bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Amlodipine on Glomerular Filtration, Growth, and Injury in Experimental Hypertension
Authors: Dworkin Lance D. , Tolbert Evelyn , Recht Phoebe A. , Hersch Jonathan C. , Feiner Helen , Levin Richard I.
Published: June 2012

Abstract
The objective of this study was to determine whether the calcium antagonist amlodipine could slow the progression of chronic renal disease. We examined the effects of amlodipine on kidney structure and function in two experimental models of hypertension. In the first study, adult, male Munich Wistar rats underwent uninephrectomy and were given weekly injections of desoxycorticosterone and 1% saline for drinking. Rats ingested normal chow or chow containing amlodipine for 8 weeks. The drug reduced systemic blood pressure, but glomerular filtration rate, kidney weight, proteinuria, and morphological evidence of glomerular injury were not affected. In the second study, male spontaneously hypertensive rats underwent uninephrectomy at 5 weeks of age and were followed for 6 months, during which they received no therapy or amlodipine. The drug dose was determined in preliminary studies to be the highest dose not associated with marked growth retardation. Again, although systemic blood pressure was significantly reduced by amlodipine, proteinuria and the prevalence of glomerulosclerosis were similar in amlodipine-treated and control spontaneously hypertensive rats. Micropuncture studies revealed that glomerular pressure remained elevated in amlodipine-treated spontaneously hypertensive rats. Kidney weight and glomerular volume were also similar in amlodipine-treated and control rats. Amlodipine also failed to inhibit platelet aggregation. Therefore, antihypertensive therapy with amlodipine fails to reduce glomerular pressure in spontaneously hypertensive rats as well as glomerular size and injury in spontaneously hypertension rats and desoxycorticosterone-salt hypertension. Although other dihydropyridine calcium antagonists have been found to reduce experimental glomerular injury, these data suggest that amlodipine may not prevent hypertensive nephrosclerosis.
Comparison of Changes in Cardiac Structure After Treatment in Secondary Hypertension
Authors: Yoshitomi Yuji , Nishikimi Toshio , Abe Hitoshi , Yoshiwara Fumiki , Suzuki Toshihide , Ashizawa Atsushi , Nagata Seiki , Kuramochi Morio , Matsuoka Hiroaki , Omae Teruo
Published: June 2012

Abstract
To investigate the role of aldosterone and the renin-angiotensin system in cardiac structure, we performed echocardiography in patients with secondary hypertension. The relation between blood pressure or hormonal influences and left ventricular hypertrophy has not been well established in secondary hypertension. Sixteen patients with primary aldosteronism and 11 with unilateral renovascular hypertension who had completely normalized blood pressure after operation or percutaneous transluminal angioplasty were evaluated by echocardiography before and after surgery or other interventional treatment. Blood pressure was not statistically different between the groups before treatment and was normalized after treatment in both groups. Left ventricular hypertrophy was mild in both groups before treatment, and its degree was not statistically different between the groups. At the end of the follow-up period, all parameters of primary aldosteronism and left ventricular mass index in patients with unilateral renovascular hypertension were significantly reduced. In patients with primary aldosteronism, changes in end-diastolic left ventricular internal dimension correlated positively with changes in left ventricular mass index (
r
=.58,
P
<.01). In patients with unilateral renovascular hypertension, changes in mean blood pressure and left ventricular mass index were significantly correlated (
r
=.77,
P
<.01). The expanded plasma volume induced by an excess of aldosterone and high blood pressure may play an important role in the increase of left ventricular mass in primary aldosteronism. In unilateral renovascular hypertension, high blood pressure mainly contributes significantly to increased left ventricular mass. Therefore, different factors may modulate the development of left ventricular hypertrophy in patients with secondary hypertension.
Effect of 1 Year of Lisinopril Treatment on Cardiac Autonomic Control in Hypertensive Patients With Left Ventricular Hypertrophy
Authors: Petretta Mario , Bonaduce Domenico , Marciano Fortunato , Bianchi Valter , Valva Giuseppe , Apicella Claudio , de Luca Nicola , Gisonni Pietro
Published: June 2012

Abstract
In this study we evaluated in hypertensive patients the effects of drug-induced left ventricular hypertrophy regression on cardiac autonomic control, as assessed by means of heart period variability analysis. Power spectral analysis of 24-hour electrocardiographic monitoring was performed in 30 hypertensive patients with left ventricular hypertrophy at baseline, after 1 year of lisinopril treatment, and after 1 month of drug withdrawal. At the same times, patients underwent 24-hour blood pressure monitoring, echocardiographic study, and plasma renin activity assessment. Lisinopril treatment increased plasma renin activity and reduced 24-hour systolic and diastolic pressures (from 159±14 to 121±8 and from 103±7 to 80±3 mm Hg, respectively) and left ventricular mass index (from 159±33 to 134±26 g/m
2
); moreover, in 12 of 30 patients, left ventricular mass normalization was achieved. Drug withdrawal was followed by an increase in blood pressure without left ventricular mass modification. In the total study population, only high-frequency power was higher after lisinopril treatment. In the subgroup of patients with left ventricular mass normalization, daytime and nighttime high-frequency powers as well as nighttime total and very-low-frequency powers were higher after 1 year of treatment than at baseline. In the remaining 18 patients, power spectral measures after treatment were slightly lower than at baseline and were even lower after drug withdrawal. Thus, in hypertensive hypertrophic patients, lisinopril treatment improves sympathovagal imbalance when left ventricular mass normalization is achieved. In patients without left ventricular mass normalization, drug withdrawal is followed by a worsening of neural cardiac control.
Parathyroid Hormone–Related Protein Inhibits Endothelin-1 Production
Authors: Jiang Bingbing , Morimoto Shigeto , Fukuo Keisuke , Hirotani Atsushi , Tamatani Michio , Nakahashi Takeshi , Nishibe Akira , Niinobu Tadaaki , Hata Shigeki , Chen Shaoyan , Ogihara Toshio
Published: June 2012

