bluuebunny/crossref_metadata_2025 huggingface dataset:
Opposite Effects of Remodeling and Hypertrophy on Arterial Compliance in Hypertension
Authors: Mourad Jean-Jacques , Girerd Xavier , Boutouyrie Pierre , Safar Michel , Laurent Stéphane
Published: June 2012

Sustained hypertension is associated with a reduction in large artery compliance. However, we previously showed that, at the site of the radial artery, a distal muscular artery, the compliance of hypertensive patients was not significantly different from those of normotensive controls when the two groups were studied at their respective mean arterial pressures, despite increased wall thickness in hypertensives. To determine whether this paradoxical finding could be related to a specific pattern of geometrical changes, we studied arterial compliance in never-treated hypertensive patients characterized either by radial artery hypertrophy or remodeling, and compared them to normotensive controls. By analogy with Devereux’s classification for left ventricular hypertrophy, we defined remodeling as an increased thickness to radius ratio (h/r) and a normal vascular mass (VM), and arterial hypertrophy as an increased VM irrespective of the values of h/r. Internal diameter and wall thickness were measured at the site of the radial artery using a high resolution echo-tracking system. The lumen cross-section-pressure curve was determined from the two simultaneous and continuous recordings of arterial diameter and blood pressure. Then, the cross-sectional compliance (CC) pressure curve was calculated. Isobaric compliance was calculated at 100 mm Hg. Thresholds for h/r and VM were determined according to gender as the 95th percentile of a group of 100 normotensive subjects. The group of hypertensive patients included 58 patients with hypertrophy (h/r: 0.25±0.04;VM: 31±6 mg/cm; mean±SD) and 25 patients with remodeling (h/r: 0.29±0.06;VM: 20±4 mg/cm) and was compared to a group of 50 age- and gender-matched normotensives (h/r: 0.16±0.02;VM: 17±4 mg/cm). Compared to normotensives, isobaric compliance of the radial artery was increased in hypertensive patients with hypertrophy (HH) whereas it was not different in hypertensive patients with remodeling (RH). These results indicate that compliance is dependent on hypertrophy or remodeling pattern and suggest that in the face of hypertension, only arterial hypertrophy is an adaptive process leading to normal operating compliance through an increased isobaric compliance.
Modulation of Blood Pressure in the Dahl SS/jr Rat by Embryo Transfer
Authors: Kubisch H. Michael , Mathialagan Sumathy , Gómez-Sánchez Elise P.
Published: June 2012

Gestational hypertension and malnutrition are associated with hypertension and ischemic heart disease in the adult human. The impact of the gestational environment on the adult blood pressure in two well-characterized genetically homogeneous rat strains, the hypertensive SS/jr and normotensive SR/jr, was studied by cross-fostering within 6 hours of birth and by embryo transplantation with the recipient dam nursing the transplanted pups. Systolic blood pressure (BP) was measured by tail-cuff plethysmography twice a week after the age of 7 weeks. The lactational environment (cross-fostering) had no effect on blood pressure. Embryo transfer between like strains had no effect on the development of hypertension, nor did the BP of R transferred to S (RetS) differ from that of normal R or RetR. At 7 weeks of age, the BP of SetR was significantly lower than that of S or SetS (
P
<.01) and was similar to that of RetR and R. With age, the blood pressures of the S, SetS and SetR increased at approximately the same rate but from a significantly different baseline. Salt-sensitivity in the S and resistance in the R were not altered. The protective effect of the R gestational environment on SetR female BP was abrogated during whelping and lactation. Embryo transfer and cross-fostering did not alter the weight of rats older than 7 weeks. Because the BP of the R dams were significantly lower than that of the S dams, these studies do not distinguish between the effects of the R dams’ lower blood pressure per se and hormonal influences of the R uterus on the S blood pressure phenotype.
Dissociation Between Muscle and Skin Sympathetic Nerve Activity in Essential Hypertension, Obesity, and Congestive Heart Failure
Authors: Grassi Guido , Colombo Manuela , Seravalle Gino , Spaziani Domenico , Mancia Giuseppe
Published: June 2012

Abstract
—Essential hypertension, obesity, and congestive heart failure are characterized by an increase in muscle sympathetic nerve activity. Whether in these conditions skin sympathetic nerve activity is also increased has never been systematically examined, however. In 10 untreated mild essential hypertensive, 12 untreated normotensive obese, 10 mild (New York Heart Association class II) heart failure, and 10 normotensive lean healthy control subjects, we measured beat-to-beat arterial blood pressure (Finapres technique), body mass index, and postganglionic sympathetic nerve activity in skeletal muscle and skin areas (microneurographic technique, peroneal nerve). The muscle and skin nerve measurements were made in a randomized sequence. All data were obtained with the subject supine in a quiet, semidark environment at constant temperature over two periods of 30 minutes each, separated by a 20- to 30-minute interval. Blood pressure was increased only in hypertensive and body mass index only in obese subjects. Muscle sympathetic nerve activity quantified as bursts/min was markedly and significantly (
P
<.01) greater in essential hypertensive (33.3±1.7), obese (42.2±2.8), and congestive heart failure subjects (55.8±4.3) in comparison with control subjects (23.9±1.6). This was the case also for muscle sympathetic nerve activity, quantified as bursts per 100 heart beats. In contrast, skin sympathetic nerve activity (bursts per minute) was superimposable in hypertensive, obese, heart failure, and control subjects, its ability to increase being documented in all four groups by the marked response to an acoustic stimulus. Thus, in various diseases, muscle but not skin sympathetic activity is increased, with the sympathetic activation not being uniformly distributed over the whole cardiovascular system.
Relationship Between Extreme Dippers and Orthostatic Hypertension in Elderly Hypertensive Patients
Authors: Kario Kazuomi , Eguchi Kazuo , Nakagawa Yukinori , Motai Keiji , Shimada Kazuyuki
Published: June 2012

