bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Vascular Adaptation to Chronic Aortic Regurgitation on Left Ventricular Performance
Authors: Devlin William H. , Petrusha Janet , Briesmiester Kerri , Montgomery Daniel , Starling Mark R.
Published: June 2012

Background
—This investigation was designed to test the hypothesis that vascular adaptation occurs in patients with chronic aortic regurgitation to maintain left ventricular (LV) performance.

Methods and Results
—Forty-five patients with chronic aortic regurgitation (mean age 50±14 years) were studied using a micromanometer LV catheter to obtain LV pressures and radionuclide ventriculography to obtain LV volumes during multiple loading conditions and right atrial pacing. These 45 patients were subgrouped according to their LV contractility (E
es
) and ejection fraction values. Group I consisted of 24 patients with a normal E
es
. Group IIa consisted of 10 patients with impaired E
es
values (E
es
<1.00 mm Hg/mL) but normal LV ejection fractions; Group IIb consisted of 11 patients with impaired contractility and reduced LV ejection fractions. The left ventricular-arterial coupling ratio, E
es
/E
a,
where E
a
was calculated by dividing the LV end-systolic pressure by LV stroke volume, averaged 1.60±0.91 in Group I. It decreased to 0.91±0.27 in Group IIa (
P
<0.05 versus Group I), and it decreased further in Group IIb to 0.43±0.24 (
P
<0.001 versus Groups I and IIa). The LV ejection fractions were inversely related to the E
a
values in both the normal and impaired contractility groups (
r
=−0.48,
P
<0.05 and
r
=−0.56,
P
<0.01, respectively), although the slopes of these relationships differed (
P
<0.05). The average LV work was maximal in Group IIa when the left ventricular-arterial coupling ratio was near 1.0 because of a significant decrease in total arterial elastance (
P
<0.01 versus Group I). In contrast, the decrease in the left ventricular-arterial coupling ratio in Group IIb was caused by an increase in total arterial elastance, effectively double loading the LV, contributing to a decrease in LV pump efficiency (
P
<0.01 versus Group IIa and
P
<0.001 versus Group I).

Conclusions
—Vascular adaptation may be heterogeneous in patients with chronic aortic regurgitation. In some, total arterial elastance decreases to maximize LV work and maintain LV performance, whereas in others, it increases, thereby double loading the LV, contributing to afterload excess and a deterioration in LV performance that is most prominent in those with impaired contractility.
Addition of Angiotensin II Receptor Blockade to Maximal Angiotensin-Converting Enzyme Inhibition Improves Exercise Capacity in Patients With Severe Congestive Heart Failure
Authors: Hamroff Glenn , Katz Stuart D. , Mancini Donna , Blaufarb Ira , Bijou Rachel , Patel Rajoo , Jondeau Guillaume , Olivari Maria-Teresa , Thomas Sylvia , Le Jemtel Thierry H.
Published: June 2012

Background
—Incomplete suppression of the renin-angiotensin system during long-term ACE inhibition may contribute to symptomatic deterioration in patients with severe congestive heart failure (CHF). Combined angiotensin II type I (AT
1
) receptor blockade and ACE inhibition more completely suppresses the activated renin-angiotensin system than either intervention alone in sodium-depleted normal individuals. Whether AT
1
receptor blockade with losartan improves exercise capacity in patients with severe CHF already treated with ACE inhibitors is unknown.

Methods and Results
—Thirty-three patients with severe CHF despite treatment with maximally recommended or tolerated doses of ACE inhibitors were randomized 1:1 to receive 50 mg/d losartan or placebo for 6 months in addition to standard therapy in a multicenter, double-blind trial. Peak aerobic capacity (V̇
o
2
) during symptom-limited treadmill exercise and NYHA functional class were determined at baseline and after 3 and 6 months of double-blind therapy. Peak V̇
o
2
at baseline and after 3 and 6 months were 13.5±0.6, 15.1±1.0, and 15.7±1.1 mL · kg
−1
· min
−1
, respectively, in patients receiving losartan and 14.1±0.6, 14.3±0.9, and 13.6±1.1 mL · kg
−1
· min
−1
, respectively, in patients receiving placebo (
P
<0.02 for treatment group–by-time interaction). Functional class improved by at least one NYHA class in 9 of 16 patients receiving losartan and 1 of 17 patients receiving placebo.

Conclusions
—Losartan enhances peak exercise capacity and alleviates symptoms in patients with CHF who are severely symptomatic despite treatment with maximally recommended or tolerated doses of ACE inhibitors.
Demonstration of Rapid Onset Vascular Endothelial Dysfunction After Hyperhomocysteinemia
Authors: Chambers John C. , McGregor Andrew , Jean-Marie Jeff , Obeid Omar A. , Kooner Jaspal S.
Published: June 2012

Background
—Hyperhomocysteinemia is a major and independent risk factor for vascular disease. The mechanisms by which homocysteine promotes atherosclerosis are not well understood. We hypothesized that elevated homocysteine concentrations are associated with rapid onset endothelial dysfunction, which is mediated through oxidant stress mechanisms and can be inhibited by the antioxidant vitamin C.