Abstract
The effect of human parathyroid hormone–related protein, a powerful vasodilator, on endothelin-1 production in cultured bovine pulmonary arterial endothelial cells was studied. Treatment with parathyroid hormone–related protein(1-34) at concentrations of 10
−9
to 10
−6
mol/L for 24 hours caused dose-dependent suppression of the secretion of endothelin-1, with maximal suppression at 10
−7
mol/L to 74% of the control value. This inhibitory effect was completely abolished by coincubation with 100 ng/mL pertussis toxin, an inhibitor of GTP binding protein. Furthermore, addition of
N
G
-monomethyl-
l
-arginine, an inhibitor of nitric oxide synthase, at 10
−3
mol/L significantly blocked the suppressive effect of parathyroid hormone–related protein(1-34) on endothelin-1 secretion, and further addition of 5×10
−3
mol/L
l
-arginine significantly attenuated the blocking effect of
N
G
-monomethyl-
l
-arginine. Parathyroid hormone–related protein(1-34) at 10
−7
mol/L resulted in an approximately fivefold increase in intracellular cGMP level. Northern blot analysis revealed that parathyroid hormone–related protein(1-34) inhibited both basal and thrombin-induced endothelin-1 gene expression. These findings suggest that the vasodilating property of parathyroid hormone–related protein may be mediated in part through its inhibitory effect on endothelin-1 production, which is probably mediated through nitric oxide and cGMP in endothelial cells. Thus, a feedback regulatory mechanism may exist between parathyroid hormone–related protein and endothelin-1 in the vascular wall.
Platelet Activation in Carotid Sinuses Triggers Reflex Sympathoinhibition and Hypotension
Authors: Mao Hui Z. , Li Zhi , Chapleau Mark W.
Published: June 2012

Abstract
The carotid sinuses, one of the major sites of baroreceptor innervation, are also a common site of atherosclerotic lesions and platelet aggregation. The goal of the present study was to determine whether platelet activation in carotid sinuses causes reflex-mediated changes in renal sympathetic nerve activity and arterial pressure. Rabbit platelets were isolated, resuspended in Krebs’ buffer, and activated by thrombin. Injection of activated platelets (3×10
8
platelets/mL) into the vascularly isolated carotid sinuses of anesthetized rabbits essentially eliminated sympathetic nerve activity and acutely decreased mean arterial pressure from 126±5 to 53±4 mm Hg (n=16;
P
<.05). Sympathetic activity and arterial pressure returned to control levels over a period of minutes despite sustained exposure to activated platelets. Injection of U-46619, a thromboxane analogue and vasoconstrictor, into carotid sinuses did not alter sympathetic activity or arterial pressure. However, serotonin (5-hydroxytryptamine [5-HT]), which is known to be released from activated platelets, and the 5-HT
3
receptor agonist phenylbiguanide mimicked the effect of platelets. Furthermore, the platelet-induced reflex inhibition of sympathetic activity and hypotension were not altered by the cyclooxygenase inhibitor indomethacin but were attenuated significantly by 5-HT receptor antagonists. Platelet activation inhibited sympathetic activity to 5±2% of control in the absence of antagonists but to only 35±11 and 76±4% of control after selective blockade of 5-HT
2
and 5-HT
3
receptors with ketanserin and MDL-72222, respectively. The results indicate that (1) platelet activation in carotid sinuses triggers reflex inhibition of sympathetic nerve activity and hypotension; (2) the reflex is not caused by carotid vasoconstriction and is not mediated by prostanoids; and (3) the reflex is mediated by 5-HT acting primarily on 5-HT
3
and to a lesser extent on 5-HT
2
receptors. We speculate that this reflex may contribute to arterial pressure lability and susceptibility to stroke in patients with carotid atherosclerotic disease.
Acute Sympathoinhibitory Actions of Metformin in Spontaneously Hypertensive Rats
Authors: Petersen Jørgen S. , DiBona Gerald F.
Published: June 2012

Abstract
Chronic treatment with the antihyperglycemic agent metformin prevents hypertension in spontaneously hypertensive rats. This effect has been ascribed to normalization of plasma insulin levels. However, whether metformin affects arterial pressure via changes in sympathetic nerve activity is unknown. Therefore, the objective of this study was to examine whether acute administration of metformin produces changes in mean arterial pressure, heart rate, or efferent renal sympathetic nerve activity in spontaneously hypertensive rats. Rats were anesthetized with alphaxalone-alphadolone (Saffan), paralyzed with pancuronium, and artificially ventilated. Intravenous administration of metformin (0, 1, 10, 100 mg/kg) produced dose-dependent reversible decreases in mean arterial pressure, heart rate, and efferent renal sympathetic nerve activity that were not affected by arterial or cardiopulmonary baroreceptor denervation, nitric oxide synthase inhibition by
N
ω
-nitro-
l
-arginine methyl ester, or cyclooxygenase inhibition by indomethacin. Metformin given into the lateral cerebral ventricle (250, 500, 1000 μg) produced dose-dependent decreases in mean arterial pressure, heart rate, and efferent renal sympathetic nerve activity in doses that caused no changes when given intravenously. The sympathoinhibitory response to intracerebroventricular administration of metformin was not affected by α
2
-adrenoceptor blockade by intracerebroventricular yohimbine. We conclude that metformin has acute sympathoinhibitory effects (decreased arterial pressure, heart rate, and efferent renal sympathetic nerve activity) that are produced by a direct central nervous system site of action.
Role of 20-HETE in Elevating Loop Chloride Reabsorption in Dahl SS/Jr Rats
Authors: Zou Ai-Ping , Drummond Heather A. , Roman Richard J.
Published: June 2012