Abstract
—Among elderly hypertensive subjects, extreme dippers with marked nocturnal fall in blood pressure (BP) as well as nondippers with absent nocturnal fall in BP are more prone to cerebrovascular disease when compared with those with appropriate nocturnal BP fall. However, the relationship between these abnormal diurnal BP variation patterns and postural BP variation has not been investigated. We investigated the diurnal BP variation by ambulatory BP monitoring and postural BP variation during 70° head-up tilt in 110 asymptomatic hypertensive elderly subjects, who consisted of 29 subjects with white-coat hypertension and 81 with sustained hypertension with various patterns of nocturnal fall in BP (14 extreme dippers, with asleep systolic BP decrease by ≥20% of awake systolic BP; 56 dippers, with decrease by ≥0% to <20%; 11 nondippers, with decrease by <0%). During tilt, the mean (SD) systolic BP increased 10 (19) mm Hg in the extreme dippers (
P
<.02), and it decreased by 7.5 (13) mm Hg in the nondippers (
P
<.05), whereas it did not change in the dippers and white-coat hypertensive subjects. The heart rate increased in all four groups to similar degrees during tilt. Orthostatic hypertension defined as systolic BP rise of 10 mm Hg or more during tilt was found in 10 (72%) of the 14 extreme dippers, 6 (11%) of the 56 dippers, and 1 (9%) of the 11 nondippers, while orthostatic hypotension defined as systolic BP decrease of 20 mm Hg or more was found in 3 (27%), 5 (9%), and 1 (7%) of the nondippers, dippers, and extreme dippers, respectively (χ
2
=29.3,
P
<.0001). In conclusion, the abnormal diurnal BP variation is closely related to the abnormal postural BP variation in elderly hypertensive patients, with extreme dippers showing orthostatic hypertension and nondippers showing orthostatic hypotension. The upright position during the daytime, which increases the BP in the extreme dippers and decreases it in the nondippers, may in part produce abnormal diurnal BP variation.
Estrogens Increase Transcription of the Human Endothelial NO Synthase Gene
Authors: Kleinert Hartmut , Wallerath Thomas , Euchenhofer Christian , Ihrig-Biedert Irmgard , Li Huige , Förstermann Ulrich
Published: June 2012

Abstract
—Estrogens have been found to reduce the incidence of cardiovascular disease that has been ascribed in part to an increased expression and/or activity of the vasoprotective endothelial NO synthase (NOS III). Some reports have shown that the level of expression of this constitutive enzyme can be upregulated by estrogens. The current study investigates the molecular mechanism of the NOS III upregulation in human endothelial EA.hy 926 cells. Incubation of EA.hy 926 cells with 17β-estradiol or the more stable 17α-ethinyl estradiol enhanced NOS III mRNA and protein expression up to 1.8-fold, without changing the stability of the NOS III mRNA. There was no enhancement of NOS III mRNA after incubation of EA.hy 926 cells with testosterone, progesterone, or dihydrocortisol or when 17α-ethinyl estradiol was added together with the estrogen antagonist RU58668, indicating a specific estrogenic response. Nuclear run-on assays indicated that the increase in NOS III mRNA is the result of an estrogen-induced enhancement of NOS III gene transcription. In transient transfection experiments using a 1.6 kb human NOS III promoter fragment (which contains no bona fide estrogen-responsive element, ERE), basal promoter activity was enhanced 1.7-fold by 17α-ethinyl estradiol. In electrophoretic mobility shift assays, nuclear extracts from estrogen-incubated EA.hy 926 cells showed no enhanced binding activity either for the ERE-like motif in the human NOS III promoter or for transcription factor GATA. However, binding of transcription factor Sp1 (which is essential for the activity of the human NOS III promoter) was significantly enhanced by estrogens. These data suggest that the estrogen stimulation of the NOS III promoter could be mediated in part by an increased activity of transcription factor Sp1.
Vasodilation With Sodium Nitroprusside Does Not Improve Insulin Action in Essential Hypertension
Authors: Natali Andrea , Galvan Alfredo Quiñones , Pecori Neda , Sanna Giovanna , Toschi Elena , Ferrannini Ele
Published: June 2012

Abstract—
The vasodilation induced by systemic insulin infusion is mediated by nitric oxide and is impaired both in obese subjects and patients with essential hypertension. Whether this vascular defect explains the metabolic resistance to insulin action is uncertain. In 8 overweight male patients with essential hypertension, we used the double forearm (ie, infused versus control) technique, combined with the euglycemic hyperinsulinemic clamp, to test whether sustained vasodilation (induced by intra-arterial sodium nitroprusside infusion) improves insulin-mediated glucose uptake. During the clamp, whole-body glucose disposal rose to 24.4±2.9 μmol · min
−1
· kg
−1
. Forearm blood flow in the control forearm was stable (3.1±0.4 versus 2.9±0.3 mL · min
−1
· dL
−1
), while in the infused forearm it increased from 3.4±0.5 to 10.6±1.3 mL · min
−1
· dL
−1
in response to sodium nitroprusside. During insulin administration, tissue glucose extraction rose from 2±1% to 21±4% (
P
<.001) in the control forearm and from 2±1% to 8±3% in the infused forearm (
P
<.02 versus baseline for both); the calculated net glucose uptake reached similar plateaus in the two forearms (3.5±0.7 versus 3.7±0.6 μmol · min
−1
· kg
−1
, control versus infused,
P
=.6). We conclude that in overweight male patients with essential hypertension, increasing forearm perfusion with sodium nitroprusside does not attenuate the insulin resistance of forearm tissues.
Independent Genetic Susceptibility to Cardiac Hypertrophy in Inherited Hypertension
Authors: Innes Brendan A. , McLaughlin Michael G. , Kapuscinski Miroslav K. , Jacob Howard J. , Harrap Stephen B.
Published: June 2012