Methods and Results
—We studied 17 healthy volunteers (10 male and 7 female) aged 33 (range 21 to 59) years. Brachial artery diameter responses to hyperemic flow (endothelium dependent), and glyceryltrinitrate (GTN, endothelium independent) were measured with high resolution ultrasound at 0 hours (fasting), 2 hours, and 4 hours after (1) oral methionine (L-methionine 100 mg/kg), (2) oral methionine preceded by vitamin C (1
g
/day, for 1 week), and (3) placebo, on separate days and in random order. Plasma homocysteine increased (0 hours, 12.8±1.4; 2 hours, 25.4±2.5; and 4 hours, 31.2±3.1 μmol/l,
P
<0.001), and flow-mediated dilatation fell (0 hours, 4.3±0.7; 2 hours, 1.1±0.9; and 4 hours, −0.7±0.8%) after oral L-methionine. There was an inverse linear relationship between homocysteine concentration and flow-mediated dilatation (
P
<0.001). Pretreatment with vitamin C did not affect the rise in homocysteine concentrations after methionine (0 hours, 13.6±1.6; 2 hours, 28.3±2.9; and 4 hours, 33.8±3.7 μmol/l,
P
=0.27), but did ameliorate the reduction in flow-mediated dilatation (0 hours, 4.0±1.0; 2 hours, 3.5±1.2 and 4 hours, 2.8±0.7%,
P
=0.02). GTN-induced endothelium independent brachial artery dilatation was not affected after methionine or methionine preceded by vitamin C.

Conclusions
—We conclude that an elevation in homocysteine concentration is associated with an acute impairment of vascular endothelial function that can be prevented by pretreatment with vitamin C in healthy subjects. Our results support the hypothesis that the adverse effects of homocysteine on vascular endothelial cells are mediated through oxidative stress mechanisms.
Effects of Hypertension, Diabetes Mellitus, and Hypercholesterolemia on Endothelin Type B Receptor–Mediated Nitric Oxide Release From Rat Kidney
Authors: Kakoki Masao , Hirata Yasunobu , Hayakawa Hiroshi , Tojo Akihiro , Nagata Daisuke , Suzuki Etsu , Kimura Kenjiro , Goto Atsuo , Kikuchi Kazuya , Nagano Tetsuo , Omata Masao
Published: June 2012

Background
—Although endothelin-1 is a potent vasoconstrictor peptide, stimulation of endothelin type B receptor (ETBR) causes bidirectional changes in vascular tone, ie, vasodilation and vasoconstriction. Roles of ETBR in pathological conditions are largely unknown.

Methods and Results
—We studied the effect of BQ-3020, a highly selective ETBR agonist, on renal vascular resistance and nitric oxide (NO) release in the isolated, perfused kidney of rats with hypertension, diabetes mellitus, and hypercholesterolemia. Immunohistochemistry of endothelial NO synthase and ETBR was also examined. Infusion of BQ-3020 at concentrations of ≤10
−10
mol/L reduced renal perfusion pressure in Dahl salt-resistant (R) rats but increased renal perfusion pressure in Dahl salt-sensitive (S) rats (10
−10
mol/L: −10.3±0.6% versus 11.2±1.5%, R versus S;
P
<0.01). BQ-3020 caused a dose-dependent release of NO in both R and S rats, although the level of NO release in S rats was lower, as detected by chemiluminescence (10
−10
mol/L: 10.7±0.7 versus 3.1±0.4 fmol/min per gram of kidney, R versus S;
P
<0.01). Similar effects of BQ-3020 were observed in streptozotocin-induced diabetic rats and diet-induced hypercholesterolemic rats. Expression of endothelial NO synthase decreased in S rats but not in diabetic or hypercholesterolemic rats. In contrast, expression of ETBR in the endothelium was decreased in all 3 disease models compared with that in the vascular smooth muscle cell.

Conclusions
—These results suggest that impaired NO release in response to stimulation of ETBR is due, at least in part, to a decrease in endothelial ETBR and may play a role in vascular dysfunction usually associated with arteriosclerosis-related diseases.
Regional Differences in the Recovery Course of Tachycardia-Induced Changes of Atrial Electrophysiological Properties
Authors: Lee Shih-Huang , Lin Fang-Yue , Yu Wen-Chung , Cheng Jun-Jack , Kuan Peiliang , Hung Chi-Ren , Chang Mau-Song , Chen Shih-Ann
Published: June 2012

Background
—Regional differences in recovery of tachycardia-induced changes of atrial electrophysiological properties have not been well studied.

Methods and Results
—In the control group (5 dogs), atrial effective refractory period (AERP) and inducibility of atrial fibrillation (AF) were assessed before and every 4 hours for 48 hours after complete atrioventricular junction (AVJ) ablation with 8-week VVI pacing. In experimental group 1 (15 dogs), AERP and inducibility of AF were assessed before and after complete AVJ ablation with 8-week rapid right atrial (RA) pacing (780 bpm) and VVI pacing. In experimental group 2 (7 dogs), AERP and inducibility of AF were assessed before and after 8-week rapid left atrial (LA) pacing and VVI pacing. AERP and inducibility and duration of AF were obtained from 7 epicardial sites. In the control group, atrial electrophysiological properties obtained immediately and during 48-hour measurements after pacing did not show any change. In the 2 experimental groups, recovery of atrial electrophysiological properties included a progressive recovery of AERP shortening, recovery of AERP maladaptation, and decrease of duration and episodes of reinduced AF. However, recovery of shortening and maladaptation of AERP and inducibility of AF was slower at the LA than at the RA and Bachmann’s bundle.

