bluuebunny/crossref_metadata_2025 huggingface dataset:
Vasodilators, Aortic Elasticity, and Ventricular End-Systolic Stress in Nonanesthetized, Unrestrained Rats
Authors: Niederhoffer Nathalie , Marque Valérie , Lartaud-Idjouadiene Isabelle , Duvivier Claude , Peslin René , Atkinson Jeffrey
Published: June 2012

Abstract
We evaluated the effect of different vasodilators on ventricular end-systolic stress by investigating the impact of sodium nitroprusside, nifedipine, and hydralazine on blood pressure, aortic stiffness, and wave reflection during drug-induced hypotension (to 80 mm Hg mean blood pressure) in normotensive (central aortic mean blood pressure, 116 to 119 mm Hg; systolic pressure, 133 to 137 mm Hg), nonanesthetized, unrestrained rats. Aortic stiffness was evaluated from the slope of the linear regression relating pulse wave velocity (PWV) to central aortic mean or pulse pressure. The fall in central aortic systolic blood pressure was less than the fall in mean pressure, especially after hydralazine (122±4 mm Hg; sodium nitroprusside, 107±2; and nifedipine, 112±3 mm Hg;
P
<.05). The PWV/mean pressure slope was linear, positive, and similar in all three groups (hydralazine, 3.3±0.2; sodium nitroprusside, 3.8±0.3; and nifedipine, 3.9±0.3 cm · s
−1
· mm Hg
−1
;
P
>.05). The PWV/pulse pressure slope was linear, negative, and less steep in the case of hydralazine (−4.9±0.6; sodium nitroprusside, −15.5±3.7; and nifedipine, −13.5±2.9 cm · s
−1
· mm Hg
−1
;
P
<.05). The travel time and augmentation index of the reflected wave were similar in all groups. In conclusion, sodium nitroprusside and nifedipine had a more beneficial effect on end-systolic stress than did hydralazine. This does not appear to be related to any specific effect on wave reflection or the “static” relationship between PWV and aortic mean blood pressure; it may be related to the effects of these drugs on the “dynamic” relationship between PWV and pulse pressure.
Interactions Between Nitric Oxide and Angiotensin II on Renal Cortical and Papillary Blood Flow
Authors: Madrid María Isabel , García-Salom Miguel , Tornel Jerónimo , de Gasparo Marc , Fenoy Francisco J.
Published: June 2012

Abstract
This study examined the role of angiotensin II (Ang II) on the effects of nitric oxide (NO) synthesis blockade on renal cortical and papillary blood flow in innervated and denervated kidneys of volume-expanded Munich-Wistar rats with hormonal influences on the kidney that were held constant by intravenous infusion. Cortical (CBF) and papillary (PBF) blood flow were measured by laser-Doppler flowmetry. A low dose of
N
ω
-nitro-
l
-arginine methyl ester (
L
-NAME, 3.7 nmol · kg
−1
· min
−1
) reduced CBF only in innervated kidneys, and this effect was abolished by subsequent administration of valsartan (an AT
1
antagonist). L-NAME 3.7 nmol · kg
−1
· min
−1
improved PBF autoregulation by lowering PBF to the range of 100 to 140 mm Hg of perfusion pressure, and this effect was attenuated or abolished by valsartan in innervated and denervated kidneys, respectively. These results indicate that the cortical and medullary vasoconstriction induced by a low dose of L-NAME are caused by potentiation of the vasoconstrictor influence of renal sympathetic nerves and Ang II. A higher dose of L-NAME (37 nmol · kg
−1
· min
−1
) lowered CBF and PBF in both innervated and denervated kidneys. This effect of L-NAME on the cortical circulation was abolished by valsartan, but this AT
1
antagonist had no effect on the medullary vasoconstriction produced by NO synthesis blockade. Therefore, a higher dose of L-NAME induces a renal cortical vasoconstriction through potentiation of the renin-angiotensin system, whereas the fall of PBF seen after L-NAME 37 nmol · kg
−1
· min
−1
seems to be caused primarily by NO suppression. This Ang II potentiation produced by L-NAME in the renal cortex seems to be mediated by AT
1
receptors, because it was unaffected by
PD123319
(an AT
2
antagonist). The results of the present study indicate that NO is an important modulator of the vasoconstrictor influence of Ang II in the renal cortical circulation of the rat. However, although there are some interactions between NO and renal nerves and Ang II on the medullary circulation, the renal medullary vasoconstriction produced by L-NAME appears to be caused primarily by NO suppression, with little influence of the renal vasoconstrictor systems.
Sensitivity of Blood Pressure and Renin Activation During Sodium Restriction
Authors: Krekels Marielle M. E. , Schaper Nicolaas C. , de Leeuw Peter W.
Published: June 2012

Abstract
The objective of the present study was to explore the interrelationships among cumulative sodium loss, renin activation, and blood pressure changes during sodium restriction in essential hypertensive patients. Specifically, we wanted to know whether the degree of sodium sensitivity of blood pressure depends on renin activation during steady state or on initial renin activation during the first days of sodium restriction. Sixty-seven untreated essential hypertensive patients were admitted to a metabolic ward for 8 days and put on a sodium restricted diet of 55 mmol/d from the second to the last day. Urinary excretions of sodium, potassium, and creatinine were determined along with mean arterial pressure and weight during 7 days. Besides measurements in steady state condition (after 7 days), active plasma renin concentration, aldosterone, and catecholamines were also assessed during the first 3 days of sodium restriction. Analyzable data are available for 55 patients. Baseline sodium excretion and the activation of renin during the first 3 days both appeared to be predictors of total sodium loss after 7 days. Changes in blood pressure were not related to changes in sodium balance, but they were to baseline blood pressure, baseline norepinephrine, and renin activation during the early phase of sodium restriction. In addition, blood pressure appeared to fall more when the normal relationship between sodium loss and early (but not late) activation of renin was disturbed. We conclude that sodium sensitivity of blood pressure during sodium restriction is associated with a relative unresponsiveness of the renin system during the early phase of sodium loss rather than to absolute renin levels during steady state.
Perindopril Ameliorates Glomerular and Renal Tubulointerstitial Injury in the SHR/N-Corpulent Rat
Authors: Velasquez Manuel T. , Striffler John S. , Abraham Andrew A. , Michaelis Otho E. , Scalbert Elizabeth , Thibault Nancy
Published: June 2012