Abstract
In vivo tubular perfusion experiments were performed in normotensive Dahl salt-sensitive (SS/Jr) and salt-resistant (SR/Jr) rats maintained from birth on a low salt (0.4% NaCl) diet to examine the role of 20-HETE in elevating loop Cl
−
transport in SS/Jr rats. Chloride reabsorption in the loop of Henle was significantly greater in SS/Jr than in SR/Jr rats (77±2% versus 57±3% of the perfused Cl
−
load). When the renal metabolism of arachidonic acid by P450 was blocked by the addition of 17-octadecynoic acid (10 μmol/L) to the perfusate, loop Cl
−
transport increased in SR/Jr rats to 70±2% of the delivered Cl
−
load, but it had no effect in SS/Jr rats. Conversely, addition of 20-HETE (10 μmol/L) to the perfusate lowered loop Cl
−
transport in S rats to 60±2% of perfused Cl
−
load, but it had no effect in SR/Jr rats. Addition of another endogenously formed HETE to the perfusate, 15-HETE (20 μmol/L), had no effect on Cl
−
reabsorption in the loop of Henle of SS/Jr rats. These findings indicate that endogenously produced P450 metabolites of arachidonic acid regulate Cl
−
transport in the loop of Henle of the rat in vivo and support the view that a diminished production of 20-HETE in the outer medulla of SS/Jr rats contributes to the elevation in loop Cl
−
transport and the resetting of the pressure-natriuresis relation in these animals.
Renal Response to
l
-Arginine in Salt-Sensitive Patients With Essential Hypertension
Authors: Higashi Yukihito , Oshima Tetsuya , Watanabe Mitsuaki , Matsuura Hideo , Kajiyama Goro
Published: June 2012

Abstract
This study examined whether disturbances in nitric oxide formation contribute to renal dysfunction in salt-sensitive essential hypertensive patients. We evaluated the effects of intravenous administration of
l
-arginine (500 mg/kg given over 30 minutes) on systemic and renal hemodynamics in 23 patients with mild essential hypertension during 1 week of a low NaCl diet (50 mmol/d) followed by 1 week of a high NaCl diet (340 mmol/d). Patients were classified as salt sensitive (n=10) or salt resistant (n=13) based on salt-induced changes in their blood pressures. Salt loading increased renal vascular resistance but not renal plasma flow in salt-sensitive patients. The
l
-arginine–induced renovascular relaxation was significantly reduced by a high NaCl diet (renal vascular resistance: low NaCl −12.4±2.3% versus high NaCl −7.1±1.8%,
P
<.001) in salt-sensitive patients, whereas it was unchanged in salt-resistant patients. The increase in plasma cGMP in response to
l
-arginine was also reduced by a high NaCl diet in the salt-sensitive patients (low NaCl 49±7% versus high NaCl 36±8%,
P
<.05) but not in the salt-resistant patients (low NaCl 51±6 versus high NaCl 58±6%). These findings suggest that NaCl loading in salt-sensitive patients with mild essential hypertension reduces the ability of
l
-arginine to produce nitric oxide in the endothelium of the renal vasculature.
Mechanisms of Action of Atrial Natriuretic Factor and C-Type Natriuretic Peptide
Authors: Amin Janki , Carretero Oscar A. , Ito Sadayoshi
Published: June 2012

Abstract
After secretion by the heart, atrial natriuretic factor (ANF) circulates in plasma, whereas C-type natriuretic peptide (CNP), which is found in abundance in the endothelium, may regulate vascular tone in a paracrine manner. However, there is little information on the effect of CNP on renal microvessels. We hypothesized that CNP dilates the afferent arteriole via the nitric oxide pathway, whereas ANF acts directly on vascular smooth muscle cells. When we perfused rat kidneys with minimal essential medium and bovine serum albumin at 100 mm Hg and examined the juxtamedullary afferent arterioles, neither CNP nor ANF was found to have any effect. When the peptides were added to arterioles preconstricted with norepinephrine, CNP and ANF dilated them in a similar fashion; diameters increased by 25±4% (n=7) and 29±6% (n=6) at 10
−7
mol/L, respectively (
P
<.008). Pretreatment with 10
−4
mol/L
N
-nitro-
l
-arginine methyl ester (L-NAME) or 5×10
−6
mol/L indomethacin blocked CNP-induced dilation; dilation by ANF was unaffected by indomethacin (52±25%, n=5) and potentiated by L
-
NAME (73±14%, n=5). Thus, CNP dilates the afferent arterioles via the prostaglandin/nitric oxide pathway, whereas ANF dilates them directly. This difference may be important in controlling glomerular hemodynamics.
Obesity Hypertension Is Related More to Insulin’s Fatty Acid Than Glucose Action
Authors: Egan Brent M. , Hennes Magda M.I. , Stepniakowski Konrad T. , O’Shaughnessy Irene M. , Kissebah Ahmed H. , Goodfriend Theodore L.
Published: June 2012

