bluuebunny/crossref_metadata_2025 huggingface dataset:
Electrophysiologic Effects of Adenosine in Patients With Supraventricular Tachycardia
Authors: Glatter Kathryn A. , Cheng Jie , Dorostkar Parvin , Modin Gunnard , Talwar Sandeep , Al-Nimri Marwan , Lee Randall J. , Saxon Leslie A. , Lesh Michael D. , Scheinman Melvin M.
Published: June 2012

Background
—We correlated the electrophysiologic (EP) effects of adenosine with tachycardia mechanisms in patients with supraventricular tachycardias (SVT).

Methods and Results
—Adenosine was administered to 229 patients with SVTs during EP study: atrioventricular (AV) reentry (AVRT; n=59), typical atrioventricular node reentry (AVNRT; n=82), atypical AVNRT (n=13), permanent junctional reciprocating tachycardia (PJRT; n=12), atrial tachycardia (AT; n=53), and inappropriate sinus tachycardia (IST; n=10). There was no difference in incidence of tachycardia termination at the AV node in AVRT (85%) versus AVNRT (86%) after adenosine, but patients with AVRT showed increases in the ventriculoatrial (VA) intervals (13%) compared with typical AVNRT (0%),
P
<0.005. Changes in atrial, AV, or VA intervals after adenosine did not predict the mode of termination of long R-P tachycardias. For patients with AT, there was no correlation with location of the atrial focus and adenosine response. AV block after adenosine was only observed in AT patients (27%) or IST (30%). Patients with IST showed atrial cycle length increases after adenosine (
P
<0.05) with little change in activation sequence. The incidence of atrial fibrillation after adenosine was higher for those with AVRT (15%) compared with typical AVNRT (0%)
P
<0.001, or atypical AVNRT (0%) but similar to those with AT (11%) and PJRT (17%).

Conclusions
—The EP response to adenosine proved of limited value to identify the location of AT or SVT mechanisms. Features favoring AT were the presence of AV block or marked shortening of atrial cycle length before tachycardia suppression. Atrial fibrillation was more common after adenosine in patients with AVRT, PJRT, or AT. Patients with IST showed increases in cycle length with little change in atrial activation sequence after adenosine.
Arterial Flow Conditions Downregulate Thrombomodulin on Saphenous Vein Endothelium
Authors: Gosling Martin , Golledge Jonathan , Turner Robert J. , Powell Janet T.
Published: June 2012

Background
—The antithrombogenic properties of venous endothelium may be attenuated when vein is implanted in the arterial circulation. Such changes may facilitate thrombosis, which is the final common pathway for saphenous vein arterial bypass graft occlusion.

Methods and Results
—Using human saphenous vein in a validated ex vivo flow circuit, we investigated (1) the possibility that arterial flow conditions (mean pressure, 100 mm Hg, 90 cpm, ≈200 mL/min) alter the concentration of proteins involved in regulating thrombosis at the vessel wall and (2) the influence of ion channel blockade on such effects. Concentrations of thrombomodulin and tissue factor were quantified by Western blotting (ratio of von Willebrand factor staining) and immunohistochemistry (as a percentage of CD31-staining area). Thrombomodulin concentrations after 90 minutes of venous and arterial flow conditions were quantified by immunostaining (68.9±4.8% and 41.0±3.0% CD31, respectively;
P
<0.01) and by Western blotting (1.35±0.20 and 0.15±0.03 ratio of von Willebrand factor, respectively;
P
<0.01). The ability of endothelial cells to generate activated protein C also decreased from 62±14 to 19±10 ng · min
−1
· 1000 cells
−1
(
P
=0.01). The significant reduction in thrombomodulin was attenuated if calcium was removed from the perfusate but not by external vein stenting. Inclusion in the vein perfusate of drugs that reduce calcium entry (including Gd
3+
, to block stretch-activated ion channels, and nifedipine) abolished the reduction in thrombomodulin concentration observed after arterial flow conditions. In freshly excised vein, negligible concentrations of tissue factor were detected on the endothelium and concentrations did not increase after 90 minutes of arterial flow conditions, although the inclusion of nifedipine caused the immunostaining to increase from 3.0±0.4% to 8.5±0.7% CD31 (
P
<0.02).

Conclusions
—In saphenous vein endothelium exposed to arterial flow conditions, there is rapid downregulation of thrombomodulin, sufficient to limit protein C activation, by a calcium-dependent mechanism.
G20210A Mutation in Prothrombin Gene and Risk of Myocardial Infarction, Stroke, and Venous Thrombosis in a Large Cohort of US Men
Authors: Ridker Paul M. , Hennekens Charles H. , Miletich Joseph P.
Published: June 2012

Background
—A single base pair mutation in the prothrombin gene has recently been identified that is associated with increased prothrombin levels. Whether this mutation increases the risks of arterial and venous thrombosis among healthy individuals is controversial.

Methods and Results
—In a prospective cohort of 14 916 men, we determined the prevalence of the G20210A prothrombin gene variant in 833 men who subsequently developed myocardial infarction, stroke, or venous thrombosis (cases) and in 1774 age- and smoking status–matched men who remained free of thrombosis during a 10-year follow-up (control subjects). Gene sequencing was used to confirm mutation status in a subgroup of participants. Overall, carrier rates for the G20210A mutation were similar among case and control subjects; the relative risk of developing any thrombotic event in association with the 20210A allele was 1.05 (95% CI, 0.7 to 1.6;
P
=0.8). We observed no evidence of association between mutation and myocardial infarction (RR=0.8,
P
=0.4) or stroke (RR=1.1,
P
=0.8). For venous thrombosis, a modest nonsignificant increase in risk was observed (RR=1.7,
P
=0.08) that was smaller in magnitude than that associated with factor V Leiden (RR=3.0,
P
<0.001). Nine individuals carried both the prothrombin mutation and factor V Leiden (5 controls and 4 cases). One individual, a control subject, was homozygous for the prothrombin mutation.