Conclusions
—The LA had a slower recovery of tachycardia-induced changes of atrial electrophysiological properties, and this might play a critical role in initiation of AF.
Angiopathic serum factor in perinephritic hypertensive dogs.
Authors: Simon G
Published: June 2012

To investigate the role of circulating humoral substances in the pathogenesis of increased vascular wall water and sodium concentration in experimental hypertension, rabbit aortic media explants were cultured in tissue culture medium supplemented (10-20%) with serum obtained from the same dogs (n = 7): 1) before the induction of hypertension; 2) after wrapping one kidney in silk (two-kidney perinephritic hypertension, 2-KPHT); and 3) after contralateral nephrectomy (1-KPHT). Cultures also were run with serum of sham-wrapped and then unilaterally nephrectomized normotensive dogs (n = 4). After 3 weeks of culture, the explants were harvested, and their water, sodium and potassium concentration was measured. Compared to the composition of explants cultured in prehypertensive serum, the water concentration of explants cultured in 1-KPHT and the sodium concentration of explants cultured in 2-KPHT and 1-KPHT serum were increased (p < 0.05). The water and electrolyte content of explants cultured in sera of sham-operated normotensive control dogs was the same regardless of the type of serum used, pre- or post-sham surgery or post-nephrectomy. The effects of serum from hypertensive dogs were not explained by variations in serum creatinine, sodium and potassium levels or in plasma renin activities. The experiments provide evidence for the role of serum factor(s) in the pathogenesis of abnormal vascular wall water and sodium concentration in experimental hypertension.
Raised cerebrospinal fluid norepinephrine in some patients with primary hypertension.
Authors: Eide I , Kolloch R , De Quattro V , Miano L , Dugger R , Van der Meulen J
Published: June 2012

To test whether central neurogenic factors participate in blood pressure elevation in primary hypertension, we studied the concentrations of: norepinephrine, epinephrine and dopamine-beta-hydroxylase (DBH) in cerebrospinal fluid (CSF); and norepinephrine, epinephrine, DBH and plasma renin activity (PRA) in plasma of 22 subjects (seven with primary hypertension, 11 normotensive patients with non-systemic neurological disorders, and four with secondary hypertension). Plasma and CSF norepinephrine (NE) were increased in primary hypertensives compared to normotensives. Cerebrospinal fluid norepinephrine was related to diastolic blood pressure, and systolic blood pressure when normotensive and primary hypertensives were taken together. The CSF norepinephrine of primary hypertensive patients was correlated with natural log PRA. The CSF norepinephrine was correlated inversely with age in primary hypertensive patients but not in the normotensive subjects. The low CSF norepinephrine and epinephrine, despite markedly increased plasma NE and epinephrine, in two patients with pheochromocytoma, indicate a blood-brain barrier for these neurohormones. The observations support the view that the central sympathetic nervous system is involved in the pathogenesis of primary hypertension, particularly in younger patients.
Regional myocyte size in normotensive and spontaneously hypertensive rats.
Authors: Bishop S P , Oparil S , Reynolds R H , Drummond J L
Published: June 2012

Regional differences in cell size in the hearts of rats with and without cardiac hypertrophy were studied using isolated muscle cells. Isolated cardiac myocytes were prepared from left ventricular free wall inner and outer halves and the right ventricle of six male 12-week-old spontaneously hypertensive (SHR), Wistar-Kyoto (WKY) and Fischer-344 rats. In SHR, blood pressure was increased to 188 +/- 4 (SEM) mm Hg versus 143 +/- 2 and 133 +/- 10 for WKY and Fischer rats, respectively (p less than 0.001). Total heart weight was increased to 1103 +/- 29 mg in SHR compared to 824 +/- 21 in WKY and 951 +/- 23 in Fischer rats (p less than 0.001. Isolated cardiac myocytes were prepared by perfusion of isolated hearts with Ca++ free Hanks' solution containing EGTA followed by collagenase-containing media. Mean length, width and volume of 150 cells stained with hematoxylin and eosin from each site were measured with a sonic digitizer. Two nuclei were present in 85 to 87% of isolated cells from all strains and regions. There was no difference among strains in right ventricular cell length, width, or volume, nor between left ventricular inner and outer halves within each strain. Left ventricular cells were larger than right ventricular cells (p less than 0.05) in all strains. Left ventricular cells of SHR were larger than left ventricular cells of WKY of Fischer rats in proportion to the increase in total heart weight, indicating that cardiac enlargement in SHR is due to increased cell size rather than increased cell number.
Estimating compliance with diuretic therapy: urinary hydrochlorothiazide-creatinine ratios in normal subjects.
Authors: Hodge R H , Lynch S S , Davison J P , Knight J G , Sinn J A , Carey R M
Published: June 2012

We gave 21 healthy young men 100 mg of hydrochlorothiazide daily to determine whether or not urinary detection of the drug was feasible as a measure of compliance on a standard antihypertensive regimen. All subjects took the drug daily for 6 days, after which they were divided into four groups with differing patterns of medication administration. Urine hydrochlorothiazide and creatinine measurements were obtained to validate the urinary hydrochlorothiazide-creatinine ratio (UHCR) as an accurate quantitative index of compliance. The subjects achieved a constant level of UHCR of 13 +/- 3.0 within 48 hours of hydrochlorothiazide administration. The UHCR levels decreased to 5.0 +/- 0.8 48 hours after discontinuation of the drug (p less than 0.001). UHCR values in the range of 13 +/- 6 indicate that the subject has ingested hydrochlorothiazide 24 hours previously. The UHCR is a potentially useful means of assessing compliance in hypertensive patients taking hydrochlorothiazide.
Symptomatic sick sinus syndrome due to guanethidine. Case report.
Authors: Rowe J , Bassan M M
Published: June 2012