Abstract
We compared the effects of long-term treatment with the angiotensin-converting enzyme inhibitor perindopril and triple therapy (hydrochlorothiazide, reserpine, and hydralazine) on the metabolic and renal features in the SHR/N-corpulent (cp) rat, a genetic model of non–insulin-dependent diabetes mellitus and hypertension. Obese male SHR/N-cp rats (4 to 6 weeks old) were fed a 54% carbohydrate diet containing 18% sucrose and 36% starch. After 2 months on the diet, rats were assigned to one of three groups: one group (n=8) received perindopril (PE); the second group (n=8) received triple therapy (TT); and the third group (n=8) did not receive therapy. Treatment was maintained for 3 to 4 months. Body weight, food intake, and fasting levels of serum glucose and insulin did not differ among the three groups. Control rats exhibited progressive proteinuria in parallel with the rise in systolic blood pressure (SBP). Both PE and TT equally lowered SBP to normal levels and reduced proteinuria in treated rats. However, the reduction of proteinuria was greater and more sustained with PE than with TT (
P
<.05), whereas the effect of TT on proteinuria was delayed. Plasma renin activity was increased in PE and TT rats compared with control rats (
P
<.02). Semiquantitative analysis of renal lesions showed that the percentage of glomeruli with mesangial expansion and sclerosis and the tubulointerstitial score (an index of severity of tubulointerstitial lesions, namely tubular atrophy, inflammatory cellular infiltrates, and interstitial fibrosis) was reduced in both PE and TT rats. However, the reduction of glomerulosclerosis and tubulointerstitial lesions was greater in PE than in TT rats (
P
<.01). The percentage of glomerular sclerosis was positively correlated with the severity score of tubulointerstitial lesions (
r
=.60,
P
<.01). We conclude that PE is more effective than TT in halting the progression of proteinuria in the SHR/N-cp rat with non–insulin-dependent diabetes mellitus and hypertension. The antiproteinuric effect of PE is associated with significant reduction in glomerulosclerosis and tubulointerstitial lesions, independent of the effect of treating hypertension.
Expression of the Subtype 2 Angiotensin (AT
2
) Receptor Protein in Rat Kidney
Authors: Ozono Ryoji , Wang Zhi-Qin , Moore Allan F. , Inagami Tadashi , Siragy Helmy M. , Carey Robert M.
Published: June 2012

Abstract
In situ hybridization studies have suggested that the subtype 2 angiotensin (AT
2
) receptor gene is expressed in fetal and newborn rat kidney but is undetectable in the adult animals. In the present study, we investigated the expression of AT
2
receptor protein in the fetal (days 14 and 19 of fetal life), newborn (day 1 postpartum), and adult (4-week-old and 3-month-old) rat kidney. Polyclonal anti-peptide antiserum was raised against the amino terminus of the native AT
2
receptor. The selectivity of the antiserum was validated by recognition of the AT
2
receptor in a stably transfected COS-7 cell line by Western blot and immunocytochemical analysis. As a positive control, the AT
2
receptor signal was detected strongly in the adrenal gland. Positive immunohistochemical staining was observed in the mesenchymal cells and ureteric buds of the 14-day fetal kidney and in the glomeruli, tubules, and vessels in the 19-day fetal and newborn kidney. Glomeruli expressing the AT
2
receptor were localized mainly in the outer layer of the renal cortex. In the young (4-week-old) and mature (3-month-old) adult rat on normal sodium intake, renal AT
2
receptor immunoreactivity was present in glomeruli but substantially diminished compared with that of newborn rats. In both young and mature adult rats, dietary sodium depletion increased the renal AT
2
receptor signal, mainly in the glomeruli and interstitial cells. Preimmune and preadsorption controls were negative. Western blot analysis detected a single 44-kD band in the fetal and newborn rat kidney and in the young and mature adult rat kidney. Dietary sodium depletion increased the density of the AT
2
receptor band in mature adult rat kidneys. These data provide evidence that the AT
2
receptor protein is expressed in the fetal and newborn rat kidney, diminishes in adult life, and is reexpressed in the adult in response to sodium depletion.
Cardiac Type-1 Angiotensin II Receptor Status in Deoxycorticosterone Acetate–Salt Hypertension in Rats
Authors: Fareh Jeannette , Touyz Rhian M. , Schiffrin Ernesto L. , Thibault Gaetan
Published: June 2012

