bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of the sympathetic nervous system in blood pressure maintenance and in the antihypertensive effects of calcium antagonists in spontaneously hypertensive rats.
Authors: Lefèvre-Borg F , Mathias O , Cavero I
Published: June 2012

In conscious spontaneously hypertensive rats (SHR), 2, 3, 6, 9, 12, and 16 months of age, the blockade of autonomic ganglia (with chlorisondamine) or postjunctional alpha 1-adrenergic receptors (with prazosin) or the depletion of peripheral norepinephrine stores (with syrosingopine), in contrast to the blockade of alpha 2-adrenergic receptors (with yohimbine, rauwolscine), produced a sustained decrease in the directly measured mean tail artery blood pressure. In 3- to 9-month-old SHR, the fall in blood pressure after prazosin pretreatment was significantly smaller than that after chlorisondamine or syrosingopine pretreatment. In ganglion-blocked SHR, prazosin decreased blood pressure only when this parameter had been elevated by an intra-arterial infusion of epinephrine or norepinephrine. In contrast, under the same experimental conditions, yohimbine or rauwolscine administration failed to modify the pressor effects of either phenylephrine or epinephrine but partially reduced those of norepinephrine and, unlike prazosin, strongly antagonized those of B-HT 920. In either intact or ganglion-blocked SHR, a 30-minute intra-arterial infusion of diltiazem at 100.0, but not 25.0, micrograms/kg/min significantly decreased baseline mean tail artery blood pressure. In ganglion-blocked SHR, the smaller dose of diltiazem antagonized by 40 and 80% the pressor effects of norepinephrine and B-HT 920, respectively, but failed to change the vasoconstrictor responses of phenylephrine, epinephrine, or vasopressin, which were, however, reduced by the higher dose of diltiazem. These results indicate that, in conscious adult SHR, norepinephrine released by peripheral sympathetic nervous terminals and humorally borne epinephrine stimulate almost exclusively post-junctional alpha 1-adrenergic receptors. The latter findings may account for the lack of blood pressure-lowering effects of the studied calcium antagonists at doses that effectively antagonize alpha 2-adrenergic receptor-mediated vasoconstriction in conscious SHR.
Effect of atrial natriuretic factor on calcium fluxes in adrenal glomerulosa cells.
Authors: Takagi M , Takagi M , Franco-Saenz R , Shier D , Mulrow P J
Published: June 2012

We studied the effect of atrial natriuretic factor (ANF) on calcium influx and efflux in rat adrenal glomerulosa cells stimulated by angiotensin II (Ang II) or potassium ion, and observed how ANF inhibits the initial and sustained phases of the aldosterone response to Ang II or K+ using a superfusion system of dispersed adrenal glomerulosa cells. K+ (8 mM) significantly increased Ca2+ influx rate compared with basal rate (0.91 +/- 0.10 vs 0.42 +/- 0.04 nmol/min/10(6) cells; p less than 0.01). ANF (10(-8) M) did not inhibit the K+-induced increase in Ca2+ influx rate (0.99 +/- 0.18 nmol/min/10(6) cells). Ang II (10(-9) and 10(-8) M) stimulated Ca2+ influx rate (10(-9) M Ang II, 0.62 +/- 0.02; 10(-8) M Ang II, 0.71 +/- 0.09 vs basal, 0.44 +/- 0.03 nmol/min/10(6) cells; p less than 0.05), while ANF (10(-8) M) did not change the Ca2+ influx rate increased by Ang II (ANF + 10(-9) M Ang II, 0.62 +/- 0.06; ANF + 10(-8) M Ang II, 0.69 +/- 0.14 nmol/min/10(6) cells). In the Ca2+ efflux study ANF (10(-8) M) was perfused through the cells 10 minutes before the start of perfusion with Ang II (10(-9) M) or K+ (12 mM).(ABSTRACT TRUNCATED AT 250 WORDS)
Is there a relationship between ambulatory intra-arterial blood pressure and left ventricular function?
Authors: Heber M E , Brigden G S , Prince H , Lahiri A , Raftery E B
Published: June 2012

The relationship between ambulatory intra-arterial blood pressure and left ventricular ejection fraction was examined in a group of 23 untreated hypertensive subjects who underwent concurrent radionuclide ventriculography. All patients had a normal ejection fraction at rest (range, 50-80%), and no significant correlation was found between blood pressure and resting ejection fraction. Sixty-one percent of patients failed to increase their ejection fraction by 5% on exercise; the mean daytime systolic pressure (168 +/- 15 mm Hg) was lower in this group than in those who had a normal exercise response (188 +/- 17 mm Hg; p less than 0.005). Thirty percent of patients had left ventricular hypertrophy based on electrocardiographic criteria; this group had a higher mean blood pressure (189 +/- 20 mm Hg) than the remainder (170 +/- 15 mm Hg; p less than 0.05). A closer correlation was demonstrated between blood pressure and ejection fraction response to exercise in the group with left ventricular hypertrophy (r = 0.8) than in the group without hypertrophy (r = 0.3). These results failed to demonstrate a linear relationship between blood pressure and ejection fraction. However, a relationship between the height of blood pressure and the development of left ventricular hypertrophy was shown, and myocardial response to exercise was increased in patients with left ventricular hypertrophy.
Effects of beta-blockade and exercise on cardiovascular and cognitive functioning.
Authors: Madden D J , Blumenthal J A , Ekelund L G
Published: June 2012

