Age-related hypertension and salt sensitivity are associated with unique cortico-medullary distribution of D1R, AT1R, and NADPH-oxidase in FBN rats

Pokkunuri, Indira; Chugh, Gaurav; Rizvi, Imran; Asghar, Mohammad

doi:10.3109/10641963.2014.977489

Cited by 15 publications

(18 citation statements)

References 42 publications

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“…It is also possible that hypomagnesemia in TRPM7Δkinase mice may influence endothelial function, since decreased [Mg 2+ ] i enhances agonist-stimulated vasoconstriction and impairs vasodilation, while increased [Mg 2+ ] i is associated with vasorelaxation. These effects may occur through Mg 2+ interactions with Ca 2+ , or through eNOS modulation by Mg 2+ (46). …”

Section: Discussionmentioning

confidence: 99%

Transient Receptor Potential Melastatin 7 Cation Channel Kinase

Antunes

Callera

et al. 2016

Hypertension

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Transient receptor potential melastatin 7 (TRPM7) is a bi-functional protein comprising a magnesium (Mg2+)/cation channel and a kinase domain. We previously demonstrated that vasoactive agents regulate vascular TRPM7. Whether TRPM7 plays a role in the pathophysiology of hypertension and associated cardiovascular dysfunction is unknown. We studied TRPM7kinase-deficient mice (TRPM7Δkinase) (heterozygous for TRPM7kinase) and wildtype (WT) mice infused with Ang II (400 ng/kg/min, 4 weeks). TRPM7kinase expression was lower in heart and aorta from TRPM7Δkinase versus WT mice, effects that were further reduced by Ang II infusion. Plasma Mg2+ was lower in TRPM7Δkinase versus WT mice in basal and stimulated conditions. Ang II increased blood pressure in both strains with exaggerated responses in TRPM7Δkinase versus WT groups (p<0.05). Acetylcholine-induced vasorelaxation was reduced in Ang II-infused TRPM7Δkinase mice, an effect associated with Akt and eNOS downregulation. Vascular VCAM-1 expression was increased in Ang II-infused TRPM7kinase-deficient mice. TRPM7 kinase targets, calpain and annexin-1, were activated by Ang II in WT but not in TRPM7Δkinase mice. Echocardiographic and histopathological analysis demonstrated cardiac hypertrophy and LV dysfunction in Ang II-treated groups. In TRPM7kinase-deficient mice, Ang II-induced cardiac functional and structural effects were amplified compared with WT counterparts. Our data demonstrate that in TRPM7Δkinase mice, Ang II-induced hypertension is exaggerated, cardiac remodelling and LV dysfunction are amplified and endothelial function is impaired. These processes are associated with hypomagnesemia, blunted TRPM7kinase expression/signaling, eNOS downregulation and pro-inflammatory vascular responses. Our findings identify TRPM7kinase as a novel player in Ang II-induced hypertension and associated vascular and target organ damage.

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Section: Discussionmentioning

confidence: 99%

Transient Receptor Potential Melastatin 7 Cation Channel Kinase

Antunes

Callera

et al. 2016

Hypertension

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“…A high‐salt intake enhances renal injury due to increased oxidative stress in hypertensive as well as normotensive rats. In addition, it has been reported that the small GTPase Rac 1, a regulatory subunit of NADPH oxidase, is activated by elevated NaCl, and Rac1 inhibitor blocks NaCl‐induced superoxide generation …”

Section: Introductionmentioning

confidence: 99%

Early urinary biomarkers of renal tubular damage by a high‐salt intake independent of blood pressure in normotensive rats