Abstract
The regulation of angiotensin II (Ang II) receptors and Ang II–induced modulation of intracellular Ca
2+
concentration in cardiac cells from hearts of experimentally induced hypertensive deoxycorticosterone acetate (DOCA)–salt and control unilaterally nephrectomized (Uni-Nx) Sprague-Dawley rats was assessed. Ang II receptor density and intracellular Ca
2+
concentration measurements were examined in adult ventricular myocytes and fibroblasts by radioligand binding assay and digital imaging using fura 2 methodology, respectively. Four-week DOCA-salt treatment induced hypertension associated with cardiac hypertrophy. Ang II binding studies demonstrated that adult ventricular myocytes and fibroblasts possess mainly the AT
1
subtype receptor. Moreover, DOCA-salt hypertension was associated with a 1.8-fold increase in Ang II–specific binding compared with myocytes from Uni-Nx control rats. Intracellular Ca
2+
responses induced by increasing Ang II concentrations (10
−12
to 10
−4
mol/L) were significantly enhanced in cardiomyocytes from DOCA-salt rats. The effects of Ang II on intracellular Ca
2+
spike frequency were unaltered in cardiomyocytes from DOCA-salt–hypertensive rats. The density of AT
1
subtype receptors was not modified in ventricular fibroblasts after DOCA-salt treatment. Ang II increased intracellular Ca
2+
concentration similarly in ventricular fibroblasts from normal and hypertensive rats. In conclusion, DOCA-salt hypertension is characterized by an increased AT
1
receptor density and intracellular calcium responses in ventricular myocytes, whereas in ventricular fibroblasts the AT
1
receptor status is unaltered. These findings report for the first time the cardiac cell–specific implication of Ang II and the intracellular calcium signaling pathway stimulated by the AT
1
receptor in cardiac hypertrophy in DOCA-salt–hypertensive rats.
Susceptibility to Pain in Hypertensive and Normotensive Patients With Coronary Artery Disease
Authors: Falcone Colomba , Auguadro Carla , Sconocchia Renato , Angoli Luigi
Published: June 2012

Abstract
An association between a decreased responsiveness to varying painful stimuli and arterial hypertension both in animals and in humans has been documented. The relationship between essential hypertension and silent myocardial ischemia in coronary artery disease (CAD) populations is not well understood. The aims of this study in CAD patients with and without essential hypertension were (1) to determine dental pain threshold and reaction to tooth pulp stimulation and (2) to ascertain whether hypertensive CAD patients differ from normotensive ones in reactivity to pain. This study involved 182 patients who were affected by mild and moderate hypertension (G1) and 174 normotensive patients (G2). The inclusion criteria were reproducible exercise-induced myocardial ischemia, CAD documented at angiography, and dental formula suitable for pulp test. All patients underwent an ergometric stress test, coronary angiography, and pulp test. Our CAD hypertensive patients showed a lower prevalence of angina during daily life (64.8% in G1 versus 81.6% in G2,
P
<.05) and a higher incidence of exercise-induced silent myocardial ischemia (60.4% in G1 versus 48.8% in G2,
P
<.05) than the normotensive group. The mean anginal pain intensity, which was suffered both during spontaneous transitory episodes of ischemia and/or during acute myocardial infarction, was significantly lower in G1 than in G2 patients (
P
<.05). During pulp test, 31.8% of G1 and 13.7% of G2 referred no symptoms, even at the highest current intensity of 500 mA. The hypertensive patients with symptoms during pulp test had a higher mean dental pain threshold and lower mean threshold reaction and maximal reaction than did the normotensive symptomatic ones. In patients of both groups, a positive correlation between the mean maximal reaction during pulp test and the prevalence of angina during daily life was also found. In conclusion, patients with CAD and essential hypertension differ from normotensive CAD patients in reactivity to pain. Significantly higher pain thresholds and lower reactions to tooth pulp stimulation characterized patients with increased blood pressure values.
Increased Expression of Parathyroid Hormone–Related Peptide Gene in Blood Vessels of Spontaneously Hypertensive Rats
Authors: Noda Masakuni , Katoh Tetsuo , Kurokawa Kiyoshi , Takuwa Yoh
Published: June 2012

Abstract
We have shown recently that mechanical stretch of cultured rat aortic smooth muscle cells induces a marked increase in gene expression of the vasorelaxant parathyroid hormone–related peptide. In the present study, we investigated whether mechanical force affected the in vivo parathyroid hormone–related peptide gene expression in blood vessels. Northern blot analysis revealed that stretch of isolated rat aortic strips increased the expression level of parathyroid hormone–related peptide mRNA. The parathyroid hormone–related peptide transcript level in aorta and mesenteric vessels from 18-week-old spontaneously hypertensive rats (SHR) was 2.5- and 2.2-fold higher, respectively, compared with age-matched Wistar-Kyoto (WKY) controls, whereas the parathyroid hormone–related peptide mRNA level in aorta from normotensive 4-week-old SHR was similar to that of age-matched WKY controls. The aortic parathyroid hormone–related peptide content was higher in 18-week-old SHR than in age-matched WKY controls. Moreover, treatment of mature SHR with an angiotensin II type 1 receptor antagonist or hydralazine caused a concomitant decrease in the parathyroid hormone–related peptide transcript level in aorta with lowering of blood pressure. These results suggest that the in vivo parathyroid hormone–related peptide gene expression in blood vessels is under the control of mechanical force, pointing to a role of parathyroid hormone–related peptide in the regulation of vascular tone.
Membrane Ion Transport in Bartter’s Syndrome
Authors: Koren Wladimir , Peleg Edna , Rosenthal Talma , Postnov Yuvenaly V.
Published: June 2012

Abstract
Fifteen patients with Bartter’s syndrome (hyponatremic hypochloremic hypokalemic metabolic alkalosis) were compared with 15 healthy volunteers. Red blood cell Na
+
/H
+
and Cl
−
/HCO
3
−
exchanges were enhanced in all patients with Bartter’s syndrome. In calciuric normomagnesemic patients, sensitive to nonsteroidal anti-inflammatory drugs (classic Bartter’s syndrome), red blood cell Na
+
,K
+
,2Cl
−
cotransport was markedly reduced, calcium-dependent K
+
permeability was moderately increased, and up to 60% of sodium permeability was represented by cAMP-activated fraction (presumably human analog of β-isoform of Na
+
/H
+
exchange). In noncalciuric hypomagnesemic patients insensitive to indomethacin (Gitelman’s syndrome), Na
+
,K
+
,2Cl
−
cotransport was enhanced, Na
+
permeability was increased due to calmodulin-dependent fraction, and calcium-dependent K
+
permeability was markedly enhanced. A new subtype of Bartter-like syndrome (“variant Bartter’s syndrome”) has been described in which calciuria, hypomagnesemia, and insensitivity to nonsteroidal anti-inflammatory drugs were associated with decreased Na
+
,K
+
,2Cl
−
cotransport, enhanced calmodulin-activated fraction of Na
+
influx, and reduced calcium-dependent K
+
permeability.
Role of Endothelin in Hypertension of Experimental Chronic Renal Failure
Authors: Potter Gregg S. , Johnson Ron J. , Fink Gregory D.
Published: June 2012