A patient is described who developed symptomatic sinus bradycardia as low as 20 beats per minute and sinus arrest of up to 4.4 seconds while receiving guanethidine, 75 mg daily. The bradycardia resolved following discontinuation of the drug and reappeared upon challenge with it. Intrinsic disease of the sinoatrial and atrioventricular nodes was evidenced 3 weeks following discontinuation of the guanethidine by a borderline abnormally prolonged sinus node recovery time of 1500 msec and a PR interval of 0.28 seconds. Although sinus bradycardia is a known and not infrequent side effect of guanethidine, such an extreme form as seen in our patient appears to be quite rare, and may be related to the pre-existing disease of the conduction system.
Genetic influences on renin, aldosterone, and the renal excretion of sodium and potassium following volume expansion and contraction in normal man.
Authors: Grim C E , Miller J Z , Luft F C , Christian J C , Weinberger M H
Published: June 2012

To investigate the influence of hereditary on plasma renin activity (PRA), plasma aldosterone concentrations (PAC), blood pressure, and the renal excretion of sodium and potassium following volume expansion and contraction in normal man, we studied 37 pairs of monozygotic (MZ) and 18 pairs of dizygotic (DZ) twins. Volume expansion was achieved by the intravenous infusion of 2L normal saline; volume contraction was accomplished by a low-sodium diet and 120 mg oral furosemide. The presence of genetic variance was tested by calculating the within pair and among component estimates of genetic variance. Outpatient 24-hour-urine collections suggested that MZ and DZ twins ingested diets similar in sodium and potassium content, and failed to reveal genetic influences on the dietary preferences for these electrolytes. The PRA values suggested heritable influences during both the volume expanded and contracted state with the added stimulus of upright posture. Heritable influences were observed on PAC and were most apparent in the basal state on the day of volume expansion. An influence of heredity on blood pressure was most apparent during volume contraction. Urinary sodium excretion (UNaV), urinary potassium excretion (UKV), fractional excretion of sodium (FENa), and fractional excretion of potassium (FEK) revealed evidence of significant genetic variance under the condition of volume expansion. in that state, systolic blood pressure was directly correlated with PRA, PAC, and inversely with FENa. The data suggest that the renal regulation of sodium and potassium excretion is in part influenced by heritable factors that may in turn contribute to the development of hypertension in some individuals.
Rapid dextran infusion in essential hypertension.
Authors: Safar M E , London G M , Levenson J A , Simon A C , Chau N P
Published: June 2012

Hemodynamic parameters were studied before and after rapid dextran infusion in 34 men including 17 patients with sustained essential hypertension and 17 normotensive controls. In both groups of patients, dextran infusion induced a significant increase (p less than 0.001) in central venous pressure (CVP), cardiac output (CO), and stroke volume. The percent change in stroke volume was significantly higher in hypertensives (p less than 0.001) than in controls. Three indices of volume expansion were calculated: 1) the ratio between the change in CO and the change in volume, which was significantly higher in hypertensives (p less than 0.025), 2) the ratio between the change in CO and the change in CVP, which was similar in both groups, and 3) the ratio between the change in volume and the change in CVP, which was significantly reduced in hypertensives (p less than 0.001). In the overall population, the latter ratio was negatively correlated with the change in CO (or in stroke volume) induced by expansion ( r = -0.75). The results provided evidence that: 1) the slope of the relationship between CO and blood volume was steeper in hypertensives than in normotensives, and 2) the steeper slope was due to a reduction in the effective compliance of the vascular bed, causing a greater elevation in CO per unit rise in volume.
Tilt test in essential hypertension. Differential responses in heart rate and vascular resistance.
Authors: London G M , Weiss Y A , Pannier B P , Laurent S L , Safar M E
Published: June 2012

Changes in hemodynamic parameters following 50-degree head-up tilt were studied in a population of 56 men, including 35 subjects with sustained essential hypertension and 21 age-matched normotensive controls. The increase in heart rate following tilt was similar in groups and exhibited the same reduction in response with age. The increase in vascular resistance following tilt was strongly and positively correlated with both age and baseline vascular resistance. The latter finding was observed mainly in hypertensive subjects. The study provided evidence that differentiated responses of heart rate and vascular resistance may be observed following orthostasis. In both normal and hypertensive subjects, the age dependence of heart rate response possibly reflected differences in baroreceptor reflex control of parasympathetic and sympathetic activity. In hypertensive subjects, the vascular response was amplified with age and baseline vascular resistance, suggesting a role for structural changes of the vessels in the increased vascular response.
Decreased intraocular pressure in dogs with one-kidney, one wrapped hypertension.
Authors: Bell D R , Hollingsworth S F , Overbeck H W
Published: June 2012

We examined the relationship of intraocular pressure and the development of one-kidney, one wrapped (perinephritic) hypertension in the dog. Conscious femoral arterial pressure (direct arterial puncture) and intraocular pressure (Schiotz tonometer) were measured weekly before and after the surgical induction of hypertension in 11 healthy male mongrel dogs and before and after unilateral nephrectomy in 15 normotensive control dogs. Preoperative mean arterial pressure (102 +/- 5 vs 99 +/- 8 [SD] mm Hg, hypertensive vs control dogs) and intraocular pressure (18.1 +/- 2.5 vs 17.7 +/- 2.1 mm Hg, hypertensive vs control dogs) were similar in both groups. In normotensive control dogs, mean arterial pressure and intraocular pressure averaged over the postoperative period (4-8 weeks) did not differ significantly from preoperative values. In contrast, during the same period arterial pressure significantly increased and intraocular pressure significantly decreased in hypertensive dogs (arterial pressure, 163 +/- 8 mm Hg; intraocular pressure, 11.9 +/- 4.0 mm Hg; p less than 0.001 for both values compared with corresponding values in control dogs). Intraocular pressure was inversely related to arterial pressure in hypertensive dogs (r = 0.56, p less than 0.01). These observations indicate that intraocular pressure decreases with the development of canine one-kidney, one wrapped hypertension. The mechanism of this decrease may be related to abnormalities in Na+,K+-adenosine triphosphatase activity found in this form of hypertension.
Kinetic analysis of erythrocyte Na+-K+ pump and cotransport in essential hypertension.
Authors: Tuck M L , Corry D B , Maxwell M , Stern N
Published: June 2012

