than in non-Hispanic Whites in the general US population in the present study (Figure 1).…”

Section: Discussionmentioning

confidence: 99%

Racial Disparity in the Associations of Microalbuminuria and Macroalbuminuria with Odds of Hypertension: Results from the NHANES Study in the United States

Liu

Tsilimingras

et al. 2013

ISRN Hypertension

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Background. Limited information is available on whether the associations of microalbuminuria and macroalbuminuria with the odds of hypertension differ among non-Hispanic Whites, non-Hispanic Blacks, and Hispanics. Methods. Cross-sectional data of 24,949 participants aged ≥18 years were collected from the National Health and Nutrition Examination Survey (NHANES) 1999-2008. Odds ratios of hypertension for microalbuminuria and macroalbuminuria were estimated by conducting weighted multiple logistic regression models. Results. After adjustment for extensive confounding factors, microalbuminuria is 1. 45 times in non-Hispanic Whites, non-Hispanic Blacks, and Hispanics, respectively. The odds of hypertension for microalbuminuria (versus normalbuminuria) were 52% higher in non-Hispanic Blacks and 98% higher in Hispanics than in non-Hispanic Whites; the odds of hypertension for macroalbuminuria (versus normalbuminuria) did not differ among racial groups. Conclusion. Racial differences in the relation between microalbuminuria and hypertension are prevalent among non-Hispanic Whites, non-Hispanic Blacks, and Hispanics. More screening efforts should be encouraged in normotensive non-Hispanic Blacks and Hispanics with microalbuminuria.

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The Kidney as a Determinant of Genetic Hypertension

Cited by 58 publications

References 47 publications

Physiology of Kidney Renin

Physiology of Kidney Renin

How does salt retention raise blood pressure?

Racial Disparity in the Associations of Microalbuminuria and Macroalbuminuria with Odds of Hypertension: Results from the NHANES Study in the United States

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