Abstract
—Cardiac hypertrophy is a common but not inevitable complication of hypertension. Variation in heart size in hypertensives may reflect independent genetic susceptibility to cardiac hypertrophy. Using an experimental genetic model, we determined the location of quantitative trait loci responsible for cardiac hypertrophy and/or hypertension. We studied 182 F
2
male animals derived from a cross of the spontaneously hypertensive rat and normotensive Donryu rats. Direct mean arterial pressure (MAP) and left ventricular (LV) mass were measured at 20 weeks of age, and DNA was obtained for linkage analysis. The estimated heritability of MAP was 62% and for LV mass expressed per unit of body weight (relative LV mass) was 76%. We used 185 polymorphic markers, with an average intermarker distance of 12.3 centimorgans for a genome-wide scan in a representative subgroup of 46 animals to identify preliminary quantitative trait loci, which were then mapped in all 182 male F
2
rats. Two loci showed logarithm of the odds scores of >4.0. One on chromosome 2,
Lvm-1
, was linked to relative LV mass but showed no evidence of linkage to MAP. Another locus on chromosome 1,
Map-1
, was linked to MAP. In the same region, a locus
Lvm-2
was linked with relative LV mass. These data indicate the existence of a genetic locus on chromosome 2 of the spontaneously hypertensive rat that affects relative LV mass independently of blood pressure.
Amlodipine Monotherapy, Angiotensin-Converting Enzyme Inhibition, and Combination Therapy With Pacing-Induced Heart Failure
Authors: Kribbs Scott B. , Merritt William M. , Clair Mark J. , Krombach R. Stephen , Houck Ward V. , Dodd Michael G. , Mukherjee Rupak , Spinale Francis G.
Published: June 2012

Abstract
—In patients with congestive heart failure (CHF) receiving therapy with angiotensin-converting enzyme (ACE) inhibition, institution of calcium channel antagonism with amlodipine provided favorable effects. The goal of the present study was to define potential mechanisms for these effects by measuring left ventricular function, hemodynamics, and neurohormonal system activity in a model of CHF in which amlodipine treatment had been instituted either as a monotherapy or in combination with ACE inhibition. Thirty-two pigs were instrumented to allow measurement of cardiac index, total systemic resistance index, and neurohormonal activity in the conscious state and assigned to one of four groups: (1) rapid atrial pacing (240 bpm) for 3 weeks (n=8), (2) amlodipine (1.5 mg · kg
−1
· d
−1
) and pacing (n=8), (3) ACE inhibition (fosinopril 1.0 mg/kg BID) and pacing (n=8), and (4) amlodipine and ACE inhibition (1.0 mg · kg
−1
· d
−1
and 1.0 mg/kg BID, respectively) and pacing (n=8). Measurements were obtained in the normal control state and after the completion of the treatment protocols. With rapid pacing, basal resting cardiac index was reduced compared with control values (2.7±0.2 versus 4.7±0.1 L · min
−1
· m
−2
, respectively,
P
<.05) and increased from rapid pacing–only values with either amlodipine or combination therapy (3.7±0.3 and 4.4±0.5 L · min
−1
· m
−2
, respectively,
P
<.05). Basal resting total systemic resistance index was higher in the rapid pacing–only group compared with control values (2731±263 versus 1721±53 dyne · s · cm
−5
· m
2
, respectively,
P
<.05), was reduced with either amlodipine treatment or ACE inhibition (2125±226 and 2379±222 dyne · s · cm
−5
· m
2
, respectively,
P
<.05), and was normalized with combination therapy. Plasma catecholamines, renin activity, and endothelin levels were increased threefold with rapid pacing. Amlodipine, either as a monotherapy or in combination with ACE inhibition, did not result in increased plasma catecholamines and renin activity compared with the rapid pacing–only group. Furthermore, combination therapy reduced steady state norepinephrine and normalized epinephrine levels. The results of the present study demonstrated that monotherapy with either amlodipine or ACE inhibition provides beneficial effects in this pacing model of CHF. Combined amlodipine and ACE inhibition provided greater benefit with respect to vascular resistance properties and neurohormonal system activity compared with either monotherapy.
Chronic Oral Endothelin Type A Receptor Antagonism in Experimental Heart Failure
Authors: Borgeson Daniel D. , Grantham J. Aaron , Williamson Eric E. , Luchner Andreas , Redfield Margaret M. , Opgenorth Terry J. , Burnett John C.
Published: June 2012

Abstract
—Endothelin-1 (ET-1) is a cardiovascular peptide that binds to two distinct receptors, ET
A
and ET
B
, resulting in systemic and regional vasoconstriction, alteration in sodium excretion, mitogenesis, and release of other vasoactive peptides such as atrial natriuretic peptide (ANP). A role for ET-1 has been proposed in congestive heart failure (CHF) based on the increase in circulating ET-1 in this cardiovascular disease state. The present study determined the cardiorenal and endocrine responses to chronic selective oral ET
A
antagonism in experimental CHF. Two groups of conscious dogs underwent 21 days of pacing-induced CHF. These groups included a control untreated group (n=6) and a group that received an orally active ET
A
receptor antagonist (A-127722, Abbott Pharmaceuticals, 5mg/kg PO bid, n=6). Each group was studied at baseline before the onset of CHF and after 14 and 21 days of CHF. Compared with the CHF control group, the ET
A
receptor antagonism group at 14 days of CHF showed lower mean arterial pressure and systemic vascular resistance. Similarly, ET
A
receptor antagonism markedly attenuated the increase in circulating ANP despite similar atrial pressures. At 21 days of CHF, ET
A
receptor antagonism lowered pulmonary artery pressure, pulmonary vascular resistance, and systemic vascular resistance in association with a higher cardiac output. Plasma ANP remained suppressed. Despite the lower mean arterial pressure and circulating ANP in the ET
A
receptor antagonist group, the absolute decrease in sodium excretion from baseline was less compared with the untreated CHF control group. The present investigation supports the conclusion that endogenous ET-1 participates in the systemic and pulmonary vasoconstriction, the elevation of ANP, and the sodium retention that characterize this model of experimental CHF, suggesting a potential therapeutic role for ET
A
receptor antagonism in CHF.
Antihypertensive Efficacy of Treatment Regimens Used in Veterans Administration Hypertension Clinics
Authors: Perry H. Mitchell , Bingham Stephen , Horney Anne , Rutan Gale , Sambhi Mohinder , Carmody Sharon , Collins Joseph
Published: June 2012