Alterations in red blood cell (RBC) Na+-K+ pump and Na+-K+ cotransport have been described in essential hypertension. We evaluated Na+-K+ pump and cotransport in 30 hypertensive and 26 normotensive subjects subdivided by race and family history of hypertension using an improved method to examine the kinetics of Na and K effluxes. RBCs were Na-loaded by the nystatin method to five different levels of internal Na with pump determined as ouabain-sensitive Na efflux and cotransport as furosemide-sensitive Na and K efflux. Two kinetic parameters were determined for both transport systems: the apparent affinity for Na (K0.5) and the velocity of efflux at saturating internal Na concentration (Vmax). Mean intracellular Na content in fresh RBCs (mmol/L cells) was higher in black hypertensive (12.6 +/- 1.8 mmol/L cells) and normotensive subjects (10.9 +/- 1.2 mmol/L cells) than in white hypertensive (8.7 +/- 1.0 mmol/L cells) or normotensive subjects (8.5 +/- 0.8 mmol/L cells). The Vmax and K0.5 for pump were not significantly different between study groups. The Vmax for cotransport was elevated in white hypertensive compared with normotensive subjects, but the K0.5 values were similar. Black normotensive and hypertensive subjects displayed a lower Vmax and increased K0.5 for cotransport compared with the white groups. A family history of hypertension had no influence on cotransport kinetics in blacks but did predict white normotensive and hypertensive subjects with low cotransport. The reduction in intracellular Na affinity for cotransport in black subjects may explain their higher intracellular Na in fresh RBCs.(ABSTRACT TRUNCATED AT 250 WORDS)
Clinical evaluation of patients with hypertension and exercise-induced renal dysfunction.
Authors: Clorius J H , Mann J , Schmidlin P , Strauss L G , Saur T , Irngartinger G
Published: June 2012

An exercise-mediated renal omicron-iodohippurate transport abnormality was recently identified in patients with hypertension. The disturbance was not observed in normotensive controls. To learn more about this transient functional disturbance of the kidney, we obtained gamma camera hippurate renograms in 45 patients with hypertension. The final diagnoses indicated that 27 patients had essential hypertension, 15 had renal parenchymal or renovascular hypertension, 2 had malignant hypertension, and 1 had hypertension of pregnancy. We documented age, height, weight, global and unilateral renal function, blood pressure status, and antihypertensive medication used at time of scintigraphy. We also noted the serum catecholamine, sodium, and potassium levels. All patients were scintigraphed at rest and during exercise. The scintigraphic examination documented exercise-induced renal dysfunction in 28 (62%) patients (abnormal exercise renogram), while 17 (38%) had renograms not noticeably influenced by the exercise protocol (normal exercise renogram). When the results of scintigraphy were compared with the clinical data, a weak correlation was found between patient overweight and an abnormal response to exercise. There was no significant difference between groups with normal and abnormal exercise renograms with respect to the other parameters assessed. Exercise renography was not useful for differentiating renal and essential hypertension. Renography appears to demonstrate an exercise-mediated, transient, renal perfusion disturbance in certain patients with hypertension. The examination appears to assess a new parameter in hypertensive disease. Thus, the gamma camera renogram should be reevaluated in the patient with hypertension.
Effect of dietary fats and carbohydrate on blood pressure of mildly hypertensive patients.
Authors: Sacks F M , Rouse I L , Stampfer M J , Bishop L M , Lenherr C F , Walther R J
Published: June 2012

The effect on blood pressure (BP) of replacing dietary saturated fat with either polyunsaturated fat (linoleic acid) or carbohydrate was studied in 21 untreated mildly hypertensive patients. In a randomized, double-blind, crossover protocol, all subjects received dietary supplements of cream, safflower oil, and carbohydrate in random sequence, each prepared in flavored yogurt or milk. Each supplement was administered for 6 weeks and followed by a 4-week washout period of no supplementation. Dietary linoleic acid increased from 4.6 to 13% of energy intake when the safflower oil replaced cream, while saturated fat decreased from 16 to 10%. Total fat intake was 37 to 38% during the cream and safflower oil periods but was 28% during the carbohydrate period. Compliance with the diets was demonstrated by significant changes in fasting plasma fatty acid measurements. Mean clinic BP was 135 +/- 9/93 +/- 6 mm Hg at baseline. There were no significant differences in BP measured in the clinic or at home among the three dietary periods. The protocol had more than 80% power to detect a mean effect of diet of 3 mm Hg systolic or 2 mm Hg diastolic BP. Therefore, replacing dietary saturated fat with carbohydrate or with linoleic acid does not affect BP in subjects with mild hypertension.
Hypersensitivity of phospholipase C in platelets of spontaneously hypertensive rats.
Authors: Koutouzov S , Remmal A , Marche P , Meyer P
Published: June 2012