Twenty-four men with mild essential hypertension were assigned randomly to receive propranolol (n = 9), atenolol (n = 7), or a placebo (n = 8). All subjects participated in a 12-week study and provided physiological and behavioral data four times during the study: after a medication-free baseline period (Session 1); after 2 weeks of medication, without exercise (Session 2); after 8 weeks of continued medication while participating in a program of aerobic exercise (Session 3); and after 2 weeks of maintenance exercise without medication (Session 4). Subjects' maximal oxygen uptake increased significantly between Sessions 2 and 3, and the magnitude of this increase did not vary across the drug groups. Subjects' resting heart rates varied as a function of the presence of beta-blocking medication, but there was in addition a reduction attributable to exercise training that did not vary across the drug groups. The decrease in blood pressure associated with beta-blockade (Session 2) was not decreased any further by exercise training (Session 3). Despite an increase in blood pressure following the withdrawal of active medication (Session 4), blood pressure remained significantly lower compared with the Session 1 baseline level. Performance in a reaction-time test of short-term memory functioning improved slightly for all three groups between Sessions 1 and 2 and remained constant thereafter.(ABSTRACT TRUNCATED AT 250 WORDS)
Sodium depletion increases platelet and plasma catecholamines in hypertensive men.
Authors: Kjeldsen S E , Westheim A , Lande K , Gjesdal K , Leren P , Enger E , Eide I K
Published: June 2012

The catecholamine content in blood platelets is considerably higher than that in plasma, and platelet catecholamines must be taken up from plasma, since blood platelets lack enzymes for catecholamine synthesis. However, it is unknown whether platelets take up and store catecholamines during physiological in vivo increments in plasma catecholamines. Previously untreated 50-year-old men (n = 17) with mild to moderate essential hypertension were given a low sodium diet for 2 weeks. Urinary excretion of sodium decreased from 201 +/- 11 (SE) to 24 +/- 5 and 19 +/- 4 mmol/24 hr after 1 and 2 weeks, respectively. During the first week, the blood platelet concentration of norepinephrine increased from 27.2 +/- 2.9 to 39.6 +/- 4.7 pg/mg (p less than 0.005) and venous plasma norepinephrine increased from 3.7 +/- 0.4 to 5.6 +/- 0.5 pg/ml (p less than 0.005), and venous plasma dopamine increased from 26 +/- 4 to 41 +/- 5 pg/ml (p less than 0.05). During the second week, both plasma and platelet norepinephrine and dopamine remained elevated. Platelet epinephrine showed a small increase from baseline to the second week (p less than 0.05), but no concomitant increase in plasma epinephrine occurred. Thus, sodium depletion increases both platelet and plasma catecholamines and blood platelets may take up catecholamines in vivo. Platelet catecholamine content may be an integrated measure of plasma catecholamine concentrations during variations caused by sodium depletion.
Atrial natriuretic factor in mild to moderate chronic renal failure.
Authors: Suda S , Weidmann P , Saxenhofer H , Cottier C , Shaw S G , Ferrier C
Published: June 2012

The relationship between kidney function and plasma immunoreactive atrial natriuretic factor (irANF) levels as well as the effects of synthetic human ANF-(99-126) were investigated in 13 patients with mild to moderate chronic renal failure. Under basal conditions, glomerular filtration rate averaged 39 +/- 5 (SEM) ml/min/1.73 m2 and blood pressure (BP) averaged 166/107 +/- 7/2 mm Hg; 12 patients were hypertensive. Plasma irANF levels were significantly increased (98 +/- 16 vs 42 +/- 4 pg/ml in healthy control subjects; p less than 0.001) and correlated (p less than 0.05-0.005) inversely with hematocrit (r = -0.65) and positively with systolic BP (r = 0.75) or fractional sodium excretion (r = 0.75). Human ANF-(99-126) infusion for 45 minutes at 0.034 microgram/kg/min augmented (p less than 0.05-0.01) diuresis and urinary sodium, chloride, calcium, phosphate, and magnesium excretion. During the subsequent 45 minutes of human ANF-(99-126) infusion at a rate of 0.077 microgram/kg/min, diuresis and electrolyte excretion remained elevated (p less than 0.05-0.01). Glomerular filtration rate and effective renal plasma flow were not significantly modified, but filtration fraction rose progressively (p less than 0.01). Human ANF-(99-126) infusion decreased BP (p less than 0.05-0.01), produced hemoconcentration (hematocrit + 7%; p less than 0.01) without negative body fluid balance, and increased (p less than 0.01-0.001) plasma norepinephrine, insulin, and serum free fatty acids; plasma aldosterone and renin activity were unaltered during but rose after cessation of human ANF-(99-126) infusion.(ABSTRACT TRUNCATED AT 250 WORDS)
Role of angiotensin II in renal prostaglandin E2 production after furosemide administration.
Authors: Fujimura A , Ebihara A
Published: June 2012