Conclusions
—In a large cohort of US men, the G20210A prothrombin gene variant was not associated with increased risk of myocardial infarction or stroke. For venous thrombosis, risk estimates associated with the G20210A mutation were smaller in magnitude than risk estimates associated with factor V Leiden.
Selective Potentiation of Peripheral Chemoreflex Sensitivity in Obstructive Sleep Apnea
Authors: Narkiewicz Krzysztof , van de Borne Philippe J. H. , Pesek Catherine A. , Dyken Mark E. , Montano Nicola , Somers Virend K.
Published: June 2012

Background
—The chemoreflexes are an important mechanism for regulation of both breathing and autonomic cardiovascular function. Abnormalities in chemoreflex mechanisms may be implicated in increased cardiovascular stress in patients with obstructive sleep apnea (OSA). We tested the hypothesis that chemoreflex function is altered in patients with OSA.

Methods and Results
—We compared ventilatory, sympathetic, heart rate, and blood pressure responses to hypoxia, hypercapnia, and the cold pressor test in 16 untreated normotensive patients with OSA and 12 normal control subjects matched for age and body mass index. Baseline muscle sympathetic nerve activity (MSNA) was higher in the patients with OSA than in the control subjects (43±4 versus 21±3 bursts per minute;
P
<0.001). During hypoxia, patients with OSA had greater increases in minute ventilation (5.8±0.8 versus 3.2±0.7 L/min;
P
=0.02), heart rate (10±1 versus 7±1 bpm;
P
=0.03), and mean arterial pressure (7±2 versus 0±2 mm Hg;
P
=0.001) than control subjects. Despite higher ventilation and blood pressure (both of which inhibit sympathetic activity) in OSA patients, the MSNA increase during hypoxia was similar in OSA patients and control subjects. When the sympathetic-inhibitory influence of breathing was eliminated by apnea during hypoxia, the increase in MSNA in OSA patients (106±20%) was greater than in control subjects (52±23%;
P
=0.04). Prolongation of R-R interval with apnea during hypoxia was also greater in OSA patients (24±6%) than in control subjects (7±5%) (
P
=0.04). Autonomic, ventilatory, and blood pressure responses to hypercapnia and the cold pressor test in OSA patients were not different from those observed in control subjects.

Conclusions
—OSA is associated with a selective potentiation of autonomic, hemodynamic, and ventilatory responses to peripheral chemoreceptor activation by hypoxia.
Vasodilator Therapy for Primary Pulmonary Hypertension in Children
Authors: Barst Robyn J. , Maislin Greg , Fishman Alfred P.
Published: June 2012

Background
—This report presents 13 years of experience with vasodilator therapy for primary pulmonary hypertension (PPH) in children. Two eras were involved: between 1982 and 1987, oral calcium channel blockers were the only agents available for long-term therapy; after 1987, prostacyclin (PGI
2
) has been available for long-term intravenous use.

Methods and Results
—Seventy-four children underwent short-term vasodilator testing with intravenous PGI
2
. Those who manifested pulmonary vasodilation (“acute responders”) were treated with oral calcium channel blockers. Until 1987, “acute nonresponders” were treated in the same way as long as they had no serious side effects. When PGI
2
became available for long-term administration, all nonresponders, as well as those who failed to improve clinically and hemodynamically on calcium channel blockers, were treated with long-term PGI
2
. In the 31 responders, calcium channel blockers improved survival compared with the 43 nonresponders (
P
=0.0002). Survival was also better in 24 PGI
2
-treated nonresponders compared with 22 nonresponders for whom PGI
2
was unavailable (
P
=0.0005) as well as in all children who failed conventional therapy (n=31;
P
=0.002).

Conclusions
—Long-term vasodilator therapy improves survival in children with PPH. In acute responders, oral calcium channel blockers generally suffice. In both nonresponders to short-term testing and responders who fail to improve on calcium channel blockers, continuous intravenous infusion of PGI
2
improves survival.
Converting enzyme inhibition with an orally active compound in hypertensive man.
Authors: Bravo E L , Tarazi R C
Published: June 2012

