Normotensive Phase Research Articles

CORRIGENDUM.

CorrigendumCORRIGENDUMPublished Online:08 Jul 2019https://doi.org/10.1152/ajprenal.zh2-8726-corr.2019Original articleMoreSectionsPDF (76 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Williams CR, Mistry M, Cheriyan AM, Williams JM, Naraine MK, Ellis CL, Mallick R, Mistry AC, Gooch JL, Ko B, Cai H, Hoover RS. Zinc deficiency induces hypertension by promoting renal Na+ reabsorption. Am J Physiol Renal Physiol 316: F646–F653, 2019. First published January 16, 2019; doi:10.1152/ajprenal.00487.2018.—In this article, in terms of experimental procedures, mice were group housed for metabolic cage studies; for the results, there are some data for urinary values where the units have to be corrected. These changes did not alter any of the conclusions of the study. Corrections are detailed below.In experimental design, BP Regulation, Na+ excretion, the paragraph should read as follows:Metabolic cage studies were performed to measure urinary Na+ excretion. Mice were group housed (5 mice/cage). After a 24-h acclimation period, 24-h urine samples were collected. Na+ was measured using a Medica EasyLyte Plus Na K Cl analyzer. Total Na+ excretion was calculated by multiplying Na+ concentration by total urine output/24 h/cage.In results, ZnD Causes Increased BP and Dysregulated Renal Na+ Transport, the second paragraph should read as follows:Concurrently, 24-h urinary Na+ excretion was measured (Fig. 1D). BP changes were accompanied by corresponding changes in urinary Na+ excretion. During the pressor phases, urinary Na+ levels were significantly decreased in ZnD mice at week 1 (836.3 ± 87.76 vs. 1,198.4 ± 62.52 µmol) and week 6 (937.0 ± 53.54 vs. 1,338.0 ± 144.40 µmol) compared with ZnA mice. However, during the normotensive phase, urinary Na+ levels were not statistically different at week 3 (1,092.4 ± 76.36 vs. 1,140.1 ± 84.35 µmol). Like urinary Na+ excretion, the amount of Cl− excreted during the pressor phases was less in ZnD mice (863.9 ± 64.30 vs. 1,135.7 ± 59.84 µmol at week 1 and 950.7 ± 49.34 vs. 1,400.5 ± 180.8 µmol at week 6), while urinary Cl− levels were unaltered during the normotensive phase (1,078.2 ± 66.55 vs. 1,167.5 ± 90.53 µmol at week 3). However, urinary K+ excretion was reduced during all phases (616.0 ± 57.43 vs. 824.4 ± 38.99 µmol at week 1, 625.6 ± 46.46 vs. 826.7 ± 49.61 µmol at week 3, and 593.9 ± 19.29 vs. 963.3 ± 89.80 µmol at week 6). Together, these results indicate that ZnD-induced BP increases are accompanied by reduced renal Na+, Cl−, and K+ excretion.Download figureDownload PowerPointIn results, NCC Mediates ZnD-Induced Hypertension, first paragraph, the final sentences should read as follows:Furthermore, urinary Na+ levels were elevated in response to HCTZ administration compared with vehicle-treated ZnD mice (1,227.7 ± 29.58 vs. 1,032.5 ± 30.39 µmol). This finding indicates an increase in NCC activity.In results, Zn2+ Regulates BP and NCC, first paragraph, the final sentence should read as follows:Furthermore, this reduction in BP was accompanied by elevated urinary Na+ levels (1,280.9 ± 31.92 vs. 937.0 ± 75.72 µmol).The corrected values are shown in Fig. 1D, below:The corrected values are also shown in Fig. 2, B and F, below:Download figureDownload PowerPointThis article has no references to display. Download PDF Previous Back to Top FiguresReferencesRelatedInformation Related ArticlesZinc deficiency induces hypertension by promoting renal Na+ reabsorption 21 Mar 2019American Journal of Physiology-Renal Physiology More from this issue > Volume 317Issue 1July 2019Pages F218-F219 Copyright & PermissionsCopyright © 2019 the American Physiological Societyhttps://doi.org/10.1152/ajprenal.zh2-8726-corr.2019PubMed31282741History Published online 8 July 2019 Published in print 1 July 2019 Metrics

Importance of ambulatory blood pressure monitoring in the diagnosis and prognosis of pediatric hypertension