Abstract
Although resistance to insulin-mediated glucose disposal has emerged as a link between abdominal obesity and hypertension, abnormalities of nonesterified fatty acid metabolism may play a greater role. Analyses were performed on existing data from 17 abdominally obese subjects (11 hypertensive, 6 normotensive) to determine whether fatty acid concentration and turnover were related to blood pressure independently of hyperinsulinemia and resistance to insulin-mediated glucose disposal. Glucose utilization, fatty acid concentration, and fatty acid turnover were obtained fasting and during euglycemic hyperinsulinemia at 10 and 40 mU·m
−2
·min
−1
. Analyses were also performed on another group of 30 subjects with a wide range of risk factors who had blood pressure data as well as glucose and fatty acid measurements during an insulin tolerance test.

Fatty acid concentration and turnover were markedly more resistant to suppression by insulin in obese hypertensive than in lean or obese normotensive individuals. In the 17 obese subjects, blood pressure measured at screening, in the laboratory, and over a period of 24 hours correlated significantly with fatty acid concentration and turnover but not with glucose disposal measured during the hyperinsulinemic clamp. These correlations remained significant after fasting insulin, the insulin area under the curve during an oral glucose tolerance test, and glucose disposal during the clamp were controlled for. In the second group of subjects, plasma fatty acids 15 minutes after intravenous insulin also correlated with blood pressure. These correlations remained significant after insulin and an index of sensitivity to insulin-mediated glucose disposal were statistically controlled for. The data indicate that blood pressure is related to the effects of insulin on fatty acid metabolism. The findings raise the possibility that resistance of hormone-sensitive lipase to insulin participates in elevating the blood pressure of abdominally obese hypertensive subjects by increasing fatty acid concentration and turnover.
Regulation of Na
+
,K
+
-ATPase α-Subunit Expression by Mechanical Strain in Aortic Smooth Muscle Cells
Authors: Songu-Mize Emel , Liu Xiang , Stones Janet E. , Hymel Lin J.
Published: June 2012

Abstract
We have previously demonstrated that vascular sodium pump activity is stimulated in several rat models of hypertension. In addition, others have reported an upregulation of mRNA for the Na
+
,K
+
-ATPase α
1
-subunit in hypertension. To test the effect of sustained, cyclic, stretch-relaxation stimuli on the expression of α
1
- and α
2
-subunits of Na
+
,K
+
-ATPase in vascular smooth muscle cells, we used the Flexercell strain unit to stretch rat aortic smooth muscle cells for several days on a collagen-coated silicone elastomer substratum. Six-second cycles of stretch-relaxation were applied to obtain 10% average surface elongation (22% maximum) for 4 days. Control cells were not stretched but were grown on a similar surface. The effect of Gd
3+
, a blocker of stretch-activated channels, was also investigated. At the end of 4 days, protein expression of α
1
- and α
2
-subunits was determined by Western blot analysis. Intensity of the bands for α
1
- and α
2
-subunits was quantified with the use of a computerized image analyzer. In the stretched cells, both the α
1
- and the α
2
-subunit protein-band intensities were significantly increased compared with those of the nonstretched cells. Treatment with 50 μmol/L Gd
3+
during the application of stretch prevented the upregulation of α
2
-expression but not that of α
1
-expression. Sodium pump activity, the functional counterpart of Na
+
,K
+
-ATPase, was inhibited as a result of stretch; Gd
3+
had no effect on this variable. Our results suggest that in vascular smooth muscle, stretch may be a signal for the upregulation of both the α
1
- and α
2
-isoforms. However, a differential response of the two isoforms to the blocker of stretch-activated channels implies involvement of different mechanisms. This alteration in protein expression is not reflected in the function of the enzyme.
Natriuretic Peptide Receptors in Human Artery and Vein and Rabbit Vein Graft
Authors: Ikeda Tadashi , Itoh Hiroshi , Komatsu Yasato , Hanyu Michiya , Yoshimasa Takaaki , Matsuda Katsuhiko , Nakao Kazuwa , Ban Toshihiko
Published: June 2012

Abstract
Natriuretic peptides elicit their biological effects by elevation of cGMP through activation of two biologically active receptors: natriuretic peptide A receptor, which shows high affinity to atrial and brain natriuretic peptides, and natriuretic peptide B receptor, which is specific to C-type natriuretic peptide. To elucidate the implications of the natriuretic peptide system in arteries and veins, we examined the cGMP production in response to atrial and C-type natriuretic peptides and gene expressions of biologically active natriuretic peptide receptors in human gastroepiploic artery, internal mammary artery, and saphenous vein. Atrial natriuretic peptide augmented cGMP production more potently by one order of magnitude in arteries than in veins. C-type natriuretic peptide stimulated cGMP production weakly and equally in these vessels. Analyzed by reverse transcription–polymerase chain reaction, gene expression of natriuretic peptide A receptor was four times more abundant in arteries than in veins. Gene expression of natriuretic peptide B receptor was approximately the same between these vessels. We also studied the responsiveness to atrial and C-type natriuretic peptide in rabbit jugular vein grafted into carotid artery. In arterialized vein grafts 4 weeks after operation, the effects of atrial and C-type natriuretic peptides on cGMP production did not change from those in jugular veins. In conclusion, atrial natriuretic peptide stimulates cGMP production more potently in arteries than in veins due to the preferential expression of natriuretic peptide A receptor in arteries. These observations support the distinct roles of natriuretic peptides in cardiovascular homeostasis.
Mechanisms of Transcriptional Synergism of Eukaryotic Genes
Authors: Thanos Dimitris
Published: June 2012