The short-term cardiovascular and endocrine effects of an orally active angiotensin converting enzyme inhibitor, SQ14,225, were evaluated in 17 subjects with drug-resistant hypertension (10 with essential and seven with renovascular hypertension). On normal dietary sodium, SQ14,225 (after 3 days at average dose of 664 mg/day) reduced mean arterial pressure (MAP) significantly (from 141 +/- 4 to 122 +/- 4 mm Hg, (SE), p less than 0.001). However, only eight of the patients achieved blood pressures within the normotensive range. Of eight patients with residual hypertension, seven exhibited further decreases in MAP (from 132 +/- 4 to 108 +/- 6 mm Hg (SE), p less than 0.001) when dietary sodium was reduced to 10 mEq/day. No rebound hypertension was noted when treatment was temporarily discontinued for 3 days in 11 patients. The reductions in blood pressure were not associated with either orthostatic hypotension or interference with baroreceptor reflexes. The values of supine plasma renin activity (PRA) were not always predictive of blood pressure responsiveness to the drug. With treatment, plasma aldosterone concentrations (PAC) decreased modestly (values from 40 +/- 9 to 22 +/- 3 ng/dl (SE), p less than 0.05). The plasma concentrations of cortisol, norepinephrine and serum potassium were left unchanged during the period of studies. The present study has not defined the exact mechanism by which SQ14,225 lowered blood pressure. Nevertheless, it indicates that this agent may be a practical therapeutic adjunct in the treatment of certain subsets of the human hypertensive population. The lack of serious interference with cardioscular and humoral homeostasis adds to its attractiveness as a therapeutic agent.
Changes in plasma renin activity in cirrhosis: a reappraisal based on studies in 67 patients and "low-renin" cirrhosis.
Authors: Wilkinson S P , Smith I K , Williams R
Published: June 2012

The generally held views that plasma renin activity (PRA) is increased in cirrhosis and that this is secondary to reductions in the "effective" blood or extracellular fluid (ECF) volumes, consequent on the effects of portal hypertension, were re-examined in the present study. Measurements of PRA in 67 patients representing different clinical stages of cirrhosis showed that the mean value in 15 patients without ascites was significantly reduced. In 21 of 35 with ascites, PRA was either reduced or within the normal range. A low plasma renin substrate concentration was not the cause for the low PRA. These findings are not in keeping with the concepts of reduced "effective" blood or ECF volumes at least for the majority of patients at these stages of cirrhosis under the conditions of the present study. The only group showing a significantly increased PRA had evidence of renal impairment. In these 17 patients the underlying reduction in renal perfusion may have been the stimulus to the kidney that led to an increase to renin secretion.
Racial differences in pressure, volume and renin interrelationships in essential hypertension.
Authors: Chrysant S G , Danisa K , Kem D C , Dillard B L , Smith W J , Frohlich E D
Published: June 2012

The interrelationships of arterial pressure, plasma volume (PV), and plasma renin activity were studied in 152 consecutive male patients with uncomplicated essential hypertension. Of these, 22 (17 white and 5 black) subjects had normal plasma volumes and because of the small number were not included in the analysis of results. The remaining 130 (35 black and 95 white) patients were classified as having either expanded or contracted plasma volume. A higher percentage of black (43%) than white (21%) subjects were volume expanded (PV > 19 ml/cm) and a lower percentage of blacks (57%) than whites (79%) were volume contracted (PV < 17 ml/cm). There was not significant difference in mean arterial pressure and plasma renin activity between the volume expanded and contracted black patients. In contrast, the white patients with contracted plasma volume had significantly higher arterial pressures (p < 0.05) and plasma renin activity (p < 0.001) than those with expanded plasma volume. More blacks than whites had low plasma renin activity and did not manifest the inverse relationship of plasma renin activity to plasma volume as did the whites. These data confirm and extend previous observations that the relationship between plasma volume and plasma renin activity (PRA) in the male patient with essential hypertension seems to differ between the black and white race. Efforts to explain the low PRA in black patients might be best directed toward those patients with suppressed PRA and with contracted intravascular volume.
Blood pressure in childhood. The National Health Examination Survey.
Authors: Harlan W R , Cornoni-Huntley J , Leaverton P E
Published: June 2012

Data were analyzed from the U.S. Health Examination Survey (Cycle II) to determine relationships between blood pressure and other characteristics. This survey examined a national probability sample of children aged 6-11 years. Significant relationships were found for blood pressure and the following variables: chronological and skeletal age, skinfold thickness (adiposity) and other anthropometric measurements, pulse rate, and systolic murmurs. These relationships may be interpreted as indicating important relationships between blood pressure and growth, adiposity, and hemodynamic manifestations of cardiac output. Data from this representative population portray blood pressure relationships in childhood.
Blood pressure in adolescence. The United States Health Examination survey.
Authors: Cornoni-Huntley J , Harlan W R , Leaverton P E
Published: June 2012

A nationally representative sample of adolescents 12-17 years of age were examined in the U.S. Health Examination Survey and relationships between blood pressure and other variables were explored. During adolescence, blood pressure increases more rapidly in males than in females and only small racial differences are present. Weight has the strongest relationship to both systolic and diastolic pressure. Physiological maturation assessed by skeletal age and adiposity (skinfold thickness) are components of weight and each is also related to blood pressure. Although systolic murmurs are related to blood pressure at the time of examination, the murmurs are transitory and not predictive of future pressures. All factors were equally influential in each race-sex group. No significant relationships were found between geographic or demographic variables and blood pressure. These observations indicate the important relationships of physiological maturation and adiposity to adolescent blood pressure.
Hemodynamic responses to DOCA in young pigs.
Authors: Miller A W , Bohr D F , Schork A M , Terris J M
Published: June 2012