Abstract
Surgical ablation of renal mass leads to a reduction in kidney function and commonly to the development of hypertension and chronic renal failure (CRF) in rats. The objective of this study was to determine whether endothelin (ET)-1 is involved in the maintenance of the hypertension that accompanies loss of renal mass. First, we demonstrated the antihypertensive efficacy of PD 155080, a selective, orally active ET
A
receptor antagonist, in a group of rats made hypertensive by continuous intravenous infusion of ET-1 (2.5 pmol · kg
−1
· min
−1
) for 7 days. ET-1 produced a sustained hypertension and PD 155080 (56.4 μmol/kg [25mg/kg] BID PO) normalized blood pressure (BP) during the 5 days of drug administration. In a second experiment, Sprague-Dawley rats underwent a 5/6 reduction in renal mass (RRM); 4 weeks later, PD 155080 administered for 7 days resulted in a sustained reduction in BP. Sham-operated rats also showed a slight hypotensive response to PD 155080 administration. Plasma urea nitrogen, plasma creatinine, urinary protein excretion, and creatinine clearance were not altered by PD 155080 administration in RRM or sham rats. In a third experiment, we investigated the contribution of the renin-angiotensin system to BP control in RRM rats given PD 155080. In these rats, PD 155080 reduced BP during 5 treatment days, and this antihypertensive effect was not altered by coadministration of the angiotensin-converting enzyme inhibitor enalapril in the drinking water (508 μmol/L [250 mg/L]). These results demonstrate that (1) ET-1 plays a role in established RRM hypertension through activation of the ET
A
receptor subtype, (2) lowering blood pressure with PD 155080 in RRM rats does not adversely affect renal function, and 3) the antihypertensive effect of ET
A
receptor antagonism is not opposed by the renin-angiotensin system.
Bosentan Prevents Preglomerular Alterations During Angiotensin II Hypertension
Authors: Casellas Daniel , Bouriquet Nathalie , Herizi Abderraouf
Published: June 2012

Abstract
The present study was performed to characterize structurofunctional alterations of preglomerular vessels during chronic angiotensin II (Ang II)–induced hypertension (Ang II group: 400 ng · kg
−1
· min
−1
, 10 days) and to assess the role of endothelin-1 in rats receiving Ang II and the mixed receptor antagonist bosentan (Ang II+B group: 30 mg · kg
−1
· d
−1
, 10 days). Systolic blood pressure rose by 56±3 and 54±6 mm Hg in Ang II and Ang II+B rats, respectively. Albuminuria increased similarly in both Ang II–treated groups, reflecting glomerular barrier dysfunction. Preglomerular vessels were isolated after HCl maceration and comprised arcuate arteries and their branches, interlobular arteries (ILA), and afferent arterioles (AA). In the Ang II group, focal vascular lesions affected 36±6%, 20±5%, and 4±1% of arcuate arterial branches, ILA, and AA, respectively. They were characterized by 74% increased media thickness and accumulation of Sudan black–positive (SB
+
) lipid droplets, and media cell proliferation was documented through immunohistochemistry. The occurrence of SB
+
lesions was strikingly reduced with bosentan. Autoregulatory responses (AR) were assessed along ILA and AA with the use of blood-perfused juxtamedullary nephron preparations. AR were elicited by raising blood perfusion pressure from 60 to 160 mm Hg and quantified through videomicroscopy as pressure-induced constrictions. AR were inhibited in Ang II–treated rats along ILA and AA; Ang II–induced AR changes were prevented by bosentan. Maximal relaxation induced by Mn
2+
revealed equal basal tone in Ang II–treated, Ang II+B–treated, and control vessels. Chronic Ang II–induced hypertension is therefore associated with the development of SB
+
lesions and selective impairment of AR in juxtamedullary nephrons. Endothelin-1 likely mediates the structurofunctional alterations of preglomerular vasculature during Ang II hypertension.
Birth Weight Versus Childhood Growth as Determinants of Adult Blood Pressure
Authors: Falkner Bonita , Hulman Sonia , Kushner Harvey
Published: June 2012

Abstract—
In older white American adults, recent retrospective studies have demonstrated a relationship between lower birth weight and hypertension. Black Americans have a higher occurrence of both lower birth weight and hypertension than do white Americans. To test the low birth weight–high blood pressure hypothesis, data from a prospective study (Perinatal Collaborative Project) were examined. The study followed a sample of 137 black Americans, with nine examinations. Data on birth weight, growth, and blood pressure from birth through 28.0±2.7 years were obtained longitudinally. Bivariate correlations among parameters were computed with the Pearson
r
. Birth weight and blood pressure at age 28 years are not correlated (Pearson
r
=.06). However, systolic blood pressures measured at 0.3 years and thereafter are correlated with adult systolic blood pressure. Also, weight at 0.3 years and body mass index at 7 years and thereafter are correlated with adult weight. Our data did not confirm the birth weight–blood pressure hypothesis. Rather, we detected significant correlations between preadult measurements of blood pressure and weight with adult measurements. These results indicate that in black Americans, childhood growth is a stronger determinant than intrauterine growth of adult blood pressure.
Role of Endogenous Nitric Oxide in the Brain Stem on the Rapid AdaptatKion of Baroreflex
Authors: Hironaga Kiyoshi , Hirooka Yoshitaka , Matsuo Isamu , Shihara Miwako , Tagawa Tatsuya , Harasawa Yasuhiko , Takeshita Akira
Published: June 2012