Abstract
The virus-inducible enhancer of the human interferon-β gene has served as an excellent example for the mechanisms controlling the activation and repression of transcription. This enhancer is activated by three different transcription factors that, with the help of the high mobility group protein HMG I(Y), assemble in a unique nucleoprotein complex that interacts as a unit with the basal transcriptional machinery. The assembly of unique enhancer complexes from similar sets of transcription factors may provide the specificity required for regulation of complex patterns of gene expression in higher eukaryotes.
Angiotensin II Is Mitogenic for Cultured Rat Glomerular Endothelial Cells
Authors: Wolf Gunter , Ziyadeh Fuad N. , Zahner Gunther , Stahl Rolf A.K.
Published: June 2012

Abstract
Angiotensin II (Ang II) has growth-stimulatory properties on different renal cell types. However, possible growth effects of this vasoactive peptide on endothelial cells isolated from the glomerular microvasculature have not formally been investigated. Therefore, we isolated and characterized primary cultures of rat glomerular endothelial cells. We used a simple technique in which collagenase-treated glomeruli were sparsely plated in several 96-well culture plates and microscopically screened for cobblestone-like outgrowth. After two limiting dilutions, homogeneous cultures were obtained. Cells were characterized by positive staining for the endothelial markers factor VIII, CD 31, endothelial leukocyte adhesion molecule-1, and the lectin
Bandeiraea simplificifolia
. Ang II stimulated the synthesis and release of endothelin-1 in culture supernatants. Moreover, in contrast to syngeneic mesangial cells, glomerular endothelial cells expressed angiotensin-converting enzyme. Ang II stimulated a mild but significant proliferation of quiescent cells, as measured by [
3
H]thymidine incorporation and direct cell counting. This mitogenesis was transduced by losartan-blockable angiotensin type 1 receptors. Moreover, Ang II mediated phosphorylation of mitogen-activated protein kinase 2 and induction of transcripts for the immediate early gene
Egr-1
. Our results indicate that Ang II is a moderate mitogen for primary cultures of rat glomerular endothelial cells and activation of these metabolically active cells may play a role in the pathophysiology of several types of glomerulonephritis. Moreover, remodeling of glomerular endothelial cells by Ang II may be important in the progression of structural renal damage during the course of hypertensive injury.
Hypertension Promotes Coronary Calcium Deposit in Asymptomatic Men
Authors: Megnien Jean Louis , Simon Alain , Lemariey Michel , Plainfossé Marie Christine , Levenson Jaime
Published: June 2012

Abstract
Despite its important role in coronary disease, coronary atherosclerosis has been poorly investigated in uncomplicated hypertension. Therefore, we evaluated the presence and amount (score) of coronary calcium with ultrafast computed tomography in 73 pairs of age-matched asymptomatic hypertensive or normotensive men. We also estimated the extent of peripheral atherosclerosis as the number of arterial sites (carotid, aortic, femoral) with echographic plaque. Compared with normotensive men, hypertensive men had more frequent coronary calcium (63% versus 47%), a higher calcium score (57±111 versus 18±38), and an odds ratio of calcium deposit of 1.95 (with confidence intervals [CI] 95%, 1.01 to 3.79) for any score and of 2.38 (95% CI, 1.02 to 5.52) or 4.84 (95% CI, 1.53 to 15.3) for scores above 50 or 100, respectively. Hypertensive men showed correlations of calcium score with age and hypertension duration but not with the height of blood pressure, and the odds ratio of calcium deposit between extensive and minor peripheral atherosclerosis was 4.67 (95% CI, 1.41 to 15.45) for any score and 8.63 (95% CI, 2.10 to 35.5) or 8.13 (95% CI, 1.64 to 40.3) for scores above 50 or 100. Thus, high blood pressure and in particular its duration rather than its value promotes the presence and overall extent of coronary calcium, a potential predictor of sudden coronary death, in parallel with the extent of peripheral atherosclerosis. The mechanisms of the interaction of hypertension and coronary calcification may be multifactorial and not specific to hypertension.
Menstrual Cycle Effects on Catecholamine and Cardiovascular Responses to Acute Stress in Black but Not White Normotensive Women
Authors: Mills Paul J. , Nelesen Richard A. , Ziegler Michael G. , Parry Barbara L. , Berry Charles C. , Dillon Elaine , Dimsdale Joel E.
Published: June 2012

Abstract
This study examined cardiovascular and catecholamine responses to two standardized laboratory stressors in 33 healthy age- and weight-matched black and white normotensive women (mean age, 32 years) during two phases of the menstrual cycle. Subjects were studied in a randomized order at the same time of day on two separate occasions approximately 6 weeks apart, once during the follicular phase (days 7 to 10 after menses) and once during the luteal phase (days 7 to 10 after the leutenizing hormone surge) of the menstrual cycle. Black women had higher systolic (
P
=.01) and diastolic (
P
=.01) pressures compared with white women. Black women showed greater diastolic pressure (
P
<.01) and plasma epinephrine (
P
<.05) responses to stress during the follicular compared with the luteal phase of the menstrual cycle; white women showed no significant changes in these variables. The findings extend the literature on race differences in responsivity to stress and indicate that in contrast to white women, reproductive hormones do influence cardiovascular and catecholamine responsivity to stress in black women.
Community-Based Education Classes for Hypertension Control
Authors: Iso Hiroyasu , Shimamoto Takashi , Yokota Kimiko , Sankai Tomoko , Jacobs David R. , Komachi Yoshio
Published: June 2012