Abstract
—There is continuing uncertainty about whether morbidity and mortality of treated hypertensive patients depends on the drug(s) used to treat or only on the level of blood pressure achieved. This study was undertaken in a sample of special Veterans Administration hypertension clinics to determine which antihypertensive drugs were selected by the involved healthcare providers and how effective they were in achieving normotension. Hypertensive veterans (n=6100) were followed in six VA Hypertension Screening and Treatment Program clinics for 46 months beginning in May 1989. Their average age was 60.7 years; 53% lived in the Stroke Belt; 46% had target organ damage, 36% were black, 23% smoked, and 10% had diabetes mellitus. Antihypertensive regimens were divided into 12 all-inclusive categories. Blood pressures were averaged at the last study visit for all patients on a regimen. The regimens of diuretic or diuretic plus β-blocker gave the lowest average pressures (140.6/82.3 mm Hg) and calcium antagonist the highest (149.0/86.5 mm Hg). ANOVA indicated that differences between seven common regimens and also between the four single drug regimens were highly significant (
P
<.0001). This pattern of low treated pressure with the “old” agents and higher treated pressure with newer agents was reflected in the percentage of patients controlled below 140/90 mm Hg and the percentage uncontrolled above 159/94 mm Hg. Blacks and patients with target organ damage resembled the entire cohort in average treated diastolic blood pressure, but the former had lower and the latter had higher treated systolic blood pressure than the entire cohort.
Nitric Oxide Opposes Myogenic Pressure Responses Predominantly in Large Arterioles In Vivo
Authors: de Wit Cor , Jahrbeck Bernhard , Schäfer Christian , Bolz Steffen-Sebastian , Pohl Ulrich
Published: June 2012

Abstract
—A myogenic vasoconstriction may amplify the effects of circulating vasoconstrictors. In cremaster arterioles, the contribution of a myogenic component to the constriction on intravenous infusion of norepinephrine (NE) or angiotensin II (Ang II) was studied. Second, the role of endothelium-derived nitric oxide (NO) in the control of these myogenic constrictions and its site of action in the resistance vascular bed was investigated. In 30 anesthetized (pentobarbital) hamsters, the cremaster was prepared for intravital microscopy, and a pneumatic vessel occluder was placed around the aorta to vary blood pressure in the hindquarter of the animal. Intravenous infusion of NE (0.5 nmol/min) increased the systemic blood pressure by 52±2 mm Hg. Simultaneously, constrictions of up to 33±6% were observed in the small arterioles (SAs; maximal inner diameter, 36 to 65 μm). The constrictions were not significantly altered by a local adrenergic blockade but were abolished when the pressure elevation in the cremaster arterioles was blocked by partial occlusion of the abdominal aorta. Diameters in large arterioles (LAs; maximal inner diameter, 65 to 127 μm), however, did not change significantly on NE infusion. Similar responses in the arterioles were observed when the local pressure was increased stepwise from 60 to 120 mm Hg by partial opening of the aortic occluder. However, after treatment of the cremaster tissue with the inhibitor of the NO synthase,
N
G
-nitro-
l
-arginine (L-NNA, 30 μmol/L), a significant pressure-induced constriction of up to 16±3% occurred in LAs, whereas the magnitude of the constriction in SAs remained unchanged. L-NNA also abolished the increases in blood flow that were observed with increments in pressure in control animals. Similar results were obtained when Ang II was used to increase blood pressure. We conclude that a myogenic constriction of SAs contributes markedly to the overall response of cremaster arterioles to circulating vasoconstrictors. NO effectively opposes the myogenic response in LAs, thus preventing myogenic constrictions in a vascular region where constriction cannot be fully controlled by metabolic dilation. If this attenuating effect of NO on myogenic constriction also takes place in other organs, it might be a decisive mechanism in controlling changes of total peripheral vascular resistance elicited by vasoconstrictors.
Hemodilution Reduces Clinic and Ambulatory Blood Pressure in Polycythemic Patients
Authors: Bertinieri Giovanni , Parati Gianfranco , Ulian Luisa , Santucciu Cinzia , Massaro Paolo , Cosentini Roberto , Torgano Giuseppe , Morganti Alberto , Mancia Giuseppe
Published: June 2012