The prevalence of high blood pressure (BP) at pediatric age has increased progressively, one of the causes of which is obesity. However, the dominant etiology in this age group is renal and/or cardiovascular pathology. Ambulatory blood pressure monitoring (ABPM) is the method of choice for the diagnosis of hypertension, especially in children at high cardiovascular risk. Its use is limited to children from five years of age. Choosing appropriate cuff size is key to obtaining correct blood pressure. The main indication for ABPM is to confirm the diagnosis of hypertension. It also allows the diagnosis of white coat hypertension (which may represent an intermediate stage between the normotensive phase and hypertension), or masked hypertension, associated with progression to sustained hypertension and left ventricular hypertrophy (LVH). Children with isolated nocturnal hypertension should be considered as having masked hypertension. BP load is defined as the percentage of valid measurements above the 95th percentile for age, gender, and height. Values above 25-30% are pathological and those above 50% are predictive of LVH. ABPM correlates with target organ damage, particularly LVH and renal damage. It is useful in the differentiation of secondary hypertension, since these children show higher BP load and less nocturnal dipping, and confirmation of response to therapy. Thus ABPM allows the diagnosis and classification of hypertension, provides cardiovascular prognostic information and identifies patients with intermediate phenotypes of hypertension.

Abstract 413: Renal Cyclooxygenase-2 Expression And Hemodynamic Role During Angiotensin II-dependent Hypertension

Intrarenal cyclooxygenase-2 (COX-2) activity is increased during activation of the renin-angiotensin-system (RAS) increasing synthesis of prostaglandin E2 (PGE2) and buffering the vasoconstrictor and antinatriuretic effects of angiotensin II (AngII). While AngII upregulates intrarenal COX-2 expression, it remains unclear if this occurs in a time-dependent manner, thereby impacting renal hemodynamics differently during the early and late phases of the development of high blood pressure in AngII-induced hypertension. Male Sprague-Dawley rats were infused with AngII (0.4 μg/min/kg). Systolic blood pressure (SBP), COX-2 expression and PGE2 tissue content and urinary excretion were evaluated at day 3, 7 and 14 of the AngII infusions. In acute studies we evaluated the effects of COX-2 inhibition at day 5-7 and day 14 on renal hemodynamic parameters. Chronic AngII infusions increased SBP from day 7 through 14: 162 ± 5 mmHg; and 198 ± 15 mmHg versus controls: 114 ± 10 mmHg; P<0.05. COX-2 mRNA and protein levels were high in kidney cortex only at day 3 (mRNA: 241 ± 56%, protein: 160 ± 21%, P<0.05 versus controls). Medullary COX-2 mRNA and protein were increased on days 3 (mRNA: 176 ± 20%, protein: 185 ± 32%, P<0.05 versus controls), 7 (mRNA: 189 ± 23%, protein: 158 ± 15%, P<0.05 versus controls) and 14 (mRNA: 148 ± 15%, protein: 135 ± 13%, P<0.05 versus controls). Urinary and medullary PGE2 increased by day 3 and remained elevated during days 7 and 14. COX-2 inhibition decreased GFR and renal blood flow in AngII infused rats during both the early and late phases. Interestingly, COX-2 inhibition decreased mean arterial blood pressure at day 14 of AngII-infusion (COX-2 inhibition: 124 ± 9 versus 140 ± 7 mmHg, P<0.05) but not during the early normotensive phase (COX-2 inhibition: 110 ± 4 versus 115± 4 mmHg, P=NS). These results indicate that enhanced medullary COX-2 expression and PGE2 production during both the early and late phases attenuates the effects of AngII on renal hemodynamics. However COX-2 inhibition at day 14 reduced blood pressure, suggesting that a vasoconstrictor COX-2 metabolite contributes to the hypertension during the late phase.

Reactivity in resistant arteries of SHR treated with anti‐TLR4 antibody

Recent reports indicate that TLR4 participates in mediating the inflammatory responses in vascular diseases. Because hypertension is considered a chronic inflammatory disease, our hypothesis is that TLR4 expression is increased in arterioles of spontaneously hypertensive rats (SHR) and participates of vascular dysfunction present in hypertension. For this, SHR were treated with anti‐TLR4 antibody and we analyzed reactivity in mesenteric arterioles. TLR4 expression is increased in mesenteric arterioles from SHR with 15 weeks‐old (hypertensive phase) versus SHR 5 weeks‐old (normotensive phase). The treatment of SHR 15 weeks‐old for 15 days with losartan decreased TLR4 expression in mesenteric arterioles. Anti‐TLR4 treatment decreased blood pressure of SHR. In vascular reactivity, the maximum response of mesenteric arterioles to noradrenaline was decreased in SHR anti‐TLR4‐treated compared to untreated rats. The mechanisms involved are COX‐1 and COX‐2 dependent. There was no difference in relaxation response to vasodilatation agonists after the treatment. It was also found a decreased in IL‐6 secretion in SHR serum after anti‐TLR4 treatment. We suggest that TLR4 has a role in the low‐grade inflammatory process present in hypertension and in vascular dysfunction present in SHR.