Thrombin-induced aggregation and serotonin release were markedly enhanced in platelets from spontaneously hypertensive rats (SHR) when compared with those from normotensive Wistar-Kyoto rats (WKY). Since phosphoinositides are involved in calcium-mediated platelet responses, the metabolism of these lipids was investigated in SHR and WKY by using 32P-labeled quiescent platelets. In unstimulated cells, both the rate and extent of 32P incorporation into individual inositol-containing phospholipids and phosphatidic acid were identical in SHR and WKY. This finding suggests that the pool size and basal turnover of phosphoinositides did not differ between the two strains. In contrast, early thrombin-induced phosphoinositide metabolism, when monitored as changes in [32P]phosphatidic acid, was significantly higher in SHR than in WKY. For example, a 20-second exposure to thrombin, 0.3 U/ml, induced the formation of 1.6 times more [32P]phosphatidic acid in SHR than in WKY. These results provide evidence for a leftward shift of the dose-response and time-course curves of thrombin-induced [32P]phosphatidic acid formation in SHR. Moreover, the extent of the difference between SHR and WKY was independent of the extracellular calcium concentration. Following thrombin stimulation, [32P]phosphatidic acid formation likely reflects the initial agonist-receptor interaction; therefore, these results suggest that phospholipase C activity is enhanced in platelets of SHR and that the hypersensitivity of phospholipase C in SHR may play a role in the overall alteration of cell calcium handling and, hence, in the platelet responses of SHR.
Effects of race and marginally elevated blood pressure on responses to stress.
Authors: Light K C , Obrist P A , Sherwood A , James S A , Strogatz D S
Published: June 2012

A total of 228 men, aged 18 to 22 years (109 black and 119 white), underwent monitoring of heart rate (HR) and systolic (SBP) and diastolic blood pressure (DBP) responses during several stressor conditions and a 30-minute posttask rest period. Stressors included the cold pressor test and three reaction-time tasks: noncompetitive, competitive, and competitive plus money incentive. Substantial within-subject variations in blood pressure and heart rate were induced, varying from 119/70 to 148/94 mm Hg and from 63 to 91 beats/min on the average. Men (25 black and 39 white) with marginal SBP elevations during initial casual determinations had higher SBP under all conditions compared with men whose casual SBP levels were normal, and they also showed greater elevations over baseline levels in heart rate, SBP, and DBP during the stressors and the initial casual determination. Black and white subjects did not differ in their blood pressures at baseline or during the initial casual determinations, although blacks had slightly lower heart rates. Blacks did show greater SBP elevations over baseline levels than whites during the stressors, primarily because the blacks with marginally elevated SBP showed substantially greater stress-induced increases than whites with marginally elevated SBP. This enhanced pressor response to stress in blacks with marginal blood pressure elevations may be due to higher vascular resistance during enhanced sympathetic activity and could contribute to the higher incidence of hypertension among blacks.
Age, race, diagnosis, and sodium effects on the pressor response to infused norepinephrine.
Authors: Dimsdale J E , Graham R M , Ziegler M G , Zusman R M , Berry C C
Published: June 2012

We studied the blood pressure responses to infused norepinephrine in 34 normotensive and 21 unmedicated subjects with essential hypertension. The two groups were similar in age, relative body weight, and urinary electrolyte excretion. Patients were studied on two extremes of dietary salt (200 mEq Na and 10 mEq Na per day). The dose-response curves were highly linear (p less than 0.00001) for both systolic and diastolic blood pressures. There was no evidence for an increased sensitivity to infused norepinephrine among the hypertensive subjects. On the other hand, older subjects had steeper slopes (p less than 0.005). Subjects on a high salt diet had steeper slopes than those on low salt diets (p less than 0.0025); this trend was especially apparent among blacks (p less than 0.005). Black and white hypertensive subjects responded to the high salt diet in opposite fashion: The blacks showed an increased pressor sensitivity (p less than 0.05), whereas the whites demonstrated a nonsignificant decreased pressor sensitivity. These results indicate that age, race, and salt effects must be meticulously controlled in studies of sympathetic nervous system physiology.
Antihypertensive and hypotensive effects of atrial natriuretic factor in men.
Authors: Weder A B , Sekkarie M A , Takiyyuddin M , Schork N J , Julius S
Published: June 2012

Synthetic atrial natriuretic factor (ANF) was administered in ascending doses (0.03, 0.20, 0.45 microgram/kg/min) to eight mildly essential hypertensive men on high (200 mEq/day) or low (10 mEq/day) sodium diets. Responses of blood pressure, heart rate, urinary volume and electrolyte excretion, renin, and aldosterone were measured. For the entire group, ANF lowered blood pressure and increased heart rate during the 0.20 and 0.45 microgram/kg/min infusions, and the antihypertensive effect of the peptide persisted for at least 2 hours after the infusions ended. Four patients (2 at 0.20 microgram/kg/min and 2 at 0.45 microgram/kg/min) experienced sudden bradycardia and hypotension at the end of or shortly after completion of ANF infusion. Renal excretion of water, sodium, chloride, calcium, and phosphorus increased in a dose-dependent fashion in response to infused ANF. Patients on the 200 mEq/day sodium diet had greater increases in urinary volume (11.1 +/- 2.8 vs 3.0 +/- 2.0 ml/min; p less than 0.05), sodium (870 +/- 134 vs 303 +/- 27 microEq/min; p less than 0.05), and chloride (801 +/- 135 vs 176 +/- 75 microEq/min; p less than 0.02) compared with patients on the low sodium diet. The apparent direct suppressive effect of a 0.03 microgram/kg/min infusion of ANF on renin and aldosterone levels was overcome at higher doses by counterregulation provoked by the depressor action. Renin was slightly (-12%) suppressed during the 0.03 microgram/kg/min infusion of ANF but increased at the 0.20 (+50%) and 0.45 microgram/kg/min (+90%; p less than 0.03) rates. Aldosterone declined significantly during the 0.03 microgram/kg/min infusion (-45%; p less than 0.01) of ANF but not during the two higher dose infusions.(ABSTRACT TRUNCATED AT 250 WORDS)
Increased rigidity of red blood cell membrane in young spontaneously hypertensive rats.
Authors: Chabanel A , Schachter D , Chien S
Published: June 2012