Hemodynamic variables were measured in 20 young pigs; thirteen received subcutaneous implantations of desoxycorticosterone acetate (DOCA) impregnated in Silastic strips, seven received implants of Silastic strips alone and served as controls. No salt was added to the standard diet of either group. Mean arterial pressure (MAP) rose in a regular pattern in the DOCA-treated pigs, reaching on the average a level significantly greater than that of the control group 48 hours after the implantation. Pressure continued to rise, reaching a plateau 38% above that of the preimplant value 2 weeks later. In some pigs the MAP elevation was caused by an increase in cardiac output (CO); in others it was caused by an increase in total peripheral resistance (TPR). An increase in central venous pressure occurred in many DOCA-treated pigs regardless of whether the increase in MAP was caused by an increase in CO or in TPR. The results indicate that it is arterial pressure per se that is the regulated variable in this model of mineralocorticoid hypertension. The regulating system, whether it resides in the kidney or in the central nervous system, elevates pressure by effecting increases in either CO or TPR.
Sympathetic nerve activity and blood pressure in normotensive backcross rats genetically related to the spontaneously hypertensive rat.
Authors: Judy W V , Watanabe A M , Murphy W R , Aprison B S , Yu P L
Published: June 2012

The genetic basis of hyperactivity of the sympathetic nervous system (SNA) in spontaneously hypertensive rats (SHR) was assessed by measuring SNA in animals derived from a backcross (BC) breeding program designed to isolate single gene differences causing changes in blood pressure. Selective breeding of the male hypertensive rats with inbred normotensive female Wistar/Lewis rats yielded progeny with a range of blood pressures, but whose group mean pressures were lower than the group mean pressures of the original SHR. Progressive generations had progressively lower group mean pressures. There was a positive correlation between SNA and mean arterial pressure in BC rats. These results indicate that the genetic defect in SHR may be abnormality in SNA, and the hypertension in these animals is a secondary result of this primary defect. Baroreceptor function was also assessed in SHR and in BC rats. In young (8 to 24 weeks old) SHR, baroreceptor function was similar to that in BC rats, whereas SNA was markedly increased. Only in older (24 to 40 weeks old) SHR was there an abnormality in the gain of baroreceptors. The development of hypertension in SHR therefore appears to be due to increased SNA resulting from a defect in the central nervous system. Changes in baroreceptor function are secondary to the hypertension and occur after the hypertension is established.
Resistance to mineralocorticoid-induced hypertensive vascular disease.
Authors: Sciotti V , Gallant S
Published: June 2012

To support our contention that the Wistar-Furth rat is resistant to mineralocorticoid hypertension, we assessed the effects of deoxycorticosterone (DOC) administration or renal artery stenosis on the development of hypertension in the Sprague-Dawley and Wistar-Furth rat strains. Weekly administration of mineralocorticoid in the form of DOC pivalate resulted in rapid, severe hypertensive cardiovascular disease in Sprague-Dawley rats. Within 5 weeks the mean conscious systolic blood pressures in steroid-treated and control rats were 186 +/- 4 and 118 +/- 5 mm Hg, respectively. In contrast, blood pressures of Wistar-Furth rats were only moderately elevated, even after 10 weeks of DOC pivalate administration (136 +/- 2 vs 116 +/- 2 mm Hg for controls). Furthermore, none of the steroid-treated Wistar-Furth animals exhibited cardiovascular lesions. In parallel studies, littermates of these rat strains were subjected to renal artery stenosis and blood pressures were determined weekly in conscious rats. Silver clip constriction of the left renal artery, in the presence of the contralateral kidney, resulted in a rapid, sustained elevation of blood pressure in both Sprague-Dawley and Wistar-Furth rat strains (177 +/- 4 and 176 +/- 5 mm Hg, respectively). Corticosteroid levels were also determined in DOC-treated Sprague-Dawley and Wistar-Furth rats. The regimen employed resulted in a 10-fold increase in DOC levels as compared with controls, and the levels achieved were comparable in both strains. Thus, the Wistar-Furth rat appears to be selectively resistant to mineralocorticoid hypertensive vascular disease and thus affords a model for studying mechanisms of steroid hypertension.
Calcium, the renin-aldosterone system, and the hypotensive response to nifedipine.
Authors: Resnick L M , Nicholson J P , Laragh J H
Published: June 2012

Ionic, hormonal, and blood pressure responses to a single oral dose of the calcium channel blocker nifedipine were assessed in 25 essential hypertensive subjects. When grouped according to their renin-sodium profile, low renin subjects had a greater hypotensive response to nifedipine (change in diastolic blood pressure -20.0 +/- 1.4 vs -6.4 +/- 1.0%; p less than 0.005) than did high renin hypertensive subjects. The initial level of serum ionized calcium predicted the blood pressure response to nifedipine (r = 0.70, p less than 0.001), as did the initial plasma renin activity (r = 0.65, p less than 0.005). Nifedipine induced a transient rise in serum ionized calcium (from 2.22 +/- 0.02 to 2.28 +/- 0.02 mEq/L; p less than 0.01), while plasma renin activity was consistently elevated compared with initial values at 30 (p less than 0.01), 60 (p less than 0.01), and 120 (p less than 0.05) minutes after drug administration. By comparison, plasma aldosterone levels did not rise and even declined at 30 (p less than 0.01), 60 (p less than 0.05), and 120 (p less than 0.05) minutes after nifedipine. These results suggest that low renin hypertension is more critically dependent on extracellular calcium than are higher renin forms and demonstrate that levels of serum ionized calcium, plasma renin activity, or both may predict the sensitivity of blood pressure to calcium channel blockade. Lastly, calcium may play a pivotal role in vivo in coupling renin stimulation to adrenal aldosterone responses.
Insulin and blood pressure during weight loss in obese adolescents.
Authors: Rocchini A P , Katch V , Schork A , Kelch R P
Published: June 2012