Abstract
—It has been shown that nitric oxide in the brain stem plays an important role in the control of sympathetic nerve activity. We examined the role of endogenous nitric oxide in the brain stem in the rapid central adaptation of baroreflex control of sympathetic nerve activity in anesthetized rabbits. Bilateral carotid sinuses were isolated, and a stepwise increase in pressure of 25 or 50 mm Hg for 50 to 60 seconds was applied to the carotid sinuses while the arterial pressure and renal sympathetic nerve activity were recorded. The renal sympathetic nerve activity was inhibited by the stepwise increase in carotid sinus pressure, but thereafter it gradually returned toward the baseline level despite the fact that carotid sinus pressure was kept constant. This procedure was performed after intracisternal injection of
N
ω
-nitro-
l
-arginine methyl ester (L-NAME, 8 μmol),
N
ω
-nitro-
d
-arginine methyl ester (D-NAME, 8 μmol),
l
-arginine (40 μmol), or the vehicle solution. The magnitude of the immediate and maximal inhibition of renal sympathetic nerve activity caused by a stepwise increase in carotid sinus pressure was similar between the vehicle and L-NAME treatment, but the rate of recovery of the renal sympathetic nerve activity after immediate inhibition was faster after L-NAME than after vehicle.
l
-Arginine reversed the effects of L-NAME. However, D-NAME or
l
-arginine alone had no such effects on the rate of recovery of the nerve activity. These results thus suggest that endogenous nitric oxide in the brain stem attenuates rapid adaptation of the arterial baroreflex control of the sympathetic nerve activity in rabbits.
Effect of Renin Gene Transfer on Blood Pressure in the Spontaneously Hypertensive Rat
Authors: St. Lezin Elizabeth , Liu Weizhong , Wang Ning , Wang Jia-Ming , Kren Vladimir , Zidek Vaclav , Zdobinska Miroslava , Krenova Drahomira , Bottger Anita , van Zutphen Bert F. M. , Pravenec Michal
Published: June 2012

To investigate whether molecular variation in the renin gene contributes to the greater blood pressure of spontaneously hypertensive rats (SHR) versus normotensive Brown Norway (BN) rats, we measured blood pressure in an SHR progenitor strain and an SHR congenic strain that are genetically identical except at the renin gene and an associated segment of chromosome 13 transferred from the BN strain. Backcross breeding and molecular selection at the renin locus were used to create the SHR congenic strain (designated SHR.BN-
Ren
) that carries the renin gene transferred from the normotensive BN strain. We found that transfer of the renin gene from the BN strain onto the genetic background of the SHR did not decrease blood pressure in rats fed either a normal or high-salt diet. In fact, the systolic blood pressures of the SHR congenic rats tended to be slightly greater than the systolic blood pressures of the SHR progenitor rats. However, the congenic strain exhibited lower serum high-density lipoprotein cholesterol, and greater levels of total cholesterol, very-low-density lipoprotein, and intermediate-density lipoprotein cholesterol during administration of a high-fat, high-cholesterol diet. These findings demonstrate that (1) under the environmental circumstances of the current study, the greater blood pressure of SHR versus BN rats cannot be explained by strain differences in the renin gene and (2) a quantitative trait locus affecting lipid metabolism exists on chromosome 13 within the transferred chromosome segment. The SHR.BN-
Ren
congenic strain may provide a useful new animal model for studying the interaction between high blood pressure and dyslipidemia in cardiovascular disease.
Calcium Mobilization Contributes to Pressure-Mediated Afferent Arteriolar Vasoconstriction
Authors: Inscho Edward W. , Cook Anthony K. , Mui Vy , Imig John D.
Published: June 2012

Preglomerular responses to vasoactive agonists utilize calcium released from intracellular stores and activation of calcium influx pathways to elicit vasoconstriction. The current study was performed to determine the role of calcium release from intracellular stores on the afferent arteriolar response to increases in perfusion pressure. Experiments were performed, in vitro, using the blood perfused, juxtamedullary nephron technique combined with videomicroscopy. The response of afferent arterioles to 30 mm Hg increases in perfusion pressure was determined before and after depletion of intracellular calcium pools with a 10-minute preincubation with 1 μmol/L thapsigargin or 100 μmol/L cyclopiazonic acid. Afferent arteriolar diameter averaged 20.2±1.0 μm (n = 19) at a control perfusion pressure of 100 mm Hg. Increasing perfusion pressure to 130 and 160 mm Hg reduced afferent caliber by 10.7±1.0% (
P
<.05 versus con) and by 24.7±1.6% (
P
<.05 versus diameter at 130 mm Hg); respectively. Thapsigargin significantly increased afferent diameter by 21±2% (n = 6) at 100 mm Hg and prevented pressure-induced autoregulatory responses. Afferent diameter averaged 24.3±1.7, 24.5±1.8 and 24.3±1.8μm at perfusion pressures of 100, 130 and 160 mm Hg; respectively. Cyclopiazonic acid treatment also inhibited autoregulatory behavior but did not alter resting vessel diameter. Afferent arteriolar diameter (n = 6) averaged 21.4±1.9μm at 100 mm Hg and 20.9±2.1 and 20.5±2.2μm at 130 and 160 mm Hg; respectively. Additional studies were performed to assess the role of phospholipase C activity in pressure-mediated autoregulatory behavior of afferent arterioles. Step increases in perfusion pressure decreased afferent diameter by 10.7±3.8 and 21.7±4.1%; respectively. Administration of the phospholipase C inhibitor, U-73122, (5 μmoles/L) did not significantly alter baseline diameter but did attenuate the pressure-mediated vasoconstrictor response. Increasing perfusion pressure to 130 and 160 mm Hg reduced afferent diameter by only 6.5±1.5 and 10.0±2.0%; respectively. These data demonstrate that interruption of calcium mobilization with thapsigargin, cyclopiazonic acid, or phospholipase C inhibition markedly attenuates pressure-mediated afferent arteriolar vasoconstriction and suggests that autoregulatory adjustments in afferent arteriolar diameter involve calcium release from inositoltrisphosphate (IP
3
)-sensitive intracellular stores.
Increased Cardiac Angiotensin II Receptors in Angiotensinogen-Deficient Mice
Authors: Sumida Yoichi , Umemura Satoshi , Tamura Kouichi , Kihara Minoru , Kobayashi Shun-ichi , Ishigami Tomoaki , Yabana Machiko , Nyui Nobuo , Ochiai Hisao , Fukamizu Akiyoshi , Miyazaki Hitoshi , Murakami Kazuo , Ishii Masao
Published: June 2012