The role of plasma angiotensin II (Ang II) in furosemide-stimulated renal prostaglandin E2 (PGE2) production was evaluated in eight healthy subjects. Urine was collected for 60 minutes after furosemide administration (20 mg i.v.) with or without captopril pretreatment, and urinary excretion of PGE2, sodium, and furosemide was determined. Plasma renin activity (PRA) and Ang II were also measured before and 60 minutes after furosemide administration. Urinary PGE2 excretion, PRA, and Ang II increased after furosemide administration without captopril pretreatment, and there was a significant correlation between the increment in Ang II and that in urinary PGE2 excretion. Urinary PGE2 excretion and Ang II did not increase after furosemide administration with captopril pretreatment. Urine volume and urinary excretion of sodium and furosemide were not influenced by captopril pretreatment. These results suggest that Ang II may play an important role in furosemide-stimulated PGE2 production.
Atrial natriuretic factor release by angiotensin II in the conscious rat.
Authors: Lachance D , Garcia R
Published: June 2012

Since it was previously reported that atrial natriuretic factor (ANF) may exert an inhibitory effect on renin release, the existence of an Angiotensin II (Ang II)-ANF feedback mechanism was investigated. Male rats were infused intraperitoneally for 7 days with either saline, a nonpressor dose of Ang II (200 ng/kg/min), or a pressor dose (800 ng/kg/min) of Ang II. Systolic blood pressure, plasma ANF, 24-hour urinary sodium excretion, urine volume, and water intake were measured. A significant increase in plasma ANF was observed in the group with a pressor response (blood pressure rose from 89.0 +/- 3.9 to 136.7 +/- 11.4 mm Hg; ANF rose from 36.8 +/- 4.9 to 92.7 +/- 17.7 pg/ml). There was no significant time effect on 24-hour sodium excretion, urine volume, and water intake in both Ang II-infused groups. In a second set of experiments, male rats were infused intravenously for 60 minutes with either saline, a nonpressor dose of Ang II (16 ng/kg/min), or a pressor dose (800 ng/kg/min) of Ang II. Left ventricular end-diastolic pressure, right atrial pressure, and mean arterial pressure were monitored. There was a significant increase in plasma ANF and left ventricular end-diastolic pressure only with the pressor dose (blood pressure rose from 85.0 +/- 6.1 to 140.0 +/- 5.5 mm Hg; ANF rose from 22.6 +/- 6.0 to 108.3 +/- 47.7 pg/ml; left ventricular end-diastolic pressure rose from 5.3 +/- 5.7 to 20.8 +/- 7.9 mm Hg). No significant modification of right atrial pressure was recorded.(ABSTRACT TRUNCATED AT 250 WORDS)
Renal effects of amino acid infusions in patients with panhypopituitarism.
Authors: Ruilope L , Rodicio J , Miranda B , Garcia Robles R , Sancho-Rof J , Romero J C
Published: June 2012

Strong evidence indicates that a high protein diet accelerates end-stage renal disease by increasing glomerular capillary pressure subsequent to renal vasodilatation. The mechanisms underlying this vasodilatation remain undefined, but they have been suspected to be mediated by a pituitary factor. To test this possibility, we measured changes in renal plasma flow and glomerular filtration rate induced by an intravenous infusion of a solution of amino acids in two patients with panhypopituitarism. These patients exhibited changes in renal hemodynamics comparable to those recorded in nine healthy volunteers. The results do not support involvement of the pituitary gland in the acute renal response to amino acids.
Activated endothelial cells in culture suppress baroreceptors in the carotid sinus of dog.
Authors: Chapleau M W , Hajduczok G , Shasby D M , Abboud F M
Published: June 2012

Vascular stretch increases the activity of arterial baroreceptors along with the production and release of substances from the endothelium. We hypothesized that endothelial factors modulate the sensitivity of baroreceptors during increases in arterial pressure. Baroreceptor activity was recorded from single fibers innervating the isolated carotid sinus of dogs anesthetized with chloralose after removal of the endothelium (balloon denudation) and after replacing into the denuded sinus bovine aortic endothelial cells cultured on microcarrier beads. The endothelial cells were activated with either the calcium ionophore A23187 (2 microM) or bradykinin (10 microM). The threshold pressure (n = 7) determined with a slow ramp increase in static pressure averaged 73 +/- 7 (SEM) mm Hg during exposure to naked beads and was increased significantly (96 +/- 18 mm Hg; p less than 0.05) during exposure to endothelial cell cultures. During stepwise increases in pressure, activity (n = 6) averaged 14 +/- 5, 40 +/- 8, and 54 +/- 8 spikes/sec at 75, 125, and 175 mm Hg during exposure to naked beads and decreased significantly to 2 +/- 2, 30 +/- 11, and 35 +/- 12 spikes/sec at equivalent pressures during exposure to the cell cultures. The activity was restored after replacement of the cell cultures with naked beads. The suppressed activity was not caused by changes in carotid sinus diameter or strain (sonomicrometers) or by the chemical activators that were also added to the naked beads. The results indicate that chemically activated endothelial cells release an inhibitory factor that suppresses baroreceptor activity.
Effects of intravenously administered beta-human atrial natriuretic polypeptide in humans.
Authors: Itoh H , Nakao K , Mukoyama M , Shiono S , Morii N , Sugawara A , Yamada T , Saito Y , Arai H , Hosoda K
Published: June 2012