Abstract
—Limited information is available for humans on whether blood viscosity affects total peripheral resistance and, hence, blood pressure. Our study was aimed at assessing the effects of acute changes in blood viscosity on both clinic and 24-hour ambulatory blood pressure (BP) values. In 22 normotensive and hypertensive patients with polycythemia, clinic and 24-hour ambulatory BPs were measured before and 7 to 10 days after isovolumic hemodilution; this was performed through the withdrawal of 400 to 700 mL of blood, with concomitant infusion of an equivalent volume of saline-albumin solution. Hematocrit, plasma renin activity, plasma endothelin-1, right atrial diameter (echocardiography), and blood viscosity were measured under both conditions. Plasma renin activity and right atrial diameter were used as indirect markers of blood volume changes. Plasma endothelin-1 was used to obtain information on a vasomotor substance possibly stimulated by our intervention, which could counteract vasomotor effects. Isovolumic hemodilution reduced hematocrit from 0.53±0.05 to 0.49±0.05 (
P
<.01). Plasma renin activity, plasma endothelin-1 and right atrial diameter were unchanged. Clinic blood pressure was reduced by hemodilution (systolic, 144.3±5.4 to 136.0±3.9 mm Hg[mean±SEM]; diastolic, 87.0±2.8 to 82.1±2.6 mm Hg,
P
<.05 for both) and a reduction was observed also for 24-hour average ABP (systolic, 133.6±2.9 to 129.5±2.7 mm Hg; diastolic, 80.0±2.0 to 77.3±1.7 mm Hg,
P
<.05 for both). The reduction was consistent in hypertensive patients (n=12), whereas in normotensive patients (n=10) it was small and not significant. Both clinic and 24-hour average heart rates were unaffected by the hemodilution. Thus, in polycythemia, reduction in blood viscosity without changing blood volume causes a significant fall in both clinic and 24-hour ambulatory BPs; this is particularly true when, as can often happen, blood pressure is elevated. This emphasizes the importance this variable may have in the determination of blood pressure and the potential therapeutic value of its correction when altered.
Time-Voltage QRS Area of the 12-Lead Electrocardiogram
Authors: Okin Peter M. , Roman Mary J. , Devereux Richard B. , Pickering Thomas G. , Borer Jeffrey S. , Kligfield Paul
Published: June 2012

Abstract
—Identification of left ventricular hypertrophy (LVH) using 12-lead ECG criteria based primarily on QRS amplitudes has been limited by poor sensitivity at acceptable levels of specificity. Because the product of QRS voltage and duration, as an approximation of the time-voltage area of the QRS complex, can improve accuracy of the 12-lead ECG for LVH, we examined the diagnostic value of true time-voltage area measurements of QRS complexes from the standard 12-lead ECG. Standard 12-lead ECGs and echocardiograms were obtained in 175 control subjects without LVH and in 74 patients with regurgitant valvular heart disease and LVH defined by echocardiographic criteria (indexed LV mass >110 g/m
2
in women and >125 g/m
2
in men). Standard voltage criteria, voltage-duration products (voltage multiplied by QRS duration), and true time-voltage areas of the QRS were calculated for Sokolow-Lyon criteria (SV
1
+RV
5/6
) and the 12-lead sum of voltage criteria. Test sensitivities were compared using gender-specific partitions with matched specificity of 98% in the 175 subjects without LVH. Measurement of the time-voltage area significantly improved sensitivity for both criteria. The 76% sensitivity of the 12-lead sum area and 65% sensitivity of Sokolow-Lyon area were significantly greater than the 54% sensitivity of the approximation of QRS area provided by each voltage-duration product (
P
<.001 and
P
=.021) and than the 46% and 43% sensitivities of the respective simple voltage criteria (each
P
<.001). Comparison of receiver operating characteristic curves confirmed the superior overall performance of time-voltage area criteria compared with both voltage-duration products and simple voltage criteria. These results suggest that use of time-voltage areas can dramatically improve identification of LVH by 12-lead ECG. Further study of this approach is needed to identify optimal criteria for LVH based on the time-voltage area measurements from the 12-lead ECG.
Myocardial Contractile Efficiency and Oxygen Cost of Contractility Are Preserved During Transition From Compensated Hypertrophy to Failure in Rats With Salt-Sensitive Hypertension
Authors: Morii Isao , Kihara Yasuki , Inoko Moriaki , Sasayama Shigetake
Published: June 2012

Abstract
—In Dahl-Iwai rats, salt-sensitive hypertension causes concentric left ventricular hypertrophy (LVH) at the age of 11 weeks, which is followed by LV dilatation with global hypokinesis and pulmonary congestion, ie, LV failure (LVF), at 16 to 18 weeks of age. To address the question of whether the cardiac remodeling from LVH to LVF is associated with modulations of mechanoenergetic properties, we serially measured the LV pressure-volume area (PVA) and myocardial oxygen consumption (MV̇
o
2
) in isolated, isovolumically contracting hearts from this animal model. The end-systolic pressure-volume relationships obtained by stepwise changes of the LV volume were fit into a binominal regression model, which provided a value of LV contractility (E
es
) and a volume intercept (V
0
). A slope (the reciprocal of the LV contractile efficiency) and a PVA-independent MV̇
o
2
were determined by a regression analysis of the MV̇
o
2
-PVA relation. The procedure was repeated at different Ca
2+
concentrations in perfusate to estimate the oxygen cost of contractility (
d
MV̇
o
2
/
d
E
es
). The MV̇
o
2
was further evaluated during K
+
-induced cardiac arrest to delineate the basal metabolism, which was independent of the E-C coupling. During the transition from LVH to LVF, the E
es
was decreased by 50% (from 681 to 338 mm Hg · g · mL
−1
,
P
<.001), which was associated with a substantial increase in V
0
(from 0.002 to 0.07 mL,
P
<.01). These alterations in both the inotropic state and the ventricular shape were associated with a 45% decrease in the PVA-independent MV̇
o
2
(from 800 to 440 mL O
2
· beat
−1
· g
−1
,
P
<.01). Despite these marked changes between the two stages, both the LV contractile efficiency and the oxygen cost of contractility remained unchanged. The MV̇
o
2
during cardiac arrest also showed an equal level among the groups; hence, from LVH to LVF, the nonmechanical O
2
consumption by the E-C coupling decreased in a manner parallel to the basal contractile state. We conclude that (1) in this animal model, the heart failure transition is associated with a marked decrease in myocardial contractility and with ventricular remodeling; (2) despite these changes, the efficiency of the chemomechanical conversion is highly preserved; and consequently, (3) the total energy consumption per unit of failing myocardium is diminished along with its reduced nonmechanical energy expenditure for E-C coupling. These mechanoenergetic properties might constitute an adaptive mechanism in the energy-starved condition of chronically diseased myocardium.
Sodium Induces Hypertrophy of Cultured Myocardial Myoblasts and Vascular Smooth Muscle Cells
Authors: Gu Jian-Wei , Anand Vivek , Shek Eugene W. , Moore Michael C. , Brady Ann L. , Kelly Whitney C. , Adair Thomas H.
Published: June 2012

