Abnormal Renal Sodium Handling in Essential Hypertension. Relation to Failure of Renal and Adrenal Modulation of Responses to Angiotensin II

Nk, Hollenberg; Moore, Thomas J.; Shoback, Dolores; Redgrave, Jamie; Rabinowe, Steven L.; Williams, Gordon H.

doi:10.1016/s0022-5347(17)44032-8

Cited by 41 publications

(65 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…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

View full text Add to dashboard Cite

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.

show abstract

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

View full text Add to dashboard Cite

show abstract

“…43 The 7-day diet period was chosen based on prior evidence demonstrating an average time to sodium homeostasis of approximately 5 days in hypertensive patients. 26 Thus, the longer duration and higher sodium intake would actually reduce the frequency of false positives due to delayed suppression of urine aldosterone excretion, which might have appeared with a shorter period and/or lesser sodium intake.…”

Section: Discussionmentioning

confidence: 99%

“…The duration of each diet period was chosen based on prior evidence demonstrating an average time to sodium homeostasis of approximately 5 days in hypertensive patients. 26 High-sodium diet was accomplished by continuing the individual's usual diet supplemented with 2-3 packets of bullion broth at lunch and dinner (adding approximately 100-150 mmol Na/day). The Dietary Core of each center's General Clinical Research Center (GCRC) prepared all low-sodium meals, drinks and snacks after an intake interview with each participant to estimate usual caloric intake.…”

Section: Study Participant Selectionmentioning

confidence: 99%

Prevalence of primary hyperaldosteronism in mild to moderate hypertension without hypokalaemia

et al. 2005

View full text Add to dashboard Cite

Screening for primary hyperaldosteronism (PHA) is often indicated in individuals with resistant hypertension or hypokalaemia. However, in the far larger subset of the hypertensive population who do not fit into these criteria, the evidence for screening is conflicting and dependent on the disease prevalence. The purpose of this study was to examine the prevalence of PHA in a large population with mild to moderate hypertension and without hypokalaemia using a carefully controlled study protocol including a normotensive control population. Hypertensive subjects underwent medication washout and both hypertensive and normotensive subjects placed on a high-sodium diet prior to biochemical and haemodynamic testing. Study specific cutoff values were based on results from the normotensive population studied under identical conditions. A screening test (serum aldosterone/PRA ratio [ARR]425 with a serum aldosterone level 48 ng/dl) was followed by a confirmatory test (urine aldosterone excretion rate [AER] 417 lg/ 24 h) to demonstrate evidence of PHA. An elevated ARR with a concomitant elevated serum aldosterone was present in 26 (7.5%) individuals. Of these, 11 (3.2%) had an elevated AER, consistent with evidence of PHA. Individuals with PHA had higher blood pressure and lower serum potassium levels while on a high-sodium diet. Sodium restriction neutralized these differences between PHA and essential hypertensives. The prevalence of PHA in this mild to moderate hypertensive population without hypokalaemia is at most 3.2%, a rate that might lead to excessive false positives with random screening in comparable populations. Hyperaldosteronism, when present, is responsive to sodium restriction.

show abstract

“…In a study of more than 50 hypertensive subjects who were classified as nonmodulators or normally modulating, 85% of the non-modulators had a positive family history for hypertension when compared with only 30% of the normally modulating hypertensive patients. 12 In a large number of normotensive kidney donors in whom family history for hypertension was carefully assessed, those individuals with a positive family history were three to four times more likely to have the characteristics of non-modulation than were those who had a negative family history. 21 Finally, in familial studies where the presence or absence of non-modulation was assessed in more than one individual in the family, non-modulation was nine times more likely to be associated with a positive rather than a negative family history for hypertension.…”

Section: Discussionmentioning

confidence: 99%

Red blood cell lithium-sodium countertransport in non-modulating essential hypertension.

et al. 1989

View full text Add to dashboard Cite

Abnormalities in erythrocyte Li-Na countertransport have been reported in hypertensive subjects, and the available evidence favors familial aggregation and striking heritability of this marker. It is uncertain, however, whether the abnormalities are associated with hypertension per se or whether they may be concentrated in a particular subset of hypertensive subjects. In the present study, maximal rates of Li-Na countertransport were measured in red blood cells of 82 white subjects, including 37 normotensive subjects and 45 normal-or high-renin hypertensive subjects previously classified as non-modulators (n=21) or modulators (n=24). Mean countertransport activity was significantly higher in non-modulators compared with normally modulating hypertensive or normotensive subjects (0.475±0.044 vs. 0.309±0.028 or 0.249+0.012 mmol/1 cellxhr, respectively, p<0.001). Modulators did not differ significantly from normotensive subjects with regard to mean countertransport activity. Red blood cell sodium pump and Na-K-Cl cotransport were not significantly different in modulating and non-modulating hypertensive subjects. These relations remained unchanged after adjusting for age, body weight, and plasma cholesterol levels by analysis of covariance. A countertransport value exceeding 0.50 mmol/1 cellxhr occurred in 40% of the non-modulators but in only one of the other subjects. In contrast, while one half of the modulators and normotensive subjects had a countertransport value less than 0.235 mmol/1 cellxhr, none of the non-modulators did. Thus, elevated countertransport appears to aggregate in the non-modulating subset of essential hypertensive subjects. If these findings are cautiously applied, selecting patients with an elevated countertransport activity (>0.50 mmol/1 cellxhr) may serve as a useful method for enriching a sample of the essential hypertensive population with patients who have the non-modulation trait. (Hypertension 1989;13:721-726)

show abstract

Abnormal Renal Sodium Handling in Essential Hypertension. Relation to Failure of Renal and Adrenal Modulation of Responses to Angiotensin II

Cited by 41 publications

References 0 publications

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

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

Prevalence of primary hyperaldosteronism in mild to moderate hypertension without hypokalaemia

Red blood cell lithium-sodium countertransport in non-modulating essential hypertension.

Contact Info

Product

Resources

About