beta-Human atrial natriuretic polypeptide (beta-hANP) is an antiparallel dimer of alpha-human ANP (alpha-hANP) that was isolated from human atria. Using synthetic beta-hANP and a radioimmunoassay for alpha-hANP that also detects beta-hANP, we have previously demonstrated that beta-hANP is converted into alpha-hANP in human plasma in vitro. In the present study, we compared the effects of intravenous administration of beta-hANP (100 micrograms) to five normal human volunteers with those of an equimolar administration of alpha-hANP (50 micrograms) to the same subjects, and we also investigated the possible mechanisms of actions of beta-hANP. Although the administration of alpha-hANP caused a significant decrease in blood pressure with a reactional increase of heart rate, beta-hANP elicited minimal change of blood pressure. In contrast, beta-hANP exerted more potent and longer lasting diuretic and natriuretic activities than did alpha-hANP. Net changes in urine volume and sodium excretion induced by beta-hANP (579 +/- 65 ml, 56.0 +/- 9.9 mEq) were significantly greater than those elicited by alpha-hANP (396 +/- 50 ml, 34.7 +/- 4.9 mEq; p less than 0.05, respectively). The administration of beta-hANP revealed a longer retention of the ANP-like immunoreactivity level in plasma, compared with that of alpha-hANP. High performance gel permeation chromatography coupled with the radioimmunoassay revealed that beta-hANP (Mr = 6000) was also converted into alpha-hANP (Mr = 3000) in human plasma in vivo. The demonstrated conversion of beta-hANP into alpha-hANP could be relevant to the observed effects of beta-hANP in humans.
Sodium sensitivity in human subjects. Hemodynamic and hormonal correlates.
Authors: Sullivan J M , Ratts T E
Published: June 2012

To investigate factors associated with sodium sensitivity, 157 subjects were studied while receiving 10 and 200 mEq sodium diets. Measurements included blood pressure (BP), forearm vascular resistance, plasma renin activity (PRA), and plasma aldosterone. Sodium repletion was associated with a greater than 5% increase in mean BP in 16% of the normotensive subjects and 29% of the borderline hypertensive subjects. Sodium-sensitive subjects were compared with sodium-resistant subjects in both the normotensive (n = 92) and borderline hypertensive (n = 65) groups. Forearm vascular resistance was significantly higher (p less than 0.05) during sodium loading in the sodium-sensitive subgroups of both the normotensive and borderline hypertensive groups (35.8 +/- 29 vs 23.8 +/- 20 [SD] and 37.5 +/- 29 vs 22.5 +/- 14 mm Hg/ml/min/100 g, respectively. Venous capacitance was lower in the sodium-sensitive than in the sodium-resistant borderline hypertensive subjects (0.8 +/- 0.21 vs 1.69 +/- 0.24 ml/100 g). During sodium restriction, PRA was significantly lower (p less than 0.01) in the sodium-sensitive subsets (2.56 +/- 1.6 vs 4.04 +/- 2.6; 2.65 +/- 2.1 vs 3.88 +/- 2.6 ng angiotensin I/ml/hr). Aldosterone was lower (p less than 0.01) during sodium depletion in the sodium-sensitive subsets (17.3 +/- 12 vs 26.3 +/- 16; 18.5 +/- 18 vs 27.9 +/- 17 ng/ml). A significant inverse correlation existed between change in BP with sodium repletion and change in PRA or level of PRA during sodium depletion (p less than 0.003).(ABSTRACT TRUNCATED AT 250 WORDS)
A comparison of nucleoside transport and metabolism in hypertensive and normotensive rats.
Authors: Bottiglieri D F , Robertson D , Jackson E K
Published: June 2012

In a previous study, we discovered that spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) are dissimilar with respect to the depressor potency differentiated between intravenously and intra-arterially infused adenosine. To test the hypothesis that this dissimilarity may reflect a difference between the two strains in adenosine transport or metabolism, we compared the kinetics of nucleoside transport (i.e., [3H]uridine uptake) in erythrocytes and the pulmonary disposition of [3H]adenosine in SHR versus WKY. [3H]Uridine uptake in rat erythrocytes was linear for 4 minutes and inhibitable with dipyridamole. Kinetic analysis (i.e., Hofstee plots) of initial uptake velocity indicated no difference between the two strains with respect to apparent Km (196 +/- 40 vs 230 +/- 29 microM in WKY and SHR, respectively) and maximum velocity (7.5 +/- 0.4 vs 8.3 +/- 0.5 pmol/2 min/12% Hct in WKY and SHR, respectively). Approximately 50% of [3H]adenosine infused into the pulmonary artery of perfused rat lung was transported into the lung, and 85% of this material was incorporated into the nucleotide pool. Radioactivity in the lung perfusate consisted initially of equal amounts of adenosine and inosine; however, within 60 seconds after administration of [3H]adenosine most of the effluent radioactivity was inosine. No differences were detected in adenosine uptake, intracellular metabolism, or extracellular metabolism in lung from SHR versus WKY. Our data indicate that any difference between SHR and WKY with respect to the biological response to adenosine cannot be attributed to differences in adenosine disposition and, therefore, must be due to pharmacodynamic differences between the strains.
Increased inositol monophosphate production in cardiovascular tissues of DOCA-salt hypertensive rats.
Authors: Eid H , De Champlain J
Published: June 2012