Salt and Fluid Intake in the Development of Hypertension in Peritoneal Dialysis Patients

Background. Although fluid overload contributes to hypertension in CAPD patients, less attention has been paid to the role of excess salt and fluid intake. Therefore, we investigated the role of salt and fluid intake in the development of hypertension in CAPD patients. Methods. A total of 165 stable CAPD patients were included into this study. Based on the blood pressure in three consecutive months, they were divided into three groups: persistent hypertensive (PH; n = 33), intercurrent hypertensive (IH; n = 58) and persistent normotensive (PN; n = 74). The IH group was further divided into two phases: normotensive and hypertensive. Fluid status was evaluated by clinical assessment and bioimpedance analysis (BIA). Results. There were no differences in age, gender, and duration of dialysis among groups. Patients were more fluid overloaded in the PH group. Extracellular water (ECW), total body water (TBW), and normalized extracellular water by height (NECW) were higher in the PH group than the PN group (16.77 ± 3.62 L vs. 14.61 ± 2.92 L for ECW, p < 0.01; 32.22 ± 8.23 L vs. 28.98 ± 6.00 L for TBW, p < 0.05; and 10.28 ± 1.86 L/m vs. 9.08 ± 1.63L/m for NECW, p < 0.01). However, patients in the PH group also had more total fluid removal (TFR) and total sodium removal (TSR) compared with the PN group (1346.82 ± 431.27 mL/d vs. 1139.28 ± 412.65 mL/d for TFR, p < 0.05; and 141.52 ± 61.57 mmol/d vs. 102.42 ± 62.51 mmol/d for TSR, p < 0.01). The same trend was demonstrated when compared values of hypertensive and normotensive phase in IH group; patients had higher ECW, TBW, NECW, TSR, and PNa when they were in hypertensive phase than in the normotensive phase. Conclusions. This study confirmed that fluid overload was closely associated with the development of hypertension in CAPD patients. It also showed that hypertensive patients were in general more fluid overloaded despite a higher fluid and sodium removal as compared with normotensive patients.

Defense reaction alters the response to blood loss in the conscious rabbit.

The interaction of sensory stressors with the cardiovascular response to blood loss has not been studied. The cardiovascular response to a stressor (i.e., the defense reaction) includes increased skeletal muscle blood flow and perhaps a reduction in arterial baroreflex function. Arterial pressure maintenance during blood loss requires baroreflex-mediated skeletal muscle vasoconstriction. Therefore, we hypothesized that the defense reaction would limit arterial pressure maintenance during blood loss. Male, New Zealand White rabbits were chronically prepared with arterial and venous catheters and Doppler flow probes. We removed venous blood in conscious rabbits until mean arterial pressure decreased to <40 mmHg. We repeated the experiment with (air) and without (sham) simultaneous exposure to an air jet stressor. Air resulted in a defense reaction (e.g., mean arterial pressure = 94 +/- 1 and 67 +/- 1 mmHg for air and sham, respectively). Contrary to our hypothesis, air increased the blood loss necessary to produce hypotension (19.3 +/- 0.2 vs. 16.9 +/- 0.2 ml/kg for sham). Air did not reduce skeletal muscle vasoconstriction during normotensive hemorrhage. However, air did enhance renal vasoconstriction (97 +/- 3 and 59 +/- 3% of baseline for sham and air, respectively) during the normotensive phase. Thus the defense reaction did not limit but rather extended defense of arterial pressure during hemorrhage.

Coronary and systemic hemodynamic effects of clevidipine, an ultra-short-acting calcium antagonist, for treatment of hypertension after coronary artery surgery.