Abstract
Community-based hypertension control is important for primary prevention of cardiovascular disease. In this study, untreated men and women aged 35 to 69 years were randomly assigned to an intervention (n=56) or control (n=55) group in a 1.5-year community-based education program. Subjects had no evidence of hypertensive end-organ defects and had screening blood pressures of 140 to 179 mm Hg systolic and/or 90 to 109 mm Hg diastolic, with no difference in mean blood pressure between groups (148 to 150 mm Hg for mean systolic and 83 to 84 mm Hg for mean diastolic pressures). The intervention group took four education classes in the first 6 months and four classes during the next year, and the control group took two classes. Health education focused on reduced dietary sodium and increased milk intake, brisk walking, and, if necessary, reduction of alcohol and sugar intakes. Antihypertensive medication was started less often in the intervention than in the control group at 1.5 years (9% versus 24%,
P
<.05). Mean systolic pressure was 5 to 6 mm Hg less in the intervention than in the control group at both 6 months and 1.5 years (
P
<.05), with or without inclusion of those subjects who began antihypertensive medication. Diastolic pressure and body mass index did not change significantly between groups. Urinary sodium excretion declined in the intervention but not in the control group (differences between groups:
P
=.04 at 6 months and
P
=.07 at 1.5 years). According to a behavioral questionnaire, sodium reduction and milk increase were greater in the intervention than the control group (sodium:
P
<.01 at 6 months and
P
=.08 at 1.5 years; milk:
P
<.001 at 6 months and
P
<.01 at 1.5 years). Mean ethanol intake was reduced in the intervention but not the control group (
P
=.04 at 1.5 years). This community-based hypertension control program was effective in reducing systolic pressure levels by nonpharmacological means during the first 6 months and maintaining the reduction for 1.5 years.
Wave Propagation in Coupled Left Ventricle–Arterial System
Authors: Berger David S. , Robinson Kimberly A. , Shroff Sanjeev G.
Published: June 2012

Abstract
The objective of this study was to examine the effects of wave propagation properties (global reflection coefficient, Γ

G

; pulse wave velocity,
c

ph

; and characteristic impedance,
Z

o

) on the mechanical performance of the coupled left ventricle–arterial system. Specifically, we sought to quantify effects on aortic pressure (
P

ao

) and flow (
Q

ao

) while keeping constant other determinants of
P

ao

and
Q

ao

(left ventricular end-diastolic volume,
V

ed

, and contractility, heart rate, and peripheral resistance,
R

s

). Isolated rabbit hearts were subjected to real-time, computer-controlled physiological loading. The arterial circulation was modeled with a lossless tube terminating in a complex load. The loading system allowed for precise and independent control of all arterial properties as evidenced by accurate reproduction of desired input impedances and computed left ventricular volume changes. While propagation phenomena affected
P

ao

and
Q

ao

morphologies as expected, their effects on absolute
P

ao

values were often contrary to the current understanding. Diastolic (
P

d

) and mean (
P

m

)
P

ao

and stroke volume decreased monotonically with increases in Γ

G

,
c

ph

, or
Z

o

over wide ranges. In contrast, these increases had variable effects on peak systolic
P

ao

(
P

s

): decreasing with Γ

G

, biphasic with
c

ph

, and increasing with
Z

o

. There was an interaction between Γ

G

and
c

ph

such that Γ

G

effects on
P

m

and
P

d

were augmented at higher
c

ph

and vice versa. Despite large changes in system parameters, effects on
P

m

and
P

s

were modest (<10% and <5%, respectively); effects on
P

d

were always two to four times greater. Similar results were obtained when the single-tube model of the arterial system was replaced by an asymmetrical T-tube configuration. Our data do not support the prevailing hypothesis that
P

s

(and therefore ventricular load) can be selectively and significantly altered by manipulating Γ

G

,
c

ph

, and/or
Z

o

.
Inhibition of 11β-Hydroxysteroid Dehydrogenase in Pregnant Rats and the Programming of Blood Pressure in the Offspring
Authors: Lindsay Robert S. , Lindsay R. Mark , Edwards Christopher R.W. , Seckl Jonathan R.
Published: June 2012

Abstract
Recent epidemiological studies have linked low birth weight with the later occurrence of cardiovascular and metabolic disorders, particularly hypertension. We have proposed that fetal exposure to excess maternal glucocorticoids may underpin this association. Normally, the fetus is protected from maternal glucocorticoids by placental 11β-hydroxysteroid dehydrogenase (11β-HSD). We have previously shown that treatment of pregnant rats with dexamethasone, a synthetic glucocorticoid that is poorly metabolized by the enzyme, reduces birth weight and produces elevated blood pressure in the adult offspring. Moreover, low activity of placental 11β-HSD correlates with low birth weight in rats. Here, we show that maternal administration of carbenoxolone, a potent inhibitor of 11β-HSD, throughout pregnancy leads to reduced birth weight (mean 20% decrease) and elevated blood pressures (increase in mean arterial pressure, 9 mm Hg in males, 7 mm Hg in females) in the adult offspring of carbenoxolone-treated rats. This effect requires the presence of maternal adrenal products, as carbenoxolone given to adrenalectomized pregnant rats had no effect on birth weight or blood pressure. These data support the hypothesis that excess exposure of the fetoplacental unit to maternal glucocorticoids reduces birth weight and programs subsequent hypertension and indicate a key role for placental 11β-HSD in controlling such exposure.
A Diuretic Is More Effective Than a β-Blocker in Hypertensive Patients Not Controlled on Amlodipine and Lisinopril
Authors: Antonios Tarek F. T. , Cappuccio Francesco P. , Markandu Nirmala D. , Sagnella Giuseppe A. , MacGregor Graham A.
Published: June 2012