Abstract
—Two subtypes of angiotensin II (Ang II) receptors, type 1 (AT
1
-R) and type 2 (AT
2
-R), have been identified in the heart. However, little is known about the regulation of cardiac AT
1
-R and AT
2
-R by Ang II in vivo. Thus, we examined cardiac AT
1
-R and AT
2
-R in angiotensinogen-deficient (
Atg-/-
) mice that are hypotensive and lack circulating Ang II. Cardiac Ang II receptors (Ang II-R) were assessed by radioligand binding with
125
I-[Sar
1
,Ile
8
]–Ang II in plasma membrane fractions. AT
1
-R and AT
2
-R were distinguished using their specific antagonists CV-11974 and
PD123319
, respectively. Total densities of Ang II-R and AT
1
-R density were significantly greater in the
Atg-/-
mice than
Atg+/+
mice (31.1±2.8 versus18.8±2.1, 28.7±3.0 versus16.9±2.3 fmol/mg protein,
P
<.01, respectively), and AT
2
-R showed a slight but not significant increase in
Atg-/-
mice relative to
Atg+/+
control animals.
K
d
values were not different between the two groups. In contrast to binding experiments, levels of Ang II type 1a receptor (AT
1a
-R) and AT
2
-R mRNA did not differ between
Atg-/-
and
Atg+/+
mice. These results suggest that lack of Ang II may upregulate AT
1
-R through translational and/or posttranslational mechanisms in
Atg-/-
mice.
NK1 Receptor Antagonist Blocks Angiotensin II Responses in Renin Transgenic Rat Medulla Oblongata
Authors: Diz Debra I. , Westwood Brian , Bosch Susan M. , Ganten Detlev , Ferrario Carlos
Published: June 2012

Anginotensin (Ang) II increases substance P (SP) efflux from perfused slices of medulla oblongata, and a peptide antagonist of SP, [Leu

11

,ψCH
2
NH10-11]SP, blocks the acute hypotension and bradycardia caused by Ang II injected into the nucleus tractus solitarii (nTS) of Harlan Sprague-Dawley (SD) rats. We investigated whether the same relationships exist in (mRen2)27 renin transgenic (TG) rats, which have chronic elevations of medullary tissue Ang II levels. Ang II increased SP efflux (48% above control;
P
<0.01) from slices of medulla prepared from 8-to 12-week old male TG rats. Injections of Ang II (250 fmol in 30 nL) into the nTS of chloralose-urethane anesthetized TG rats produced a significant increase in pressure of 7±2 mm Hg before a 13±3 mm Hg fall in pressure. Ang II induced similar depressor responses in Hannover SD rats but no increase in pressure. After nTS injection of the NK1-selective SP antagonist CP-96,345 (30 pmol in 60 nL), Ang II-induced hypotension was blocked in both groups, as was the pressor component in hypertensive rats. Hypotensive and bradycaric effects of glutamate (0.6 nmol in 30 nL) injected into the nTS were not altered by CP-96,345. In vitro receptor autoradiography showed that the SP antagonist (10 or 100 μM) did not compete from
125
I-Ang II binding in the dorsal medulla, a result suggesting that it did not interact directly with Ang II receptors. Thus, the nTS cardiovascular effects of Ang II are mediated by SP in both normotensive rats and a model of hypertension with altered endogenous levels of Ang II. These findings link Ang II-induced effects on SP release from brain slices of the medulla oblongata to acute cardiovascular actions of the peptide through an NK1 receptor.
Carotid Wall Viscosity Increase Is Related to Intima-Media Thickening in Hypertensive Patients
Authors: Armentano Ricardo L. , Graf Sebastián , Barra Juan G. , Velikovsky Gerardo , Baglivo Hugo , Sánchez Ramiro , Simon Alain , Pichel Ricardo H. , Levenson Jaime
Published: June 2012

Increases in arterial wall viscosity and intima-media thickness (IMT) were found in hypertensive patients. Because smooth muscle cells are responsible for the viscous behavior of the arterial wall and they are involved in the process of thickening of the intima-media complex, this study evaluates the relationship between carotid thickness and wall viscosity. The simultaneous and noninvasive assessment of the intima-media complex and arterial diameter waveform was performed using high-resolution ultrasonography. This technique was contrasted against sonomicrometry in sheep, showing that the waveforms obtained by both methods were similar. The common carotid arteries of 11 normotensive subjects (NTA) and 11 patients with mild to moderate essential hypertension (HTA) were measured noninvasively by using tonometry and an automatic densitometric analysis of B-mode images to obtain IMT and instantaneous pressure and diameter loops. A viscoelastic model was used to derive the wall viscosity index (η) using the hysteresis loop elimination criteria. In NTA, η was 2.73±1.66 (mm Hg · s/mm) and IMT was 0.58±0.08 (mm), whereas in HTA, η was 5.91±2.34 (
P
<.025) and IMT was 0.70±0.12 (
P
<.025), respectively. When all data of η versus IMT of NTA and HTA were pooled in a linear regression analysis, a correlation coefficient of
r
=.71 (
P
<.05) was obtained. Partial correlation between η and IMT holding constant pressure was
r
=.59 (
P
<.05). In conclusion, wall viscosity increase was associated with a higher IMT even maintaining blood pressure fixed, suggesting that the intima-media thickening might be related to smooth muscle alterations manifested as an increase in viscous behavior.
Chlamydia pneumoniae
Antibodies in Severe Essential Hypertension
Authors: Cook P. J. , Lip G. Y. H. , Davies P. , Beevers D. G. , Wise R. , Honeybourne D.
Published: June 2012