The role of insulin in the regulation of blood pressure was evaluated in 50 obese adolescents before and after a 20-week weight loss program. When compared with 10 nonobese adolescents, the obese subjects had significantly higher systolic, diastolic, and mean arterial pressures (p = 0.005), an elevated 24-hour urinary sodium excretion (p = 0.002), an elevated fasting insulin concentration (p = 0.001), and an abnormal insulin response to an oral glucose tolerance test (sum of the insulins at 0, 1, and 2 hours post-oral glucose load; p = 0.001). We also observed a significant correlation between systolic and diastolic blood pressure (age and sex normalized) and body weight (r = 0.57, p less than 0.01 and r = 0.7, p less than 0.01), fasting insulin (r = 0.49, p less than 0.01 and r = 0.54, p less than 0.01), and sum of insulins (r = 0.42, p less than 0.01 and r = 0.46, p less than 0.01). To study the effect of weight loss on the relationship between blood pressure and insulin, the obese subjects were randomly assigned to three groups: 15 to a diet and behavior change group, 18 to a diet, behavior change, and exercise group, and 17 to an obese control group. Compared with the obese control group, the two weight loss groups each experienced a significant decrease in insulin (p less than 0.01), sum of the insulins (p less than 0.01), and blood pressure (p less than 0.01). The decrease in blood pressure during the weight loss program significantly correlated with the change in both insulin and body weight.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of antiserum against alpha-rat atrial natriuretic peptide in anesthetized rats.
Authors: Sasaki A , Kida O , Kato J , Nakamura S , Kodama K , Miyata A , Kangawa K , Matsuo H , Tanaka K
Published: June 2012

Although synthetic atrial natriuretic peptide is known to increase urinary volume and sodium excretion and to reduce arterial blood pressure, the physiological role of endogenous atrial natriuretic peptide is still unclear. We investigated the effects of specific rabbit antiserum against alpha-rat atrial natriuretic peptide on hemodynamics, diuresis, and natriuresis in anesthetized rats. A significant rise in mean blood pressure lasted for about 60 minutes after intravenous administration of the antiserum, with the maximal increment being approximately 7%. Similarly, a significant increase in cardiac output was obtained 20 minutes after injection at an increment of approximately 11%. Heart rate, however, remained unchanged. On the other hand, significant reductions in urine output and urinary sodium and potassium excretion lasted for about 20 minutes after administration of the antiserum, with maximal decrements being 63%, 63%, and 60%, respectively. No significant effects on hemodynamics, diuresis, and natriuresis were observed following injection of normal rabbit serum. These results indicate that endogenous atrial natriuretic peptide has an important physiological role in the regulation of hemodynamics and water-electrolyte balance.
How can we diagnose coronary heart disease in hypertensive patients?
Authors: Prisant L M , Frank M J , Carr A A , von Dohlen T W , Abdulla A M
Published: June 2012

Chest pain is a common complaint among hypertensive patients. Hypertension and coronary heart disease each may present with symptoms and signs that are clinically indistinguishable. Noninvasive testing by routine exercise stress testing and stress radionuclide angiography are not reliably predictive of ischemia resulting from obstructive epicardial coronary artery disease and should be abandoned for that diagnostic purpose. Noninvasive thallium-201 myocardial perfusion imaging for this purpose may prove to be a valuable tool, avoiding the risk and expense of coronary arteriography. However, carefully performed prospective studies are not available. Because of the high prevalence of both diseases, a high priority must be given to obtaining these data and evaluating other noninvasive methods (especially positron emission tomography) if they appear promising.
Repetitive natriuresis and blood pressure. Long-term calcium entry blockade with isradipine.
Authors: Krusell L R , Jespersen L T , Schmitz A , Thomsen K , Pedersen O L
Published: June 2012

The long-term effects (3.5 months) of a new calcium entry blocker of the 1-4-dihydropyridine class, isradipine (PN 200-110), on renal hemodynamics and excretional parameters were investigated in 10 essential hypertensive subjects (World Health Organization Classes I and II). Blood pressure and renal vascular resistance fell significantly (p less than 0.001), and a slight increase in glomerular filtration rate and renal plasma flow was seen (p less than 0.05). Output of fluid from the proximal tubules, measured as clearance of lithium and uric acid, increased significantly (p less than 0.01 and p less than 0.05, respectively), and a compensatory increase in absolute reabsorption of sodium beyond the proximal tubular level accompanied by an increase in clearance of potassium was noted. A 40% increase in the resultant clearance of sodium (p less than 0.01) and an increase in diuresis (p less than 0.05) followed the morning dose of isradipine after 3.5 months of treatment. Changes in blood pressure were significantly correlated with changes in absolute proximal reabsorption of sodium (r = 0.81), excretion of sodium (r = -0.64), and diuresis (r = -0.80). Thus, the natriuretic properties of calcium entry blockers may be more important for the long-term antihypertensive effect than the vasodilator effect per se. A model for renal sodium handling following treatment with calcium entry blockers was proposed. Although a causal relationship is not implied, isradipine induced a sustained, repetitive postdose effect on proximal fluid output, net natriuresis, and diuresis, that was intimately related to the long-term blood pressure-regulating response.
Glucocorticoids modulate vascular reactivity in the rat.
Authors: Grünfeld J P , Eloy L
Published: June 2012