The micropipette test was used to study the effects of age on the elasticity of red blood cell (RBC) membrane in spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar-Kyoto rats (WKY), ranging from 3 to 23 weeks of age. The development of hypertension in the SHR started at 3 weeks and was fully established at 7 to 8 weeks. In the developmental phase of hypertension (3-5 weeks), the SHR showed a significant increase in RBC membrane elastic modulus (i.e., a decrease in RBC membrane deformability) when compared with the age-matched normotensive control rats (WKY). After the establishment of hypertension (7-8 weeks), however, the deformability of the RBC membrane of SHR improved and became comparable to that of the WKY. These results indicate that abnormal erythrocyte membrane elasticity is an early event in SHR and that adaptive recovery occurs when hypertension is fully developed.
Purification and partial characterization of canine angiotensinogen.
Authors: Oliver J A
Published: June 2012

A procedure is described to isolate angiotensinogen (renin substrate) from canine plasma. The isolation procedure resulted in an 800-fold purification with a rate of recovery of approximately 12%. The purified protein has a specific activity of 24 micrograms of angiotensin I/mg protein. The amino terminal amino acid sequence of canine angiotensinogen was found to be identical to that of the horse but to differ from that of human and rat angiotensinogens. Canine angiotensinogen was heterogeneous with respect to molecular weight and isoelectric point. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of pure angiotensinogen revealed two closely spaced bands with apparent molecular weights of 58,000 and 56,000. Chromatofocusing showed four isoforms: Peaks of pure angiotensinogen eluted at pH levels of 4.32, 4.23, 4.15, and 4.04. Isoelectric focusing confirmed the presence of four isoforms. Thus, the purification procedure identified two molecular weight forms and four isoforms of canine angiotensinogen. Isolation of the four isoforms will allow their characterization and the study of their physiological significance.
Sodium transport parameters in erythrocytes of patients with primary aldosteronism.
Authors: Smith J B , Wade M B , Fineberg N S , Weinberger M H
Published: June 2012

Primary aldosteronism is an uncommon cause of hypertension but one of particular interest because of its distinctive pathophysiological mechanism of blood pressure elevation. Aldosterone has been associated with increased Na+,K+-adenosine triphosphatase (ATPase) activity, but there is controversy over which sodium transport parameters are responsible for this increase. We measured intracellular sodium, ouabain-sensitive and ouabain-insensitive sodium efflux, and the number of Na+,K+-ATPase sites of washed erythrocytes, as well as Na+-Li+ countertransport and the Li+-K+ cotransport rate constant of lithium-loaded red blood cells (RBCs) in six patients with primary aldosteronism and in 50 normal subjects. Ouabain-sensitive sodium efflux was significantly (p less than 0.001) higher for the primary aldosteronism patients than for normal subjects (1.85 +/- 0.29 vs 1.51 +/- 0.21 mmol/L RBC/hr) even though the intracellular sodium concentration (7.2 +/- 1.5 vs 6.7 +/- 1.9 mM) and the number of the Na+,K+-ATPase sites per RBC (331 +/- 52 vs 385 +/- 97) were not increased. The elevated sodium efflux appeared to be due to a significant (p less than 0.001) increase in the rate constant (1.60 +/- 0.12 x 10(-15) vs 1.28 +/- 0.15 x 10(-15) mmol/site/hr) of the ouabain-sensitive sodium efflux. The rate constant decreased significantly (p less than 0.01) after treatment.
Mechanism of inhibition of human renin by monoclonal antibodies.
Authors: de Gasparo M M , Wood J M , Heusser C H
Published: June 2012

The mechanism by which monoclonal antibodies directed against human renin (R3-36-16 and R3-47-10) inhibit renin activity was investigated using various substrates. Both antibodies acted as potent inhibitors of human renin activity when human angiotensinogen was used as a substrate. However, their effects differed clearly in the presence of synthetic tetradecapeptide. When low concentrations of tetradecapeptide were used as substrate, renin activity was only partially inhibited by R3-47-10, whereas it was stimulated by R3-36-16. At higher synthetic substrate concentrations, both antibodies stimulated angiotensin I production. This effect was independent of the pH. Both antibodies exerted their effects in the presence of CGP 29287, a peptidic transition-state competitive renin inhibitor, indicating that their binding sites differed from that of CGP 29287. In combination, the stimulatory effect of R3-36-16 was not blocked by R3-47-10, but the inhibition produced by R3-47-10 was reversed by R3-36-16. Both antibodies may prevent the large natural substrate angiotensinogen from entering the enzymatic cleft by steric hindrance. At a low substrate concentration, R3-47-10 may also partially hinder the access of synthetic tetradecapeptide into the active cleft by steric hindrance. In contrast, the stimulating effect of both antibodies may be due to a conformational change in the renin molecule, allowing an increased access of tetradecapeptide or a more rapid release of the product from the enzymatic cleft.
Hypertension, non-insulin-dependent diabetes, and intracellular sodium metabolism.
Authors: Trevisan M , Vaccaro O , Laurenzi M , De Chiara F , Di Muro M , Iacone R , Franzese A
Published: June 2012