The purpose of the present study was to investigate alpha 1-adrenergic receptors in the heart as well as the activity and the sensitivity of the phosphoinositide pathway on tissue slices of atria, ventricles, and femoral artery of hypertensive rats treated for 4 weeks with deoxycorticosterone acetate (DOCA) and 1% saline. DOCA-salt hypertensive rats were characterized by an increased sympathoadrenal tone, as suggested by increased norepinephrine and epinephrine plasma levels. The basal activity of the phosphoinositide pathway, estimated by measuring the accumulation of inositol monophosphate in the presence of an excess of lithium, was found to be greater in atria than in ventricles and femoral artery in both normotensive and DOCA-salt hypertensive rats, but it was twofold greater in atria and ventricles of DOCA-salt hypertensive rats compared with normotensive rats. Following stimulation by norepinephrine, the production of inositol monophosphate was greater in atria and femoral artery than in ventricles in both groups. However, in DOCA-salt hypertensive rats, the production of inositol monophosphate was markedly enhanced, being about twofold greater in atria and femoral artery and about three times greater in ventricles than in tissues of normotensive rats. These differences between DOCA-salt hypertensive and normotensive animals do not appear to be associated with a difference in alpha 1-adrenergic receptor number or affinity since cardiac alpha 1-adrenergic receptor number was unchanged in hypertensive rats and the binding affinity to the receptor was significantly decreased in hypertensive rats compared with normotensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Angiotensin reactivity in the cheek pouch of the renovascular hypertensive hamster.
Authors: Myers T O , Joyner W L , Gilmore J P
Published: June 2012

Increased reactivity to vasoconstrictor agents and decreased arteriolar luminal diameter have been implicated in the maintenance of hypertension. The same hamster cheek pouch microvessels were tested for angiotensin I (Ang I) and angiotensin II (Ang II) reactivity before and 10 to 14 days after Grollman (two-kidney, one figure-8) or sham operation. Microvascular geometric parameters were measured before and after a maximal vasodilator dose of adenosine. Then maximal vasoconstrictions to Ang I or Ang II were measured: Ang I and Ang II were applied adjacent to arterioles (10(-2)-10(0) pmol) and venules (10(-1) pmol) in 10-microliter aliquots for 1 minute. Blood pressure (178 +/- 11/133 +/- 8 mm Hg) of renovascular hypertensive hamsters was elevated significantly over blood pressure of sham-operated hamsters (120 +/- 11/97 +/- 10 mm Hg). No change was observed in venular geometry or reactivity in renovascular hypertensive hamsters. Arteriolar luminal diameter, wall thickness, wall/lumen ratio, and wall area were not altered in hypertensive hamsters in the normal or vasodilated state; vasodilator capacity was the same in all groups. Conversion of Ang I to Ang II (response to Ang I divided by response to Ang II) for first-order and Third-order arterioles and third-order venules was 74 +/- 5, 79 +/- 3, and 72 +/- 6%, respectively, and was unaltered in renovascular hypertensive hamsters. Although vessel geometry was not altered, there was a significant shift to the left of the Ang I and Ang II dose-response curves of first-order and third-order arterioles, indicating increased sensitivity to these vasoconstrictors.(ABSTRACT TRUNCATED AT 250 WORDS)
Nifedipine: individual responses and concentration-effect relationships.
Authors: Donnelly R , Elliott H L , Meredith P A , Kelman A W , Reid J L
Published: June 2012

Dynamic and kinetic variability account for the large intersubject differences in the antihypertensive response to nifedipine, and a clear concentration-effect relationship has not been established. The effects of placebo, first dose, and chronic (1 and 6 weeks) treatment with nifedipine were studied in 14 subjects with essential hypertension using an integrated kinetic-dynamic model to calculate individual subject responsiveness in terms of fall in blood pressure per unit change in drug concentration. Nifedipine concentrations were well correlated with the fall in systolic blood pressure in individual subjects, and the mean responsiveness was -0.48 mm Hg/ng/ml after the first dose, -0.45 mm Hg/ng/ml after 1 week, and -0.49 mm Hg/ng/ml after 6 weeks. The responsiveness to the first dose of nifedipine was significantly correlated with the responsiveness after 1 (r = 0.83) and 6 weeks (r = 0.78) of therapy and with the height of the pretreatment blood pressure (r = 0.6). This study incorporated kinetic as well as dynamic information to characterize the antihypertensive response to nifedipine and identify nifedipine concentration-effect relationships in individual hypertensive subjects.
Erythrocyte deficiency in calpain inhibitor activity in essential hypertension.
Authors: Pontremoli S , Melloni E , Sparatore B , Salamino F , Pontremoli R , Tizianello A , Barlassina C , Cusi D , Colombo R , Bianchi G
Published: June 2012