Abstract
—The mechanisms of sodium-induced myocardial hypertrophy and vascular hypertrophy are poorly understood. We tested the hypothesis that a high sodium concentration can directly induce cellular hypertrophy. Neonatal rat myocardial myoblasts (MMbs) and vascular smooth muscle cells (VSMCs) were cultured in a 50:50 mixture of DMEM and M199 supplemented with 10% fetal bovine serum. When the monolayers reached ≈80% confluence, normal sodium medium (146 mmol/L) was replaced with high sodium media (152 mmol/L, 160 mmol/L, and 182 mmol/L) for up to 5 days. Increasing sodium from a baseline concentration of 146 mmol/L to the higher concentrations for 5 days caused dose-related increases in cell mean diameter, cell volume, and cellular protein content in both MMbs and VSMCs. Increasing the sodium concentration by only 4% (from 146 mmol/L to 152 mmol/L) caused the following respective changes in MMbs and VSMCs: 8.5% and 8.7% increase in cell mean diameter, 27.6% and 27.0% increase in cell volume, and 55.7% and 46.7% increase in cellular protein content. The rate of protein synthesis, expressed as [
3
H]leucine incorporation, increased by 87% and 99% in MMbs after exposure to 152 mmol/L and 160 mmol/L sodium, respectively, compared with the 146-mmol/L sodium control group. Exposure of MMbs to medium with a sodium concentration of 10% above normal, ie, 160 mmol/L, caused a significant decrease (range, 26% to 44%) in the rate of protein degradation at multiple time points over a 48-hour period compared with normal sodium control cells. The increase in cellular protein content caused by 160 mmol/L sodium returned to normal within 3 days after MMbs were returned to a normal sodium medium. These findings support the hypothesis that sodium has a direct effect to induce cellular hypertrophy and may therefore be an important determinant in causing myocardial and/or vascular hypertrophy in subjects with increased sodium concentration in the extracellular fluid.
Single L-Type Calcium Channels in Smooth Muscle Cells From Resistance Arteries of Spontaneously Hypertensive Rats
Authors: Ohya Yusuke , Tsuchihashi Takuya , Kagiyama Shuntaro , Abe Isao , Fujishima Masatoshi
Published: June 2012

Abstract
—The amplitude of the whole-cell L-type Ca
2+
channel current recorded from vascular smooth muscle cells is reportedly greater in spontaneously hypertensive rats (SHR) than in Wistar-Kyoto rats (WKY). However, no study has examined properties of single Ca
2+
channels in arterial cells from these strains. To further test the hypothesis that activation of L-type Ca
2+
channels in arterial smooth muscle cells would be enhanced in SHR, we recorded single Ca
2+
channel currents in resistance mesenteric artery cells from SHR and WKY (8 to 9 weeks of age) using a cell-attached patch clamp technique. With 50 mmol/L Ba
2+
in the recording pipette, the depolarizing pulse from a holding potential of −40 mV evoked the single L-type Ca
2+
channel current. Opening of the single channels was more frequent in cells from SHR than from WKY. Single-channel conductance (20 pS) and open time (1 ms at 0 mV) did not differ in the two strains. The results suggest that an increased amplitude of the whole-cell current can be attributed to the enhanced opening of single Ca
2+
channels in the arterial smooth muscle cells from SHR compared with WKY.
Seven-Year Incidence of Hypertension in a Cohort of Middle-Aged African Americans and Whites
Authors: He Jiang , Klag Michael J. , Appel Lawrence J. , Charleston Jeanne , Whelton Paul K.
Published: June 2012

Abstract
—Many studies have suggested that African Americans have a higher prevalence of hypertension than whites. The authors conducted a prospective study of hypertension incidence from 1987-1988 to 1994-1995 in 140 African American and 237 white adults aged 30 to 54 years at baseline. The study participants were screened for participation in the Trials of Hypertension Prevention, phase 1, an 18-month lifestyle modification intervention trial aimed at lowering blood pressure, at the Baltimore Clinical Center. Baseline age, blood pressure, body mass index, and heart rate were similar in the two groups. Compared with whites, however, African Americans had a lower percentage of men, college graduates, and households with an income ≥$40 000 per year. African Americans also had lower mean urinary sodium to creatinine ratio and potassium to creatinine ratio, but a similar sodium to potassium ratio. The incidence of hypertension (blood pressure ≥160/95 mm Hg and/or taking antihypertensive medication) over 7 years of follow-up was nearly identical: 25.7% in African Americans and 25.3% in whites. Baseline age, gender, blood pressure, and heart rate were all associated with the incidence of hypertension. Even after adjustment for these covariables, the risk of hypertension was not higher in African Americans compared with whites. These results indicate that middle-aged African Americans and whites have a similar risk of developing hypertension given the same age, initial blood pressure, and body mass index at baseline.
Difference Between Clinic and Daytime Blood Pressure Is Not a Measure of the White Coat Effect
Authors: Parati Gianfranco , Ulian Luisa , Santucciu Cinzia , Omboni Stefano , Mancia Giuseppe
Published: June 2012