The present study was designed to investigate whether non-insulin-dependent diabetic hypertensive patients exhibit abnormalities in intracellular sodium metabolism similar to those described for essential hypertensive patients. Both normotensive and hypertensive non-insulin-dependent diabetic patients had similar average values of both Na+-Li+ countertransport and Na+-K+ cotransport compared with nondiabetic controls. Within the group of diabetic patients, hypertensive patients did not exhibit any abnormalities in either of the sodium transport pathways studied. The possible implications of these findings are addressed.
Sodium responsiveness of central alpha 2-adrenergic receptors in spontaneously hypertensive rats.
Authors: Koepke J P , Jones S , DiBona G F
Published: June 2012

The responsiveness of central nervous system alpha 2-adrenergic receptors in the neural control of renal function was compared in conscious spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) on normal or high sodium intake (3-4 weeks of 1% NaCl for drinking). The responsiveness of central alpha 2-adrenergic receptors was determined by comparing among groups the dose-response curves for the effects of cumulative intracerebroventricular injections of guanabenz (5, 25, and 125 micrograms) on changes in mean arterial pressure, renal sympathetic nerve activity, and urinary sodium excretion. Guanabenz altered mean arterial pressure similarly in SHR on normal or high sodium intake and in WKY on normal or high sodium intake. High sodium intake shifted the guanabenz-renal sympathetic nerve activity and guanabenz-urinary sodium excretion dose-response curves to the left in SHR and to the right in WKY. The dose-response curves between SHR and WKY on normal sodium intake were similar. Surgical renal denervation or pretreatment with an alpha 2-adrenergic receptor antagonist (rauwolscine, 30 micrograms i.c.v.) attenuated the ability of guanabenz to inhibit renal sympathetic nerve activity or increase urinary sodium excretion in SHR and WKY on either normal or high sodium intake. We conclude that the responsiveness of central nervous system alpha 2-adrenergic receptors regarding the neural control of renal function is increased by high sodium intake in conscious SHR, but not in conscious normotensive WKY.
Effects of moderate diabetes on cardiac performance in spontaneously hypertensive and Wistar-Kyoto rats.
Authors: Yamamoto J , Nakai M
Published: June 2012

To assess the effects of imposition of moderate diabetes on in vivo cardiac performance in gradually proceeding hypertension, spontaneously hypertensive (SHR) and Wistar-Kyoto rats (WKY) were treated with streptozotocin (40 mg/kg) or vehicle at 8 weeks of age. Four and 20 weeks later, with the rats under ether anesthesia, peak cardiac output and stroke volume were measured during volume loading and peak left ventricular developed pressure and maximum rate of rise of pressure (dP/dtmax) were determined during aortic occlusion. Additionally, passive pressure-volume relations were obtained during saline infusion in potassium-arrested hearts, and the chamber stiffness constant was derived from one exponential function. There was a mortality of 16.1% in the diabetic SHR only. While basal and stressed cardiac performance was unchanged despite the already decreased mean arterial pressure and left ventricular weight at 4 weeks, the diabetic SHR revealed significant decreases in peak cardiac pumping indexes, peak left ventricular developed pressure, and dP/dtmax, with unchanged resting cardiac function, at 20 weeks. Changes seen in the diabetic WKY were reduced left ventricular weight at 4 weeks and reduced peak left ventricular dP/dtmax at 20 weeks. The chamber stiffness was unaltered with strain or diabetes. These data show that imposition of even moderate diabetes substantially influences the stress-loaded in vivo cardiac performance in the SHR, whereas it produces only minor changes in the WKY.
An impedance method for blood pressure measurement in awake rats without preheating.
Authors: Wen S F , Tremblay J M , Qu M H , Webster J G
Published: June 2012

The tail-cuff methods for measuring systolic blood pressure in the rat usually require preheating of the animal to obtain recordable pulse signals. To find a more sensitive method, we applied the principle of differentiated impedance (dZ/dt) to the tail-cuff measurement of systolic blood pressure. We obtained clear pulse signals from the tail in awake rats without preheating the animals, and the systolic blood pressure obtained by this method had an excellent correlation with the directly measured femoral artery pressure (correlation coefficient = 0.98). Heating the animals at 40 degrees C for 5 minutes increased systolic blood pressure by a mean of 6 mm Hg as compared with that determined at the ambient temperature of 21 to 24 degrees C. Mean systolic blood pressure in young female diabetic rats was 122 +/- 3 mm Hg, which was significantly higher than the 111 +/- 2 mm Hg of normal rats. It is concluded that the technique of electrical impedance as applied to the tail-cuff method is simple and highly sensitive and is suitable for measurement of tail systolic blood pressure in awake rats without preheating.
Endothelium-dependent and endothelium-independent vasodilation in resistance arteries from hypertensive rats.
Authors: Tesfamariam B , Halpern W
Published: June 2012

The endothelium-dependent and presumed endothelium-independent vasodilators acetylcholine and sodium nitroprusside, respectively, were used to characterize relaxation responses of mesenteric resistance arteries from stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto rats (WKY). Vessels were preconstricted using concentrations of norepinephrine or 5-hydroxytryptamine, which reduced their diameters by 50 to 60%. Relaxation responses to acetylcholine (10(-8) - 10(-7) M) were significantly smaller (p less than 0.05) in vessel segments from SHRSP, but the maximal relaxations at higher concentrations were the same in both strains. However, SHRSP vessels relaxed to a greater extent than did those of the WKY at all concentrations of sodium nitroprusside. Endothelium removal significantly enhanced sodium nitroprusside-induced dilations in both rat strains, and the dilations were significantly greater in segments from SHRSP in the concentration range of 3 X 10(-8) to 10(-6) M. The decreased relaxation to acetylcholine in resistance arteries from adult hypertensive rats compared with those from the normotensive strain suggests that functional alterations in the endothelium may play a role in hypertensive disease.