The calpain-calpain inhibitor system was evaluated in erythrocytes of patients with essential hypertension and normotensive controls, either with or without a family history of hypertension. Calpain levels were similar in the controls and hypertensive patients, whereas the inhibitor activity level was significantly reduced in the latter (301.8 +/- 26.4 vs 220 +/- 14 U/mg hemoglobin, p less than 0.001). Borderline hypertensive patients and a few controls with a history of hypertension showed low inhibitor activity. Similar results have recently been reported in genetically hypertensive rats of the Milan strain. A significant inverse correlation (r = -0.43, p less than 0.001) was found between mean arterial pressure and calpain inhibitor. Although the pathophysiological significance of these observations is not yet clear, they suggest a new area of investigation into the molecular mechanisms underlying essential hypertension and its complications.
Atrial natriuretic factor in specific brain areas of spontaneously hypertensive rats.
Authors: Bahner U , Geiger H , Palkovits M , Heidland A
Published: June 2012

Atrial natriuretic peptides (atrial natriuretic factor, ANF) are present in a great number of brain areas inside and outside of the blood-brain barrier. The pattern of distribution implies the involvement of ANF in different physiological functions, such as blood pressure regulation, electrolyte and fluid homeostasis, and modulation of the neuroendocrine system. To further investigate a possible involvement of central ANF in spontaneous hypertension, we measured levels of ANF in 18 selected, microdissected brain areas of prehypertensive (4-week-old) and hypertensive (12-week-old) spontaneously hypertensive rats (SHR) and their normotensive control, Wistar-Kyoto rats (WKY), by radio-immunoassay. ANF was significantly decreased in seven brain areas in SHR at both ages investigated; the most pronounced decreases were found in the subfornical organ, in the perifornical and periventricular hypothalamic nuclei, and in the medial preoptic nucleus. In addition, in young SHR ANF was significantly decreased in the organum vasculosum laminae terminalis and increased in the median eminence. After the development of hypertension, a significant decrease of ANF could be detected in four more brain areas (bed nucleus of the stria terminalis, paraventricular and arcuate nuclei, dorsal raphe nucleus) of SHR, as compared with normotensive controls, and the increase in the median eminence was no longer detectable. These results suggest a role for ANF in genetic hypertension and the specific importance of certain brain regions.
Comparison of variability of urinary sodium, potassium, and calcium in free-living men.
Authors: Siani A , Iacoviello L , Giorgione N , Iacone R , Strazzullo P
Published: June 2012

The variability of 24-hour urinary sodium, potassium, and calcium excretion was studied in a sample of 22 Neapolitan men with mild blood pressure elevation. On 5 days within a 1-month period, 24-hour urine specimens were collected by each subject. The estimated ratio of intraindividual-to-interindividual variance was 1.12 for urinary sodium, 2.46 for urinary potassium, and 0.52 for urinary calcium. Based on these values, five 24-hour urine collections are necessary to reduce to less than 10% the diminution of the correlation coefficient between urinary sodium and another related variable; this number is substantially lower than that found in previous studies in a North American population sample, but similar to the one reported for Chinese population samples. Ten urinary collections are needed for potassium excretion. A different and more favorable situation is observed for 24-hour calcium excretion, as only two collections are necessary for the adequate characterization of individuals in a population.
Physiological mechanisms for calcium-induced changes in systemic arterial pressure in stable dialysis patients.
Authors: Fellner S K , Lang R M , Neumann A , Spencer K T , Bushinsky D A , Borow K M
Published: June 2012

The mechanisms by which variations in blood ionized calcium (Ca2+) influence systemic arterial pressures independent of changes in extracellular fluid volume, pH, and electrolytes are unknown. To study this issue, we dialyzed eight stable hemodialysis patients on three separate occasions during 1 week with dialysates differing only in calcium concentration. Ultrafiltration was adjusted to achieve the patient's estimated dry weight. Postdialysis Ca2+ was measured, as were arterial blood gases, electrolytes, magnesium, blood urea nitrogen, creatinine, and hematocrit. Blood pressures and two-dimensional, targeted M-mode echocardiograms were recorded with the patient in the supine position after 15 minutes of rest. Postdialysis, three different levels of Ca2+ were achieved. Other measured biochemical variables and body weight did not differ among the three study periods. Changes in Ca2+ correlated directly with changes in systolic, diastolic, and mean blood pressures, left ventricular stroke volume, and cardiac output. In contrast, heart rate, left ventricular end-diastolic dimension, and total systemic vascular resistance were not altered significantly by changes in Ca2+. Thus, alterations in Ca2+ within the physiological range affect systemic blood pressure primarily through changes in left ventricular output rather than in peripheral vascular tone in stable dialysis patients.
Flow pattern and structural changes at carotid bifurcation in hypertensive cynomolgus monkeys.
Authors: Hennerici M , Bürrig K F , Daffertshofer M
Published: June 2012

