The Role of Renin in the Exaggerated Natriuresis of Hypertension

Krakoff, Lawrence R.; Goodwin, F. J.; Baer, Leslie; Tomues, Manuel; Laragh, John H.

doi:10.1161/01.cir.42.2.335

Cited by 69 publications

(22 citation statements)

References 32 publications

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“…In contrast, our experiments demonstrated an enhanced ability to excrete an acute salt load in LSD1-deficient mice. This result is consistent with previous studies in humans, where low renin hypertensives hyperexcreted a salt load in contrast to normotensives or non-modulating hypertensives (a normal renin form of salt-sensitive hypertension) (Cottier et al 1958;Krakoff et al 1970;Luft et al 1977;Rydstedt et al 1986;Hollenberg et al 1986). In this study (data not shown) and previously (Pojoga et al 2011b), renin and aldosterone levels were suppressed in LSD1-deficient mice on HS diet, indicating that activation of the RAS is not a driving force for elevated blood pressure.…”

Section: Animal Studiessupporting

confidence: 93%

Lysine-specific demethylase-1 modifies the age effect on blood pressure sensitivity to dietary salt intake

Krug

Tille

Sun

et al. 2012

AGE

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How interactions of an individual's genetic background and environmental factors, such as dietary salt intake, result in age-associated blood pressure elevation is largely unknown. Lysine-specific demethylase-1 (LSD1) is a histone demethylase that mediates epigenetic regulation and modification of gene transcription. We have shown previously that hypertensive African-American minor allele carriers of the LSD1 single nucleotide polymorphism (rs587168) display blood pressure salt sensitivity. Our goal was to further examine the effects of LSD1 genotype variants on interactions between dietary salt intake, age, and blood pressure. We found that LSD1 single nucleotide polymorphism (rs7548692) predisposes to increasing salt sensitivity during aging in normotensive Caucasian subjects. Using a LSD1 heterozygous knockout mouse model, we compared blood pressure values on low (0.02 % Na + ) vs. high (1.6 % Na + ) salt intake. Our results demonstrate significantly increased blood pressure salt sensitivity in LSD1-deficient compared to wild-type animals with age, confirming our findings of salt sensitivity in humans. Elevated blood pressure in LSD1 +/− mice is associated with total plasma volume expansion and altered renal Na + excretion. In summary, our human and animal studies demonstrate that LSD1 is a genetic factor that interacts with dietary salt intake modifying age-associated blood pressure increases and salt sensitivity through alteration of renal Na + handling.

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Section: Animal Studiessupporting

confidence: 93%

Lysine-specific demethylase-1 modifies the age effect on blood pressure sensitivity to dietary salt intake

Krug

Tille

Sun

et al. 2012

AGE

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“…4 To characterize renal function in a setting of chronic hypertension, various animal models have been used. Recent investigations have focused on genetically hypertensive rats to study the mechanisms involved in the pathogenesis and maintenance of essential hypertension.…”

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confidence: 99%

Renal function of conscious spontaneously hypertensive rats.

Beierwaltes¹,

Arendshorst²

1978

Circulation Research

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SUMMARY Renal clearance studies were performed in conscious 13-week-old spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) before and during volume expansion by intravenous infusion of isotonic saline. Mean arterial pressure and filtration fraction were greater in SHR, whereas fractional and absolute excretion of sodium and water, glomerular filtration rate, and renal plasma flow in SHR and WKY were not statistically different. This was the case during hydropenia and volume expansion. We did not observe an exaggerated natriuresis after intravenous loading when unanesthetized SHR were compared with the response of WKY. These observations suggest that the kidneys of genetically hypertensive rats of the Okamoto-Aoki strain have adapted to an elevated renal perfusion pressure or that hypertension is required to normalize renal function so that excretion is appropriately matched with intake. IN 1946, FARNSWORTH 1 reported that patients with essential hypertension excrete salt and water more rapidly than normotensive subjects after acute volume expansion. Although this observation has been documented repeatedly, 2 "5 the renal mechanism(s) responsible for this "exaggerated" natriuretic response is poorly understood. Enhanced sodium excretion has been observed after intravenous administration of hyper-, iso-, or hypotonic saline and is not associated with consistent changes in glomerular filtration rate, renal plasma flow, or plasma sodium concentration.2 -3 On the other hand, not all patients with essential hypertension respond to acute volume expansion with enhanced salt and water excretion. 4 To characterize renal function in a setting of chronic hypertension, various animal models have been used. Recent investigations have focused on genetically hypertensive rats to study the mechanisms involved in the pathogenesis and maintenance of essential hypertension. Genetically or spontaneously hypertensive rats (SHR) are selectively inbred, developing high blood pressure as a function of age, and offer the attractive feature that an experimental maneuver is not required to induce hypertension in a previously normotensive animal. Reports of renal function in SHR on the Okamoto-Aoki strain" have been conflicting with regard to the kidneys' ability to excrete an acute saline load. Following intravenous administration of a salt load, sodium excretion of anesthetized SHR has been found to be less than, 7 sodium faster than normotensive Wistar-Kyoto rats (WKY) in response to an intragastric load of saline. In contrast, we have observed recently" that anesthetized 13-week-old SHR did not excrete sodium and water more rapidly than WKY when acute volume expansion was induced by intravenous infusion of saline. The present study employed clearance methodology to evaluate renal function of conscious SHR and WKY at 13 weeks of age during hydropenic conditions and following intravenous infusion of a moderate saline load. Although SHR had a significantly higher mean arterial pressure than WKY, fractional and ...

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“…In normal man, volume expansion after sodium loading has been demonstrated to suppress the secretion of renin and aldosterone (1)(2)(3)(4)(5). A recent study, demonstrating a rapid suppression of blood levels of renin, angiotensin, and aldosterone after infusions of small volumes of saline, suggested a specific role for the sodium ion in the regulation of the renin-aldosterone axis (5).…”

Section: Introductionmentioning

confidence: 99%