Abstract
The combination of an angiotensin-converting enzyme inhibitor and a calcium antagonist has a synergistic effect in patients with more severe hypertension. However, when this combination fails to control blood pressure, it is not clear which drug is then additive. The aim of this work was to study in a double-blind, randomized, crossover design the effect on blood pressure of the addition of either a thiazide diuretic (bendrofluazide, 5 mg once daily) or a β-blocker (atenolol, 100 mg once daily) or placebo each for a month in hypertensive patients who are not adequately controlled on the combined treatment of amlodipine 5 mg once daily and lisinopril 5 mg twice daily. Eighteen patients with a supine diastolic pressure of more than 90 mm Hg after at least 1 month on the combined treatment of amlodipine and lisinopril were enrolled in the study. The results show that in patients whose blood pressures are not controlled by the combination of amlodipine and lisinopril, the addition of bendrofluazide 5 mg once daily causes a significant fall in blood pressure compared with placebo and a significantly greater fall than 100 mg atenolol once daily.
Renal Cytochrome P4504A Activity and Salt Sensitivity in Spontaneously Hypertensive Rats
Authors: Stec David E. , Trolliet Maria R. , Krieger Jose E. , Jacob Howard J. , Roman Richard J.
Published: June 2012

Abstract
Differences in the renal metabolism of arachidonic acid by cytochrome P450 have been reported in the spontaneously hypertensive rat (SHR) and Wistar-Koyto rats, but the contribution of this system to the development of hypertension is unclear. The present study compared renal P450 activity and blood pressure in SHR and Brown-Norway rats (BN) under control conditions and in response to an elevation in sodium intake; genetic linkage analysis was performed in an F
2
population (n=219) derived from these strains. Basal renal P4504A enzyme activity measured by conversion of [
14
C]arachidonic acid to 20-hydroxyeicosatetraenoic acid (20-HETE) was significantly greater in the kidneys of adult SHR (n=7) than of BN (n=8) (82±7 versus 60±5 pmol/min per milligram protein). Renal 20-HETE production fell 45% in SHR and 22% in BN in which salt intake was elevated by drinking of saline instead of water for 2 weeks. Mean arterial pressure averaged 157±3 mm Hg in SHR (n=9) and 100±2 mm Hg in BN fed a normal salt diet, and it rose to 170±7 mm Hg (
P
<.05) in SHR and fell to 90±3 mm Hg (
P
<.05) in BN (n=8) after sodium intake was elevated. A polymorphic marker, D5Rjr1, that spanned a repeated element in the P4504A1 gene on chromosome 5, where all three P4504A isoforms are located, was used for genotyping of the F
2
population. The P4504A genotype did not cosegregate with baseline mean arterial pressure in the F
2
population; however, significant linkage was observed with the change in mean arterial pressure after sodium intake of the rats was elevated. The degree of linkage differed in male and female rats, and the highest LOD score (3.6) was observed in male F
2
rats with a BN grandfather. These findings suggest that the difference in renal P450 activity in SHR and BN does not contribute to the development of hypertension in this F
2
population, but it may play some role in determining the blood pressure response to an elevation in salt intake.
Insulin-Resistant Lipolysis in Abdominally Obese Hypertensive Individuals
Authors: Hennes Magda M.I. , O'Shaughnessy Irene M. , Kelly Thomas M. , LaBelle Patrice , Egan Brent M. , Kissebah Ahmed H.
Published: June 2012

Resistance to the capacity of insulin to suppress lipolysis may be an important link in the association between abdominal obesity and hypertension. Furthermore, a more active renin-angiotensin system in adipose tissue may contribute to insulin-resistant lipolysis in abdominally obese hypertensive subjects. We determined nonesterified fatty acid concentrations and turnover as well as lipid oxidation under basal conditions and during steady-state euglycemia with two levels of insulinemia (72 and 287 pmol/L) in lean normotensive, abdominally obese normotensive, and abdominally obese hypertensive subjects. To assess the role of the renin-angiotensin system in determining nonesterified fatty acid turnover, we repeated studies in the abdominally obese hypertensive subjects after double-blind random assignment to placebo or enalapril for 1 month each. The main findings were the following: (1) Nonesterified fatty acid flux was significantly higher in abdominally obese hypertensive subjects at both levels of insulinemia than in either abdominally obese normotensive or lean normotensive subjects and correlated significantly with both mean blood pressure and total systemic resistance during the higher level of insulinemia. (2) Enalapril significantly improved insulin-resistant lipolysis in the abdominally obese hypertensive subjects. The improvement in insulin suppressibility of nonesterified fatty acid flux at the high hormonal concentrations correlated positively with the magnitude of reduction in blood pressure. (3) Basal lipid oxidation and suppression in response to insulin were similarly impaired in both obese groups. Resistance to the antilipolytic actions of insulin is thus a characteristic feature in abdominally obese hypertensive subjects and may be linked to the elevated blood pressure in these individuals. A more active renin-angiotensin system may partly explain the insulin-resistant lipolysis in this form of hypertension.
Altered Cerebrovascular Response to a Potassium Channel Opener in Hypertensive Rats
Authors: Takaba Hitonori , Nagao Tetsuhiko , Ibayashi Setsuro , Kitazono Takanari , Fujii Kenichiro , Fujishima Masatoshi
Published: June 2012