Blood flow pattern and morphological changes within the extracranial carotid system were studied in M. fascicularis before, immediately after, and at various intervals (4 hours, 4 days, 10 days, and 4 weeks) after the introduction of systemic hypertension by surgical coarctation of the thoracic aorta. Intra-arterial hemodynamics were assessed by means of both continuous-wave Doppler signal spectrum analysis and multigate pulsed-wave Doppler flow velocity profile processing. Diminished peak frequencies throughout the carotid system and enlargement of the lumen diameter in the common carotid artery and the carotid bulb were major findings and were suspected to be due to cerebral autoregulation at high levels of intracranial vascular resistance. In the internal carotid artery of pure muscular type, the lumen diameter was diminished so the carotid bulb became an area of structural and hemodynamic transition. As a consequence, flow irregularities already observed in this region before surgery considerably increased during hypertension. In addition, endothelial disarray and leucocytic adherence and activation were associated with these hemodynamic alterations within the carotid bulb. Their mutual role in early atherogenesis is discussed.
Regulation of aldosterone receptor in rat kidney cytosol by atrial natriuretic factor.
Authors: Horiuchi M , Kohashi N , Nishiyama H , Hama J , Takenaka T , Kondo H , Katori R
Published: June 2012

We investigated the effect of atrial natriuretic factor (ANF) on aldosterone receptors in the kidney cytosol, because the binding of aldosterone to aldosterone receptors in the cytosol is considered a critical step of its action. Rat atriopeptin III was injected into male Sprague-Dawley rats (200-250 g) via the femoral vein while under pentobarbital anesthesia, and aldosterone receptors in the kidney cytosol were determined. The maximum binding capacity and dissociation constant were calculated by the Scatchard analysis. Maximum binding capacity of both types of aldosterone receptor (Type I, high affinity and low binding capacity and Type II, low affinity and high binding capacity) gradually decreased after ANF injection, reached the lowest level after 2 hours, and then slightly recovered. When more than 2.5 micrograms/kg of rat atriopeptin III was injected, the density of aldosterone receptors significantly decreased. Injection of 12.5 micrograms/kg of rat atriopeptin III decreased maximum binding capacity of Type I receptor from 42.3 +/- 2.4 (mean +/- SD, n = 6) to 22.8 +/- 3.2 femtomole/mg protein (n = 6) (p less than 0.01), and that of Type II receptor decreased from 388 +/- 46 to 285 +/- 30 fmol/mg protein (p less than 0.01). Dissociation constant of both types of receptors did not change significantly after ANF injection. Plasma aldosterone concentration showed no significant change after ANF injection, and a significant change was noted after ANF administration on aldosterone receptors in the experiments on adrenalectomized rats 7 days after operation. Furosemide had no significant effect on aldosterone receptors in both normal and adrenalectomized rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Clonidine-specific antisera recognize an endogenous clonidine-displacing substance in brain.
Authors: Meeley M P , Towle A C , Ernsberger P , Char L K , McCauley P M , Reis D J
Published: June 2012

An endogenous substance in brain, clonidine-displacing substance, binds to the same receptor populations as clonidine and is biologically active. Since receptor binding sites can be modeled by using specific antiligand antibodies, we tested the hypothesis that polyclonal antibodies raised in rat and rabbit against the clonidine analog p-aminoclonidine coupled to hemocyanin would recognize compounds structurally related to clonidine, including clonidine-displacing substance. Binding to anti-p-aminoclonidine antibodies was examined by using a competitive radioimmunoassay with tritiated p-aminoclonidine as the radioligand. Central vasodepressor agents that, like clonidine, are known to bind with high affinity to both imidazole sites and alpha 2-adrenergic receptors in brain inhibited radioligand binding to anti-p-aminoclonidine antibodies. All of these agents contain imidazol(in)e and phenyl ring moieties as part of their chemical structures (e.g., oxymetazoline); a number of other compounds without one or both of these rings failed to cross-react with the antisera. Clonidine-displacing substance, partially purified from bovine brain, also inhibited specific radioligand binding to anti-p-aminoclonidine antibodies. The inhibition was dose dependent and high affinity (IC50, 4 Units). The endogenous substance had no effect on the apparent affinity of the antibodies for the radioligand, but blocked a specific number of binding sites. Immunoprecipitation experiments showed that authentic clonidine-displacing substance, that which displaces tritiated p-aminoclonidine binding to membrane receptors, is recognized by anti-p-aminoclonidine antibodies. We conclude that a unique subset of structural determinants required for ligand interaction with both imidazole and alpha 2-adrenergic receptors is critical for binding to anti-p-aminoclonidine antibodies, and that since clonidine-displacing substance is recognized by highly clonidine-specific antisera, it may also contain these determinants within its structure, namely the imidazol(in)e and phenyl ring systems.
Influence of hypertension with minimal hypertrophy on diastolic function during demand ischemia.
Authors: Lorell B H , Grice W N , Apstein C S
Published: June 2012