The aim was to evaluate the use of clevidipine, a new vascular selective, ultra-short-acting calcium antagonist for blood pressure control after coronary artery bypass grafting (CABG). The effects of clevidipine on central hemodynamics, myocardial blood flow and metabolism were studied at two different phases after CABG. In phase 1 (n=13), the hypertensive phase, the effects of clevidipine were compared to those of sodium nitroprusside (SNP) when used to control postoperative hypertension. In phase 2 (n=9), the normotensive phase, a clevidipine dose-response relationship was established. At a target mean arterial pressure (MAP) of 75 mmHg, systemic vascular resistance (SVR) and heart rate (HR) were lower, preload, stroke volume (SV) and pulmonary vascular resistance (PVR) were higher, while there were no differences in myocardial lactate metabolism or oxygen extraction with clevidipine compared to SNP. In the normotensive phase, clevidipine induced a dose-dependent decrease in MAP (-19%), SVR (-27%) and PVR (-15%), accompanied by an increase in SV (10%), but no reflex increase in HR or changes in cardiac preload. Clevidipine caused a direct coronary vasodilation, as indicated by a decrease in myocardial oxygen extraction from 54% to 45%. Myocardial lactate metabolism was unaffected by clevidipine. The blood clearance of clevidipine was 0.05 l x min(-1) x kg(-1), the volume of distribution at steady state was 0.08 l x kg(-1) and the initial and terminal half-lives were <1 min and 4 min, respectively. Clevidipine rapidly reduced MAP and induced a systemic, pulmonary and coronary vasodilation with no effect on venous capacitance vessels or HR. Clevidipine caused no adverse effects on myocardial lactate metabolism. Clevidipine thus appears suitable to control blood pressure after CABG.

Effect of diazepam on endocrine and cardiovascular responses to head-up tilt in humans.

Effects of the GABAergic drug diazepam (0.15 mg kg-1, i.v.) on cardiovascular and endocrine responses to 50 degrees head-up tilt were evaluated in seven men. During the initial phase of tilt (normotensive phase), increases in heart rate (HR) and total peripheral resistance (TPR) and decreases in cardiac output were unaffected by diazepam. Also the associated increase in plasma noradrenaline did not change, while response in plasma ACTH was diminished and in plasma cortisol abolished by diazepam (F(1,10) = 6.45; P < 0.03). After 42 +/- 4 min of sustained tilt with saline (control) and 47 +/- 6 min (n.s.) after diazepam, presyncopal symptoms appeared (hypotensive phase) associated with decreases in HR, MAP, and TPR (P < 0.01). This episode induced a 2-3-fold increase in plasma ACTH, beta-endorphin, prolactin, cortisol (< 0.01), and a moderate increase in plasma adrenaline (P < 0.05). Diazepam did not significantly change cardiovascular and endocrine responses to the hypotensive phase of tilt. Results indicate that diazepam attenuates the cortisol part of pituitary-adrenal responses to moderate, but not to severe, central hypovolaemia in humans with no effect on cardiovascular tolerance.

Pituitary-adrenal responses to head-up tilt in humans: effect of H1- and H2-receptor blockade.

Effects of the histamine H1- or H2-receptor antagonists mepyramine (Mep) and cimetidine (Cim) on neuroendocrine and cardiovascular responses to 50 degrees head-up tilt were evaluated in seven human males. Central hypovolemia was characterized by two phases. The first is a normotensive phase with increases in heart rate (HR), total peripheral resistance (TPR), and decrease in cardiac output. Plasma adrenocorticotropic hormone, beta-endorphin, cortisol, catecholamines, and renin activity increased moderately. Normotension lasted 39 +/- 7 min during infusion of saline but was reduced by Mep [18 +/- 3 min, F(2,12) = 9.60, P less than 0.01] and was unaffected by Cim (44 +/- 4 min). The second is a hypotensive phase associated with presyncopal symptoms (hypovolemic shock) and decreases in HR and TPR and a further increase in pituitary-adrenal and sympathoadrenal activity. Decreases in mean arterial pressure and TPR were augmented by Mep, which inhibited release of norepinephrine. Cim inhibited epinephrine release without affecting the development of hypovolemic shock. It is concluded that histaminergic mechanisms are involved in activation of the sympathoadrenal system but not in the pituitary-adrenal axis during central hypovolemia in humans.

Free and conjugated plasma catecholamines in hypertensive patients with and without pheochromocytoma.