Abstract
—Several studies have implied an association between
Chlamydia pneumoniae (C. pneumoniae)
and cardiovascular disease. Our study was designed to determine whether this organism is associated with severe essential hypertension in a multiracial British population. Antibodies to
C. pneumoniae
were measured by microimmunofluorescence in 123 patients with chronic severe hypertension and 123 control subjects, matched for ethnic origin, age, sex, and smoking habit, admitted to the same hospital with various noncardiovascular, nonpulmonary disorders. Previous infection was defined by IgG 64 to 256, provided that there was no detectable IgM. Multiple regression analyses of matched and unmatched data were used to investigate the influences of antibody levels and potential confounding factors (ethnic origin, age, sex, smoking habit, diabetes mellitus, and social deprivation) on hypertension. A portion of the hypertensive patients underwent echocardiography, estimation of left ventricular mass index, and measurements of fibrinogen, D-dimer, and von Willebrand factor concentrations. Thirty-five percent of hypertensive patients and 17.9% of matched control subjects had antibody titers consistent with previous
C. pneumoniae
infection. The hypertensive patients differed significantly from their matched control subjects in their level of previous infection, with an odds ratio of 2.5 (95% confidence interval, 1.3 to 4.7). There were no significant differences in antibody levels between patients with left ventricular hypertrophy and those without it. Fibrinogen, D-dimer, and von Willebrand factor concentrations were not significantly associated with antibody levels. These data support an association of
C. pneumoniae
with severe essential hypertension. They provide no evidence of a predisposition to develop left ventricular hypertrophy in hypertensive patients with
C. pneumoniae
infection or of associations with hypercoagulability or endothelial dysfunction.
Low-Density Lipoprotein Oxidation and Vitamins E and C in Sustained and White-Coat Hypertension
Authors: Pierdomenico Sante D. , Costantini Fabrizio , Bucci Anna , De Cesare Domenico , Cuccurullo Franco , Mezzetti Andrea
Published: June 2012

Abstract
—Low-density lipoprotein oxidation and antioxidant vitamins E and C were investigated in white-coat hypertension in comparison with sustained hypertension and normotension. We selected 21 sustained hypertensive subjects, 21 white-coat hypertensive subjects, and 21 normotensive subjects matched for gender, age, and body mass index. White-coat hypertension was defined as clinical hypertension and daytime ambulatory blood pressure <139/90 (subjects were also reclassified using 134/90 and 135/85 mm Hg as cutoff points for daytime blood pressure). Blood samples were drawn for lipid profile determination, assessment of fluorescent products of lipid peroxidation in native LDL, evaluation of susceptibility to LDL oxidation in vitro (lag phase and propagation rate), and determination of LDL vitamin E and plasma vitamins E and C contents. Compared with sustained hypertensive subjects, white-coat hypertensives had significantly lower fluorescent products of lipid peroxidation (15.4±3.4 versus 10.2±3 units of relative fluorescence/mg LDL protein,
P
<.05), longer lag phase (54±10 versus 88±10 minutes,
P
<.05), lower propagation rate (8.2±2.5 versus 5.95±2.1 nmol diene/min per mg LDL cholesterol,
P
<.05), higher LDL vitamin E content (8.3±1.1 versus 10.1±1.8 nmol/mg LDL cholesterol,
P
<.05), and plasma vitamin C content (40±13 versus 57±9 μmol/L,
P
<. 05). No significant difference was observed between white-coat hypertensive and normotensive subjects. The results did not change after reclassification of subjects. Our data show that white-coat hypertensive subjects do not show an enhanced propensity to LDL oxidation or reduction in antioxidant vitamins. Given the role of LDL oxidation in the development of atherosclerosis and that of vitamin E and C in protecting against it, these findings suggest that white-coat hypertension per se carries a low atherogenic risk.
Persistent Reduction in Renal Nerve Growth Factor mRNA After Perindopril Treatment of Young Spontaneously Hypertensive Rats
Authors: Charchar Fadi J. , Kapuscinski Miroslav , Harrap Stephen B.
Published: June 2012

Abstract
—Nerve growth factor (NGF) determines sympathetic innervation of target tissues, and NGF levels are increased in young spontaneously hypertensive rats (SHR). Angiotensin can affect NGF levels, and the persistent reduction in blood pressure after brief angiotensin-converting enzyme inhibition in young SHR may involve long-term changes in NGF and sympathetic innervation. We measured the relative abundance of renal NGF mRNA by reverse transcription–polymerase chain reaction in SHR during and after treatment from 6 to 10 weeks of age with vehicle, perindopril (3 mg/kg per day), the bradykinin B
2
antagonist Hoe 140 (0.5 mg/kg per day), both perindopril and Hoe 140, or angiotensin II (Ang II; 200 ng/kg per minute). Glomerular filtration rates were estimated at 10 and 20 weeks of age. At 10 weeks of age, Ang II caused a significant (
P
<.01) increase and perindopril caused a significant (
P
<.01) decrease in renal NGF mRNA levels. Blockade of the bradykinin B
2
receptor during perindopril treatment attenuated (
P
<.05) the reduction in NGF mRNA levels. Renal NGF mRNA (
P
=.005) and blood pressure (
P
<.001) remained significantly lower than control 10 weeks after perindopril treatment was stopped. The partial reduction in blood pressure at 20 weeks of age in rats that had received perindopril and Hoe 140 was not associated with any difference in renal NGF mRNA. Perindopril-induced long-term reduction in renal NGF mRNA levels may decrease sympathetic innervation and thereby contribute to the long-term posttreatment blood pressure reduction.
Electroneutral Na-Coupled Cotransporter Expression in the Kidney During Variations of NaCl and Water Metabolism
Authors: Moreno Gabriela , Merino Alejandra , Mercado Adriana , Herrera Juan Pablo , González-Salazar Jorge , Correa-Rotter Ricardo , Hebert Steven C. , Gamba Gerardo
Published: June 2012