We examined whether the effect of Y-26763, an ATP-sensitive potassium channel opener, on cerebral blood flow is altered in stroke-prone spontaneously hypertensive rats (SHRSP) and, if altered, whether long-term antihypertensive treatment with cilazapril, an angiotensin-converting enzyme inhibitor, is capable of preventing the change. Cerebral blood flow during intracarotid infusion of Y-26763 was measured in anesthetized SHRSP and normotensive Wistar-Kyoto rats (WKY) as control. Y-26763 increased cerebral blood flow in a dose-dependent manner in WKY, and glibenclamide, a selective inhibitor of ATP-sensitive potassium channels, inhibited the Y-26763–induced increase in cerebral blood flow. In contrast, the response to Y-26763 in SHRSP was significantly impaired compared with that in WKY. Antihypertensive treatment with cilazapril lowered blood pressure toward normal and prevented the impaired response in cerebral blood flow to Y-26763 in SHRSP. These findings suggest that (1) ATP-sensitive potassium channels contribute to the regulation of cerebral blood flow in rats, (2) the response to an ATP-sensitive potassium channel opener is markedly diminished in hypertensive rats, and (3) the altered response to an ATP-sensitive potassium channel opener during chronic hypertension can be prevented by long-term antihypertensive treatment.
Relationship Between Left Ventricular Geometry and Natriuretic Peptide Levels in Essential Hypertension
Authors: Nishikimi Toshio , Yoshihara Fumiki , Morimoto Atsushi , Ishikawa Kazuhiko , Ishimitsu Toshihiko , Saito Yoshihiko , Kangawa Kenji , Matsuo Hisayuki , Omae Teruo , Matsuoka Hiroaki
Published: June 2012

Previous studies have shown that plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are increased in essential hypertension. However, whether left ventricular geometry affects plasma ANP and BNP levels remains unknown. To investigate the effect of left ventricular geometry on plasma ANP and BNP levels in essential hypertension, we measured plasma ANP and BNP levels in 90 patients with essential hypertension. All patients were hospitalized, and fasting blood samples were obtained in the early morning after 30 minutes of bed rest. Plasma ANP and BNP levels were measured by immunoradiometric assay. Hypertensive patients were classified into four groups according to echocardiographic findings that showed normal geometry, concentric remodeling, eccentric hypertrophy, or concentric hypertrophy. Mean plasma ANP and BNP levels in all essential hypertensive patients were higher than those in age-matched normotensive control subjects. Plasma ANP levels in hypertensive patients with concentric remodeling, eccentric hypertrophy, and concentric hypertrophy were higher than in normotensive control subjects, although there were no differences between normotensive subjects and hypertensive patients with normal geometry. Plasma BNP levels tended to be higher in hypertensive patients with normal geometry, concentric remodeling, and eccentric hypertrophy than in normotensive control subjects; however, the differences were not significant. Plasma BNP levels and BNP/ANP ratio were specifically higher in concentric hypertrophy. There were significant correlations between ANP and left ventricular mass index, relative wall thickness, interventricular septal thickness, posterior wall thickness, and mean arterial pressure. Plasma BNP levels significantly correlated with relative wall thickness, interventricular septal thickness, posterior wall thickness, and left ventricular mass index but not with mean arterial pressure. In addition, plasma BNP levels were well correlated with ANP levels, and the slope for the linear regression model was steeper in concentric hypertrophy than in the other four groups. These results show that plasma ANP and BNP levels are increased in essential hypertensive patients with left ventricular hypertrophy. Furthermore, BNP secretion is augmented to a greater extent in concentric hypertrophy. Thus, measurement of plasma ANP and BNP levels may be useful for the detection of concentric left ventricular hypertrophy in patients with essential hypertension.
Correlates of the Hemodynamic Determinants of Blood Pressure
Authors: Daniels Stephen R. , Kimball Thomas R. , Khoury Philip , Witt Sandra , Morrison John A.
Published: June 2012

The purpose of this study was to investigate the association of sex, race, lean body mass, and fat mass with the hemodynamic determinants of blood pressure, including stroke volume, heart rate, and total peripheral vascular resistance. The study included 201 subjects aged 6 to 17 years, 105 of whom were male and 98 of whom were black. Lean body mass and fat mass were both significant (
P
<.05) independent determinants of stroke volume, cardiac output, and total peripheral vascular resistance. However, the direction of the effect of lean body mass was opposite for stroke volume and cardiac output compared with that of total peripheral vascular resistance. The direct relationship of lean body mass with systolic blood pressure (SBP) and diastolic blood pressure (DBP) (regression coefficients, 0.55±0.05 for SBP and 0.47±0.05 for DBP) indicates that the effect of lean body mass on cardiac output may predominate. Lean body mass explained substantially more of the variance of the hemodynamic variables than did fat mass. After control for the effects of body size, male subjects had higher heart rate and cardiac output, and female subjects had higher vascular resistance. White subjects had higher stroke volume and cardiac output, and black subjects had higher peripheral vascular resistance. This study demonstrates that lean body mass is a more important correlate of the hemodynamic determinants of blood pressure than is fat mass and that sex and race have significant independent relationships with the hemodynamic determinants of blood pressure in children and adolescents.