SUMMARY A total of 17 hypertensive patients suspected of having a pheochromocytoma underwent venous catheterization to determine their free and conjugated plasma catecholamines (CA). Six of the patients were found to have a pheochromocytoma; the seventh, an adrenomedullary hyperplasia. The venous outflow from the site adjacent to toe tumor, when compared to the respective site of sampling in essential hypertensive patients, was characterized by a very high outflow of free (and sometimes an absence of conjugated) CA that resulted in an abnormally high ratio of free-to-conjugated CA; the CA conjugates themselves were rarely elevated. Venous sampling at the peripheral site showed that at the height of the paroxysms, the peripheral venous system in these patients was flooded by free norepinephrine (NE) or epinephrine (E); and by free dopamlne (DA) in another patient who had low blood pressure. The three patients with the most peripheral "flooding" by free CA at the height of the paroxysm had, even In toe normotensive phase, lower conjugated plasma NE + E (p < 0.01), DA (p < 0.05), and higher urinary vanillylmandelic add (VMA) excretion (p < 0.02) than the other three patients; one of the latter had only conjugated catecholamines, extremely elevated, during paroxysms. The subgroups with low and high conjugates could not be clearly separated clinically, but two of the three patients with high conjugates had less frequent crises. The patient with the adrenomedullary hyperplasia had unremarkable changes in free CA; only the finding of elevated conjugated CA suggested the possibility of adrenomedullary hyperfunction. Conjugation appears to be one of the major inactivation pathways of CA released from a pheochromocytoma. Patients with low levels of conjugates are more susceptible to a sudden overflow of free CA without a concomitant rise of conjugated CA and to have a higher VMA excretion than patients with high concentrations of conjugated CA. The type of CA, however, is eventually decisive for the clinical presentation, notwithstanding the extent of conjugation. The presence of high levels of conjugated CA may suggest adrenomedullary hyperfunction even in the absence of other diagnostic criteria. (Hypertension 2: 177-186, 1980)

Free and Conjugated Plasma and Urinary Dopamine in Human Hypertension*

ABSTRACT Plasma and urinary free and conjugated dopamine (DA) were determined, with the use of a new method of hydrolysis of conjugated catecholamines, in 29 patients with essential hypertension (EH), 4 with primary aldosteronism (PA), and 3 with phaeochromocytoma (normotensive phase), as well as in 16 control subjects. Plasma free DA is not detectable in most subjects. Mean conjugated plasma DA was found to be significantly elevated in EH, PA, and phaeochromocytoma patients [1.97 ± 0.3, 3.1 ± 0.3, and 3.3 ± 1.2 (SE) ng/ml, respectively, vs. 0.98 ± 0.1 ng/ml in control subjects]. Urinary free DA was lower in EH patients than in PA subjects. Total urinary DA was higher in PA patients than in control and EH subjects. After iv furosemide, there was less increase in the urinary excretion of sodium (P < 0.05) and free DA (P < 0.005) in EH patients than in controls. The elevated urinary free and total DA excretions in PA patients returned toward normal when their adrenal adenomas were removed. The elevated plas...

Increased catecholamine excretion during normotensive phase in paroxysmal type of pheochromocytoma.

Seven patients with paroxysmal type of pheochromocytoma were studied from the diagnostic point of view, because diagnosis of this type of pheochromocytoma may be difficult if the patient was seen during attackfree period. Comparison of catecholamine levels in timed urine specimens before and after histamine test was made. A clear increase of catecholamine excretion was found after histamine provocation, however, significantly high concentration of the amine was observed in all normotensive control urine specimens. Histamine test was hazardous and tyramine test was less valuable as a provocation test in patient with paroxysmal type. From these findings, we concluded that no more provocation test was necessary for the screening purpose. Catecholamine assay using 1 hour urine specimen could be valuable for establishing the diagnosis of pheochromocytoma, because of its accuracy and safety.

Diagnostic procedures for pheochromocytoma; technique of assay of urine in rat and demonstration of piperoxan hydrochloride; antidiuresis during normotensive phase.

This report demonstrates the usefulness of two diagnostic procedures in the normotensive phase of pheochromocytoma with paroxysmal hypertension. One of these—approximate assay of the pressor activity of the urine in the rat—has not been described as such, although similar assays in a cat that has been injected with ergotamine have been shown to be of diagnostic value. 1 The other procedure is the demonstration of an antidiuretic effect of piperoxan hydrochloride during the normotensive phase of the disease. This effect of piperoxan had previously been observed only in patients with hypertension due to pheochromocytoma and in normal subjects given pressor doses of epinephrine and arterenol. The question whether the decreased arterial pressure would affect the antidiuresis was unanswered, and we doubted that the test would be useful in the normotensive phase of pheochromocytoma. 2 Report of a Case A 22-year-old man had been medically discharged from the U. S. Army