To clarify the role of endogenous glucocorticoids in the regulation of blood pressure, the cardiovascular effects of RU 486, a steroid derivative with antiglucocorticoid properties, were investigated in Wistar rats. Pressor responses to angiotensin II (Ang II), norepinephrine, and vasopressin were studied in normal conscious rats before and after administration of RU 486. At 20 mg/kg/day, RU 486 significantly blunted pressor responses to Ang II and norepinephrine, whereas those to vasopressin were not greatly affected. At a lower dose, RU 486 did not alter pressor responses; at a higher dose, it augmented them, probably through its agonistic glucocorticoid effect. At 20 mg/kg/day, RU 486 antagonized the enhancing effect of a glucocorticoid agonist on pressor responses to Ang II, norepinephrine, and vasopressin. Cardiac output and renal blood flow were measured in anesthetized rats by the microsphere method. RU 486 at 20 mg/kg/day did not alter basal cardiac output and renal blood flow. RU 486 pretreatment attenuated pressor responses to Ang II and norepinephrine but did not alter cardiac output. It significantly blunted the decrease in renal blood flow and the increase in renal vascular resistance induced by Ang II. In rats fed a low sodium diet (where the pressor systems are stimulated), administration of RU 486 (20 mg/kg/day for 5 days) decreased total peripheral vascular resistance by 29% and mean blood pressure by 20 mm Hg. This effect was unrelated to any antimineralocorticoid activity of the compound, as shown by unchanged urinary sodium excretion, sodium balance, and plasma renin concentration. In contrast, it was due to the antiglucocorticoid activity, as shown by restoration of mean blood pressure by corticosterone, the major glucocorticoid in rats. Renal vascular resistance decreased during RU 486 administration in anesthetized (-25%) and unanesthetized (-19%) rats. Glomerular filtration rate, estimated from inulin clearance in conscious rats, did not change significantly. In conclusion, the present results suggest that endogenous glucocorticoids increase vascular reactivity and therefore contribute to blood pressure regulation. They also participate in the control of renal hemodynamics. This effect is most apparent in salt-restricted rats. The vascular action of glucocorticoids was unmasked by the administration of the antiglucocorticoid compound RU 486.
Sodium transport kinetics in erythrocytes from spontaneously hypertensive rats.
Authors: Rosati C , Meyer P , Garay R
Published: June 2012

Rat erythrocytes with five different amounts of Na+ content have been prepared by using a new, nondetrimental Na+-loading method (net NaHPO4-influx through the anion carrier). This method allowed the determination of 1) maximal translocation rates and apparent dissociation constants for internal Na+ of the Na+-K+ pump, outward Na+-K+ cotransport, and Na+-Li+ countertransport and 2) rate constants of Na+ leak in erythrocytes from spontaneously hypertensive rats of the Okamoto strain and Wistar-Kyoto normotensive controls aged 2 to 26 weeks. Two major abnormalities were found in erythrocytes from spontaneously hypertensive rats: 1) a decreased cotransport affinity for internal Na+, which was constantly observed from 2 to 26 weeks of age (mean intracellular Na+ content for half-maximal stimulation of outward Na+-K+ cotransport = 33.1 +/- 7.0 [SD] mmol/L cells in spontaneously hypertensive rats vs 16.7 +/- 4.7 mmol/L cells in Wistar-Kyoto rats; p less than 0.001), and 2) a decreased maximal pump rate in adult (15- to 26-week-old) spontaneously hypertensive as compared with that for age-matched Wistar-Kyoto rats (9-37 vs 34-70 mmol/L cells/hr). Therefore, the low cotransport affinity for internal Na+ appears to be a stable, possibly genetic defect of spontaneously hypertensive rats. Conversely, the decreased maximal pump rate may be a secondary event, possibly reflecting the appearance of endogenous pump inhibitors in the plasma of adult spontaneously hypertensive rats.
Serotoninergic mechanisms in hypertension. Focus on the effects of ketanserin.
Authors: Vanhoutte P , Amery A , Birkenhäger W , Breckenridge A , Bühler F , Distler A , Dormandy J , Doyle A , Frohlich E , Hansson L
Published: June 2012

Aggregating platelets release serotonin, which induces contraction of most vascular smooth muscle by activation of S2-serotoninergic receptors. Serotonin released in the circulation may contribute to the increase in peripheral resistance of hypertension as the responsiveness of blood vessels from hypertensive animals and humans to the vasoconstrictor action of the monoamine is augmented. The data obtained with the new antihypertensive agent ketanserin may favor that interpretation. Ketanserin is a selective S2-serotoninergic antagonist with additional alpha 1-adrenergic blocking properties. In humans, it has a terminal half-life of 12 to 25 hours and is eliminated predominantly by the liver. The hemodynamic profile of ketanserin is that of a vasodilator drug with actions on both resistance and capacitance vessels. On short-term intravenous administration, it lowers blood pressure in hypertensive patients with minimal reflex changes in cardiovascular function. When given orally long term to hypertensive patients, ketanserin causes a sustained reduction in arterial blood pressure, comparable to that obtained with either beta-adrenergic blockers or diuretics. Several studies have shown a greater efficacy in older (greater than 60 years of age) than in younger patients independent of starting pressure. Side effects mainly consist of dizziness, somnolence, and dry mouth, but they are usually not severe. The mechanism underlying the antihypertensive effect of ketanserin is unclear. It cannot be attributed to either S2-serotoninergic or alpha 1-adrenergic blockade alone, but an interaction between the two effects appears to be required.
Renal glomerular atrial natriuretic factor receptors in one-kidney, one clip rats.
Authors: Garcia R , Gauquelin G , Cantin M , Schiffrin E L
Published: June 2012