Abstract
—The purpose of the present study was to evaluate whether the difference between blood pressure measured in the clinic or physician’s office and the average daytime blood pressure accurately reflects the blood pressure response of the patient to the physician (“white coat effect” or “white coat hypertension”). We studied 28 hypertensive outpatients (mean age, 41.8±11.2 years; age range, 21 to 64 years) of 35 consecutive patients attending our hypertension clinic, in whom (1) continuous noninvasive finger blood pressure was recorded before and during the visit, (2) blood pressure was measured according to the Riva-Rocci-Korotkoff method (mercury sphygmomanometer) with the patient in the supine position, and (3) daytime ambulatory blood pressure was monitored with a SpaceLabs 90207 device. The peak blood pressure increase recorded directly during the visit was compared with the difference between clinic and daytime average ambulatory blood pressures. Compared with previsit values, peak increases in finger systolic and diastolic blood pressures during the visit to the clinic were 38.2±3.1 and 20.7±1.6 mm Hg, respectively (mean±SEM,
P
<.01 for both). Daytime average systolic and diastolic blood pressures were 135.5±2.5 and 89.2±1.9 mm Hg, with both lower than the corresponding clinic blood pressure values (146.6±3.6 and 94.9±2.2 mm Hg,
P
<.01). These differences, however, were <30% of the peak finger blood pressure increases during the physician’s visit, to which these increases showed no relation. Although the visit to the physician’s office was associated with tachycardia (9.0±1.6 bpm,
P
<.01), there was no difference between clinic and daytime average heart rates. These data indicate that the clinic−daytime average blood pressure difference does not reflect the alerting reaction and the pressure response elicited by the physician’s visit and thus is not a reliable measure of the white coat effect.
Insulin-Mediated Venodilation Is Impaired in Patients With High Cholesterol
Authors: Sung Bong Hee , Ching Marilou , Izzo Joseph , Dandona Paresh , Wilson Michael F.
Published: June 2012

Abstract
—Recently we have reported that insulin attenuates norepinephrine (NE)-induced vasoconstriction via a cyclic GMP–NO synthase pathway. Because hypercholesterolemia has been associated with abnormal endothelial function, we investigated whether insulin-mediated vasodilation is impaired in hypercholesterolemia. To assess vasoreactivity, NE (12.5, 25, 50, and 100 ng/min), NE (100 ng/min) combined with insulin (8, 16, 24, and 32 μU/min), and NE (100 ng/min) combined with sodium nitroprusside (0.01, 0.1, 1, 10, and 100 ng/min) were infused into dorsal hand veins. Changes in venous diameter were measured by ultrasonography, using a 7.5-MHz transducer. Twenty-two healthy, normotensive hypercholesterolemic subjects (HC; mean total cholesterol 6.93 mmol/L, HDL 1.45 mmol/L, LDL 4.81 mmol/L) and 18 age-matched normal control subjects (NC; mean total cholesterol 4.81 mmol/L, HDL 1.16 mmol/L, LDL 3.18 mmol/L) were studied. All HC had normal glucose tolerance test results. Baseline vein diameters were similar between groups, and the vasoconstrictor response to NE was not significantly different between HC and NC. Insulin significantly attenuated NE-induced vasoconstriction in NC but not in HC (
P
<0.01). Both groups were able to venodilate with sodium nitroprusside. To investigate the effects of cholesterol reduction on vascular reactivity, venoreactivity studies were repeated in 12 HC after treatment with 20 to 40 mg/d lovastatin for 6 weeks. There were no significant venoreactivity changes with the treatment. Plasma LDL cholesterol concentration was inversely correlated to venodilator effect of insulin (
r
=−0.42,
P
<0.02). In conclusion, insulin-mediated vasodilation is impaired in patients with high cholesterol. Absence of normal insulin-mediated but not sodium nitroprusside–induced venodilation in hypercholesterolemia suggests that insulin-mediated vasodilation is endothelium dependent.
Red Blood Cell Sodium-Lithium Countertransport and Risk of Future Hypertension
Authors: Strazzullo Pasquale , Siani Alfonso , Cappuccio Francesco P. , Trevisan Maurizio , Ragone Eliana , Russo Luigina , Iacone Roberto , Farinaro Eduardo
Published: June 2012

Abstract
—An elevated red blood cell (RBC) sodium-lithium countertransport (Na-Li CT) is associated with high blood pressure (BP) in cross-sectional investigations; however, its value as a predictor of future hypertension, and thus of cardiovascular risk, has not been defined. The present study evaluated the association between Na-Li CT and risk of future hypertension in a sample of 106 untreated normotensive middle-aged men participating in the Olivetti Prospective Heart Study in southern Italy. BP, anthropometric and metabolic variables, and RBC Na-Li CT were measured at baseline in 1987 and at a follow-up visit in 1994 through 1995. Na-Li CT was stable over time (
r
=0.85) and was significantly associated to systolic BP in both visits. Of the 106 initially normotensive participants, 14 were found to be hypertensive at the 8-year follow-up examination. Eleven of these 14 hypertensives were in the highest tertile of systolic BP at baseline, and 9 of 11 also had an elevated baseline Na-Li CT. In multiple logistic regression analysis, baseline BP, Na-Li CT, and age were all significant predictors of the risk of future hypertension. Individuals with baseline systolic BP in the highest tertile had a 60% risk of developing hypertension if their Na-Li CT was also high, whereas their risk was only 5% if Na-Li CT was in the two lowest tertiles (
P
=0.003). RBC Na-Li CT was a valuable predictor of subsequent hypertension in middle-aged men with a high-normal BP level for their age.
Suppression of ANP Gene Transcription by Liganded Vitamin D Receptor
Authors: Chen Songcang , Wu Jianming , Hsieh Jui-Cheng , Whitfield G. Kerr , Jurutka Peter W. , Haussler Mark R. , Gardner David G.
Published: June 2012