Abstract
—The purpose of the present study was to analyze the long-term regulation of renal bumetanide-sensitive Na
+
-K
+
-2Cl
−
cotransporter and thiazide-sensitive Na
+
-Cl
−
cotransporter gene expression during changes in NaCl and water metabolism. Male Wistar rats exposed to high or low NaCl intake, saline loading, dehydration, water loading, and furosemide administration during 7 days were studied. Control groups had access to regular food and tap water. Rats were kept in metabolic cages for 4 days before and during the experiment to determine daily urinary electrolyte excretion and osmolarity. At the end of the experiment, creatinine clearance and serum electrolyte levels were also measured. Kidneys were excised and macroscopically subdivided into cortex and outer and inner medulla. Total RNA was extracted from each individual cortex or outer medulla by use of the guanidine/cesium chloride method. The Na
+
-K
+
-2Cl
−
cotransporter expression in outer medulla total RNA was assessed by nonradioactive Northern blot analysis and the Na
+
-Cl
−
cotransporter expression in renal cortex total RNA was assessed by semiquantitative polymerase chain reaction. Experimental maneuvers were adequately tolerated, and all groups developed the appropriate renal response to each challenge. However, the level of expression of both cotransporters did not change in any model, except for a 2.8-fold increase in the Na
+
-Cl
−
cotransporter expression during dehydration. We conclude that nephron adaptation to 7-day modifications in NaCl and water metabolism does not include changes in the amount of electroneutral sodium-coupled cotransporter gene expression at the mRNA level.
Hypertension Optimal Treatment (HOT) Study
Authors: Kjeldsen Sverre E. , Hedner Thomas , Jamerson Kenneth , Julius Stevo , Haley William E. , Zabalgoitia Miguel , Butt Amir R. , Rahman S. Noor , Hansson Lennart
Published: June 2012

Abstract
—The Hypertension Optimal Treatment Study is a prospective trial conducted in 26 countries. The aims are to (1) evaluate the relationship between three levels of target office diastolic blood pressure (BP) (≤80, ≤85, or ≤90 mm Hg) and cardiovascular morbidity and mortality in hypertensive patients and (2) examine the effects on cardiovascular morbidity and mortality of 75 mg aspirin daily versus placebo. A total of 19 193 patients between 50 and 80 years of age had been randomized by the end of April 1994. Treatment was initiated with felodipine 5 mg daily, and additional therapy was given in accordance with a set protocol. The present substudy of 926 patients performed in nine countries aimed to (1) compare home with office BP in a representative subsample of the HOT population after the titration of treatment was completed and (2) clarify whether the separation into the target groups could be expanded into the out-of-office setting. The differences between office and home measurements in diastolic BP of 0.2 mm Hg (SD, 9; 95% confidence interval, −0.36 to 0.81;
P
=.40) and systolic BP of 0.5 mm Hg (SD, 15; 95% confidence interval, −0.53 to 1.46;
P
=.21) were not significant. The group differences in home BP were 1.9 mm Hg (≤80 versus ≤85) and 1.2 mm Hg (≤85 versus ≤90) for diastolic BP (F=11.69; ANOVA,
P
<.0001) and 2.6 and 2.1 mm Hg for systolic BP (F=8.44,
P
=.0002). Thus, office and home BPs measured with the same semiautomatic device are comparable in treated hypertensive subjects in the HOT Study, and the separation into the target groups based on office readings prevails at home.
Enhanced Depressor Response to Nitric Oxide in the Rostral Ventrolateral Medulla of Spontaneously Hypertensive Rats
Authors: Kagiyama Shuntaro , Tsuchihashi Takuya , Abe Isao , Fujishima Masatoshi
Published: June 2012

Abstract
—Possible impairment of the
l
-arginine–nitric oxide (NO) pathway in the rostral ventrolateral medulla of adult spontaneously hypertensive rats (SHR) was investigated by microinjecting
N
G
-nitro-
l
-arginine methyl ester (L-NAME), NOC 18 (an NO donor), or
l
-arginine. Unilateral injection of L-NAME (10 nmol/50 nL) into the rostral ventrolateral medulla significantly increased mean arterial pressure (MAP) in both SHR and Wistar-Kyoto rats (WKY). The increases in MAP did not differ significantly between the two strains (15±3 versus 10±2 mm Hg, respectively; n=8). In contrast, microinjection of
l-
arginine elicited significant (
P
<.05) dose-dependent decreases in MAP in both strains, and these depressor responses were significantly greater in SHR than in WKY (in 10 nmol of
l-
arginine: –29±2 versus –15±2 mm Hg, respectively; n=8,
P
<.01). Similarly, microinjection of NOC 18 (10 nmol/50 nL) reduced MAP in both strains, and the depressor response was also significantly greater in SHR than in WKY (–38±7 versus –22±3 mm Hg, respectively; n=8,
P
<.05). These results suggest that the
l
-arginine–NO pathway in the rostral ventrolateral medulla is impaired in SHR and that this impairment may contribute to the increase in arterial pressure in this animal model of genetic hypertension.