One-kidney, one clip (1K1C) hypertension is often associated with an expanded plasma volume and (once the arterial clip is removed) with natriuresis. Blood pressure (BP), atrial and plasma concentrations of atrial natriuretic factor (ANF), hematocrit, and renal glomerular ANF receptors were therefore studied in 1K1C rats and in their normotensive uninephrectomized controls before and after unclipping. Six hours after removal of the clip, BP was normal in the 1K1C group and plasma ANF presented a sharp decline but was still significantly higher than in the normotensive controls, with a slight difference being evident 24 hours after unclipping. Hematocrit was lower in the 1K1C rats than in their control counterparts, but this difference tended to disappear once the clip was removed, indicating a contraction of plasma volume in these unclipped 1K1C animals. The renal glomerular ANF receptor population was markedly smaller in 1K1C rats than in the uninephrectomized controls but showed a twofold increase in number and affinity 24 hours after unclipping. It is concluded that the up-regulation and enhanced affinity of glomerular ANF receptors (probably secondary to the decrease in plasma levels of ANF) may contribute to the natriuresis reported in hypertensive 1K1C animals on removal of the arterial clip.
Effect of a kinin antagonist on the acute antihypertensive activity of enalaprilat in severe hypertension.
Authors: Carbonell L F , Carretero O A , Stewart J M , Scicli A G
Published: June 2012

The purpose of this study was to assess the role of kinins in the acute antihypertensive effect of the converting enzyme inhibitor (CEI) enalaprilat in rats with severe hypertension induced by aortic ligation between both renal arteries. For this study, we used a bradykinin analogue, D-Arg-Arg-Pro-Hyp-Gly-Thi-Ser-DPhe-Thi-Arg-TFA, with in vivo antagonistic properties. Hypertensive rats were infused intra-aortically for 15 minutes with either saline (30 microliters/min) or the kinin antagonist (40 micrograms/kg/min). Five minutes after the infusion was begun, a bolus injection of enalaprilat (60 micrograms/kg) was given. The blood pressure of the saline-infused animals decreased 48 +/- 6 mm Hg (from 180 +/- 7 to 132 +/- 7 mm Hg), while that of the rats treated with the antagonist decreased only 21 +/- 4 mm Hg (from 175 +/- 3 to 154 +/- 3 mm Hg). The difference between both decrements was significant (p less than 0.01). In another group of hypertensive animals (n = 9), we measured kinin concentration in plasma from arterial blood before and after administration of CEI (41 +/- 10 vs 68 +/- 20 pg/ml, respectively; NS). These results are consistent with the hypothesis that kinins play a role in the acute antihypertensive effect of CEIs in rats with severe hypertension. However, since arterial blood kinin concentrations were not increased significantly after CEI administration, the effect of the CEI may be due to an increase in tissue kinins, which could act as autacoids regulating vascular resistance.
Development of hypertension after correction of primary hyperparathyroidism.
Authors: Cirillo M , Strazzullo P , Galletti F , Mancini M
Published: June 2012

A statistical association between hypertension and hyperparathyroidism has been repeatedly reported, but the underlying pathogenetic mechanism has not been elucidated. A 51-year-old woman was hospitalized because of increasing motor disability caused by multiple bone and muscle aches with generalized weakness. She was found to have marked hypercalcemia and hypophosphatemia, increased parathyroid hormone secretion, but normal renal function and blood pressure level. After the identification and removal of a single parathyroid adenoma, the calcium/phosphate metabolism normalized in a relatively short time during which, however, hypertension developed in the absence of any other endocrine or renal dysfunction. A positive, highly significant relationship was observed between the progressive rise in blood pressure and the gradual increase in serum phosphate concentration occurring after the operation, suggesting that, in the hyperparathyroid phase, an underlying trend to hypertension could have been masked by the phosphate depletion, probably through its effects on cardiac and vascular smooth muscle function.
Location and regulation of rat angiotensinogen messenger RNA.
Authors: Cassis L A , Saye J , Peach M J
Published: June 2012

The presence of angiotensinogen messenger RNA (mRNA) was detected in rat vascular and adipose tissue. Angiotensinogen mRNA in rat aorta was localized in the adventitia and surrounding adipose tissue, and not in the vascular smooth muscle. Freshly dispersed and cultured endothelial and aortic smooth muscle cells did not contain detectable amounts of angiotensinogen mRNA. In addition to periaortic adipose tissue, angiotensinogen mRNA was present in other fat depots of both brown and white types. To examine regulation of angiotensinogen gene expression, Sprague-Dawley rats were treated with angiotensin converting enzyme inhibitor or underwent bilateral nephrectomy. Relative levels of angiotensinogen mRNA in brown adipose tissues increased dramatically by 48 hours after bilateral nephrectomy. However, only one source of brown adipose tissue showed increased angiotensinogen mRNA levels after animals were treated for 5 days with converting enzyme inhibitor. In addition, angiotensinogen was released into the medium from incubated adipose tissues with levels increasing over a 2-hour period. These results demonstrate that angiotensinogen is synthesized by adipose tissue in the rat and may play a role in the function of this tissue.
Role of the nucleus ambiguus in the regulation of heart rate and arterial pressure.
Authors: Machado B H , Brody M J
Published: June 2012