Washino

Hosohata

Jin

et al. 2017

Clin Exp Pharma Physio

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Dietary sodium intake has been associated with progression to chronic kidney disease (CKD) as well as hypertension. A high-salt intake causes renal damage independent of hypertension. Because traditional renal biomarkers are insensitive, it is difficult to detect renal injury induced by a high-salt intake, especially in normotensive patients. Here, we investigated whether newly developed renal biomarkers could be detected earlier than traditional biomarkers under a high-salt intake, in normotensive rats. Male Wistar Kyoto rats (WKY) received a regular (0.8% NaCl) or salt-loaded (2, 4, and 8% NaCl) diet from 9 to 17 weeks of age. A urine sample was obtained once a week and urinary vanin-1, neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (Kim-1) were measured. At 17 weeks of age, 8% salt-loaded WKY showed histopathological renal tubular damage and elevated Rac1 activity in renal tissues. Although there was no significant increase in serum creatinine, urinary albumin, N-acetyl-β-D-glucosaminidase (NAG), or Kim-1 during the study period among the groups, urinary vanin-1 and NGAL significantly increased in 8% salt-loaded WKY from 10 to 17 weeks of age. These results suggest that urinary vanin-1 and NGAL, which might be induced by salt per se, are potentially earlier biomarkers for renal tubular damage in normotensive rats under a high-salt intake.

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“…A high amount of epicardial fat is dangerous because this fat tissue is known to have unique endocrine and paracrine functions which affect the cardiac autonomic system [ 11 – 13 ]. Because elevated BP is associated with ectopic fat accumulation in the intrathoracic and epicardial areas, an association between epicardial adipose tissue and hypertension [ 14 , 15 ], as well as with diurnal BP patterns, [ 16 , 17 ] has been suggested in some recent studies. However, the association between EFT and autonomic function assessed by HRR in patients with hypertension has not been well studied.…”

Section: Introductionmentioning

confidence: 99%

Association among epicardial fat, heart rate recovery and circadian blood pressure variability in patients with hypertension

Kim

Cho

et al. 2015

Clin Hypertens

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BackgroundEpicardial fat tissue is known to have an unique endocrine function which affect the cardiac autonomic system. Heart rate recovery (HRR) is a simple non-invasive measurement that assesses autonomic nervous system dysfunction. We aimed to investigate the association among epicardial fat thickness (EFT), HRR and circadian blood pressure (BP) variation in patients with hypertension.MethodsA total of 358 consecutive patients who underwent both 24-hour ambulatory BP monitoring (ABPM) and a treadmill test were enrolled. Echocardiographic EFT and HRR, defined as peak heart rate minus heart rate after a 1-min recovery time, were measured. Patients were classified according to the ABPM; 147 patients with hypertension with a dipping pattern at night (dippers), 140 patients with hypertension with a non-dipping pattern at night (non-dippers) and 71 normotensive controls.ResultsEFT was significantly higher in hypertensive patients, especially in the non-dipper group, compared to the controls (non-dippers, 7.5 ± 2.9 mm; dippers, 6.6 ± 1.6 mm; controls, 5.5 ± 2.1 mm; p < 0.001). HRR was significantly lower in both hypertensive groups as compared to the control group and was the lowest in the non-dipper group (non-dipper, 26.6 ± 18.6; dipper, 29.5 ± 21.5; control, 71.4 ± 19.8; p < 0.001). EFT was significantly correlated with age, body mass index, 24-hour mean systolic BP and 24 h mean BP variability, whereas exercise duration, metabolic equivalents (METs) and HRR were inversely correlated with EFT. Furthermore, EFT > 6.7 mm was associated with a blunted HRR with 76 % sensitivity and 61 % specificity (ROC area under curve: 0.71, 95 % confidence interval, CI = 0.65–0.76, p < 0.001). In a multivariate analysis, EFT (odds ratio, OR = 3.53, 95 % CI = 1.20–10.37, p = 0.022) and 24-hour mean BP variability (OR = 1.09, 95 % CI = 1.03–1.16, p = 0.005) were independent predictors of a blunted HRR defined as HRR ≤ 12 beats (n = 63) in patients with hypertension.ConclusionEFT and HRR were significantly correlated with circadian BP variability in patients with hypertension. EFT and circadian BP variability were independent predictors of blunted HRR, which suggests a link between epicardial fat and autonomic dysregulation in hypertension.

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Age-related hypertension and salt sensitivity are associated with unique cortico-medullary distribution of D1R, AT1R, and NADPH-oxidase in FBN rats

Cited by 15 publications

References 42 publications

Transient Receptor Potential Melastatin 7 Cation Channel Kinase

Transient Receptor Potential Melastatin 7 Cation Channel Kinase

Early urinary biomarkers of renal tubular damage by a high‐salt intake independent of blood pressure in normotensive rats

Association among epicardial fat, heart rate recovery and circadian blood pressure variability in patients with hypertension

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