Abstract
—We showed previously that liganded vitamin D receptor (VDR) effects a suppression of human atrial natriuretic peptide (hANP) gene-promoter activity in cultured neonatal rat atrial myocytes. In the present study, we have attempted to identify the structural domains of the VDR that are involved in mediating this suppression. We examined the effects of a series of VDR mutants on a cotransfected hANP promoter-driven chloramphenicol acetyltransferase (CAT) reporter. Neither the native VDR nor any of the mutants tested displayed inhibitory activity in the absence of the 1,25-dihydroxyvitamin D
3
(VD
3
) ligand. Δ134, a deletant harboring solely the DNA binding region of the VDR, and L254G, a mutant shown to be defective in retinoid X receptor (RXR) heterodimer formation in other systems, were as effective as the native VDR in reducing promoter activity. HBD, a deletant containing only the hormone-binding domain of the VDR, and K246G, a point mutant that is defective in the activation function of the receptor, did not attenuate reporter activity. A similar activity profile was displayed when a positively regulated promoter containing a direct-repeat vitamin D responsive element (DR3-CAT) was examined in these cells. Liganded VDR, the Δ134 mutant, and liganded L254G effected increases in DR3-CAT activity of 2.5-, 2-, and 4-fold, respectively. Two nonhypercalcemic analogues of VD
3
(RO 23–7553 and RO 25–6760) displayed the same inhibitory activity as VD
3
. These studies suggest that the inhibition of hANP promoter activity requires both the DNA binding and activation functions of the receptor but does not appear to require formation of a classic RXRα-VDR heterodimer.
Uncoupling of the Baroreflex by N
N
-Cholinergic Blockade in Dissecting the Components of Cardiovascular Regulation
Authors: Shannon John R. , Jordan Jens , Black Bonnie K. , Costa Fernando , Robertson David
Published: June 2012

Abstract
—Systemic administration of adrenergic agonists and nitric oxide donors is used extensively to determine cardiovascular receptor sensitivity. Conclusions regarding receptor sensitivity in the presence of the baroreflex may be misleading. In 8 normal volunteers, we determined the heart rate and blood pressure changes after incremental bolus doses of isoproterenol, phenylephrine, and sodium nitroprusside before and during neuronal nicotinic cholinergic (N
N
-cholinergic) blockade with trimethaphan. Results are given as median (25th/75th percentile). With trimethaphan, the baroreflex slope (as determined by bolus doses of nitroprusside and phenylephrine) decreased from 24 (22/26) to 0.00 (0.00/0.09) ms/mm Hg (
P
<0.01). The dose of isoproterenol that decreased systolic blood pressure (SBP) 12.5 mm Hg changed from 0.61 (0.51/5.3) to 0.17 (0.12/0.21) μg (
P
<0.01); the dose required to increase heart rate 12.5 bpm changed from 0.22 (0.17/0.41) to 0.74 (0.33/2.3) μg (
P
<0.01). The dose of nitroprusside required to decrease SBP 12.5 mm Hg changed from 2.3 (1.3/3.4) to 0.18 (0.14/0.24) μg/kg (
P
<0.01). The dose of phenylephrine required to increase SBP 12.5 mm Hg changed from 135 (110/200) to 16 (10/30) μg (
P
<0.01). We conclude that the efferent arc of the baroreflex can be completely interrupted with N
N
-cholinergic blockade. Estimation of adrenoreceptor sensitivity and sensitivity to nitric oxide donors by systemic administration of agonists is severely confounded by baroreflexes. Uncoupling of the baroreflex by N
N
-cholinergic blockade may be a useful method to obtain an integrated measure of adrenergic receptor sensitivity and sensitivity to nitric oxide donors in humans. This approach would permit the comparison of normal and abnormal physiological states without the “noise” of baroreflex buffering.
Insulin Resistance in Hypertension Is Associated With Body Fat Rather Than Blood Pressure
Authors: Toft Ingrid , Bønaa Kaare H. , Jenssen Trond
Published: June 2012

Abstract
—The insulin resistance syndrome has been characterized by hypertension, upper body obesity, insulin resistance, hyperinsulinemia, glucose intolerance, and hypertriglyceridemia. Previous studies are inconsistent regarding the relationship between blood pressure and insulin resistance. We therefore compared the metabolic profile in 60 hypertensive subjects (mean±SD arterial pressure, 116±7 mm Hg) and 60 normotensive subjects (mean arterial pressure, 88±5 mm Hg) matched for age, gender, and body mass index. Hypertensives had significantly higher waist-to-hip ratio than normotensives (
P
=0.002). The groups did not differ in fasting plasma glucose (0.2 mmol/L,
P
=0.09), insulin (6 pmol/L,
P
=0.14), insulin sensitivity index (−0.01 μmol · kg
−1
· min
−1
· pmol/L
−1
,
P
=0.7), and suppression of nonesterified fatty acids during a hyperglycemic clamp (1%,
P
=0.40). There were significant differences in fasting levels of C-peptide (50 pmol/L,
P
=0.004) and proinsulin (2 pmol/L,
P
=0.01), 2-hour postload levels of glucose (0.8 mmol/L,
P
=0.01) and insulin (84 pmol/L,
P
=0.01) after oral glucose challenge, and hepatic glucose production during the clamp (2.87 μmol · kg
−1
· min
−1
,
P
=0.02). These differences were not significant when controlling for waist-to-hip ratio. Body mass index and waist-to-hip ratio were similarly associated with the insulin sensitivity index in the hypertensive (
r
=−0.59,
P
=0.0001 and
r
=−0.32,
P
=0.05) and normotensive (
r
=−0.58,
P
=0.0001 and
r
=−0.39,
P
=0.05) groups. Hypertension per se is not associated with insulin resistance. However, even small increments in both body mass index and waist-to-hip ratio, as often seen in hypertension, may lead to impairment in insulin sensitivity, probably mediated through altered lipid metabolism.