The present study examined the effect of lesion of cell bodies in the nucleus ambiguus area on the development of neurogenic hypertension and further explored the cardiovascular responses produced by chemical and electrical stimulation of the nucleus ambiguus and the neighboring C1 region. Three days after chemical lesion of the nucleus ambiguus with kainic acid, arterial pressure and heart rate were unchanged; however, subsequent sinoaortic deafferentation produced a significantly greater increase of arterial pressure (157 +/- 7 vs 132 +/- 5 mm Hg) and heart rate (436 +/- 10 vs 374 +/- 10 beats/min) compared with those produced by sham lesion. Glutamate injected into the nucleus ambiguus increased arterial pressure and heart rate at 20 nmol/100 nl and decreased heart rate at 50 nmol/100 nl. Glutamate injected into the C1 area increased arterial pressure and heart rate at both doses. Gamma-Aminobutyric acid at 50 nmol/100 nl produced bradycardia and a fall in arterial pressure when injected into both the nucleus ambiguus and C1 area. The heart rate responses to gamma-aminobutyric acid and glutamate were attenuated in sinoaortic-deafferentated rats. The nucleus ambiguus and the C1 region were mapped using electrical stimulation with microelectrodes. All points stimulated in three anteroposterior sections in the nucleus ambiguus and the C1 area produced increases in arterial pressure, whereas bradycardia was restricted to the middle of three lateral coordinates associated with the center of the nucleus ambiguus and the C1 area ventral to the nucleus ambiguus.(ABSTRACT TRUNCATED AT 250 WORDS)
High potassium diet augments endothelium-dependent relaxations in the Dahl rat.
Authors: Raij L , Lüscher T F , Vanhoutte P M
Published: June 2012

Endothelium-dependent relaxations are reduced in hypertensive rats. High dietary potassium supplementation reduces the incidence of strokes in Dahl rats independently of blood pressure, thereby suggesting a direct protective effect of the diet. Endothelium-dependent relaxations and aortic vascular architecture were studied in Dahl salt-sensitive rats fed 8% NaCl, 0.1% NaCl, or 8% NaCl plus 3.6% potassium citrate for 8 weeks. Rats fed 8% NaCl or 8% NaCl plus 3.6% potassium citrate became hypertensive, while those fed 0.1% NaCl did not. Aortic rings with and without endothelium were suspended in organ chambers filled with physiological salt solution (37 degrees C) and aerated with 95% O2, 5% CO2. In rings contracted with norepinephrine, acetylcholine and adenosine 5'-diphosphate caused endothelium-dependent relaxations that were significantly reduced in rats fed 8% NaCl as compared with those fed 0.1% NaCl. Potassium supplementation (8% NaCl/3.6% potassium citrate) significantly enhanced relaxations to acetylcholine in salt-sensitive rats, while those to adenosine 5'-diphosphate and thrombin were either minimally affected or unchanged. Relaxations to sodium nitroprusside were similar in rats with or without potassium supplementation. Hypertension significantly increased aortic medial and intimal thickness. Dietary potassium had no significant effect on the vascular architecture. These results suggest that high potassium diet enhances endothelium-dependent relaxations in Dahl rats at least in part independently of changes in blood pressure. Thus, potassium may be important for its protective effect against stroke and renal damage in this animal model of hypertension.
Relationship of serum sodium, potassium, calcium, and phosphorus with blood pressure. Belgian Interuniversity Research on Nutrition and Health.
Authors: Kesteloot H , Joossens J V
Published: June 2012

During an epidemiological survey on the relationship between diet and cardiovascular risk factors, serum sodium, potassium, calcium, phosphorus, and total protein were measured in 4167 men and 3891 women with a mean age of 49 years. Several consistent and highly significant correlations were found between serum cation and phosphorus levels and blood pressure. The analysis was performed separately in the total group and in the group not receiving treatment for hypertension. A highly significant negative correlation existed between serum sodium and both systolic and diastolic blood pressure. Serum potassium correlated negatively with blood pressure only in men. Serum phosphorus correlated negatively in men and women with systolic blood pressure. Serum calcium correlated positively with systolic and diastolic blood pressure in men, but only with diastolic blood pressure in women. All these correlations were independent of serum total protein. A significant negative correlation between serum phosphorus and heart rate and a significant positive correlation between the serum calcium/phosphorus ratio and heart rate were demonstrated.
Angiotensin-mediated renin suppression is altered in non-modulating hypertension.
Authors: Seely E W , Moore T J , Rogacz S , Gordon M S , Gleason R E , Hollenberg N K , Williams G H
Published: June 2012

Plasma renin activity (PRA) suppression by angiotensin II (Ang II), the "short feedback loop," has been shown to be blunted in essential hypertension. Non-modulators comprise 50% of normal- and high-renin essential hypertensive individuals and are defined by their abnormal adrenal and renal responses to infused Ang II. This study sought to determine if the abnormal Ang II suppression of PRA in essential hypertension is specific to non-modulators. We measured PRA suppression during infusion of Ang II in 22 normotensive and 32 hypertensive (16 modulators and 16 non-modulators) subjects. A significant correlation between basal PRA and the fall in PRA in response to Ang II infusion was seen in the normotensives (r = -0.934, p less than 0.001) and modulators (r = -0.831, p less than 0.001) but not in the non-modulators (r = -0.275, p = 0.304). However, after 3 days of converting enzyme inhibition therapy, the correlation between basal PRA and decrement in PRA was significant in the non-modulators (r = -0.762, p less than 0.01). Thus, the abnormal PRA suppression documented previously in hypertensive individuals is a defect specific to non-modulators and is corrected with converting enzyme inhibition therapy.