Hearts with advanced pressure-overload hypertrophy from systemic hypertension have been shown to have an increased susceptibility to the development of diastolic dysfunction in response to tissue hypoxia and ischemia. It is not known if this propensity to develop diastolic dysfunction in response to ischemia is dependent on the presence of a substantial increase in left ventricular mass, or alternatively, is characteristic of hearts subjected to mild chronic hypertension early in the development of cardiac hypertrophy. We tested the hypothesis that systemic hypertension associated with mild left ventricular hypertrophy increases the susceptibility to the development of diastolic dysfunction in response to demand ischemia. The effects of demand ischemia (6 minutes) were studied in hearts from New Zealand white rabbits with chronic systemic hypertension produced by the one-kidney, one-wrap method (n = 15) and compared with age-matched, sham-operated control rabbits (n = 11) with similar left ventricular mass (5.4 +/- 0.2 vs. 5.4 +/- 0.3 g, respectively). The hearts were studied using an isolated, isovolumic (balloon in left ventricle) preparation with absent pericardium that was perfused with fresh whole blood. At baseline, coronary perfusion pressure was 100 mm Hg with comparable coronary flow per gram left ventricular weight; the hearts were paced at a physiological rate of 3 Hz, and the left ventricular balloon volume was adjusted to achieve a left ventricular end-diastolic pressure of 15 mm Hg in both groups. Left ventricular balloon volume was similar in both groups and volume was thereafter held constant. At baseline, left ventricular systolic pressure (114 +/- 4 vs. 95 +/- 3 mm Hg, p less than 0.001) and developed pressure (18.9 +/- 1.2 vs. 15.1 +/- 0.9 mm Hg/g, p less than 0.05) were higher in the hearts from the hypertensive group in comparison with the control group. During the first minute of global ischemia produced by reducing coronary perfusion pressure from 100 to 20 mm Hg, there was an immediate fall in left ventricular systolic pressure in both groups without an increase in diastolic pressure. In response to the superimposition of pacing tachycardia (heart rate, 6 Hz) during the remaining 5 minutes of the period of ischemia, left ventricular developed pressure was comparable. However, isovolumic left ventricular end-diastolic pressure (measured during long diastoles obtained with transient cessation of pacing) rose to a significantly higher level in the hearts from hypertensive rabbits than in those from the control rabbits (29 +/- 3 vs. 18 +/- 2 mm Hg, p less than 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)
Prolonged converting enzyme inhibition in non-modulating hypertension.
Authors: Dluhy R G , Smith K , Taylor T , Hollenberg N K , Williams G H
Published: June 2012

Patients with normal- or high-renin non-modulating essential hypertension fail to shift their adrenal sensitivity on a low sodium diet in response to an infusion of angiotensin II (Ang II). In a prior study, 72 hours of converting enzyme inhibition (CEI) partially corrected this subnormal aldosterone response to Ang II in patients with non-modulating hypertension. Since it was uncertain whether the failure to restore normal adrenal responsiveness reflected a continued abnormality or an insufficient duration of CEI, the present study was performed wherein subjects were studied before CEI and then 72 hours and 6 weeks after CEI. Adrenal and renovascular responses were assessed in 13 subjects with normal- or high-renin hypertension in response to an infusion of Ang II (0.3, 1.0, and 3.0 ng/kg/min) in balance on a 10 meq Na+/100 meq K+ diet. Eight of 13 had a normal plasma aldosterone increment above control levels (greater than or equal to 15 ng/dl) and were classified as modulators; the remaining subjects (five of 13) were classified as non-modulators. Enalapril was then administered for 72 hours and 6 weeks, and the assessment of the Ang II dose-response relations was repeated. In the modulators, there was no change compared with levels before CEI in the aldosterone dose-response curve or threshold sensitivity to infused Ang II at either 3 days or 6 weeks after CEI administration. In the non-modulators, CEI for 72 hours partially restored aldosterone responsiveness, but more prolonged CEI for 6 weeks completely corrected the defect, restoring aldosterone responsiveness on a sodium-restricted diet to that seen in modulators and in normotensive control subjects.(ABSTRACT TRUNCATED AT 400 WORDS)
Developmental change of kidney receptor for atrial natriuretic factor in spontaneously hypertensive rat.
Authors: Ogura T , Yamamoto I , Ogawa N
Published: June 2012

Properties of human atrial natriuretic factor (ANF) binding to the crude membrane fraction of rat kidney were studied using the ANF-radiolabeled receptor assay; the developmental change of renal ANF receptors in three age groups of spontaneously hypertensive rats (SHR) was also investigated with the methods of radiolabeled receptor assay and the quantitative approach of in vitro macro-autoradiography. Temperature and incubation time greatly influenced ANF binding capacities because of the degradation of radiolabeled ligand. Addition of 5 mM MgCl2 to assay buffer was useful for the stabilization of ANF specific binding. Scatchard analysis suggested that the crude membrane fraction of rat's kidney had a single binding site with the apparent dissociation constant of 0.55 nM. In the study of the developmental change of renal ANF receptor in SHR, systolic blood pressure of the SHR at the age of 5 weeks and 12 weeks was significantly higher than that of age-matched Wistar-Kyoto (WKY) rats, but there was no significant difference in blood pressure between SHR and WKY rats at the age of 3 weeks. Concerning the radiolabeled receptor assay of ANF, the apparent dissociation constant and maximum binding capacity in SHR were low in all age groups when compared with those of WKY rats. In the in vitro macro-autoradiographic observation, the specific binding of ANF was localized mainly in the renal cortex, and these binding patterns of SHR and WKY rats were the same in all age groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Lipid alterations in renal membrane of stoke-prone spontaneously hypertensive rats.
Authors: Okamoto H , Kawaguchi H , Minami M , Saito H , Yasuda H
Published: June 2012

Phospholipase A2 activity, phospholipids, and phospholipid fatty acids were investigated in renal membrane of male stroke-prone spontaneously hypertensive rats (SHRSP) and age-matched Wistar-Kyoto rats. Renal phospholipase A2 activity increased and membranous phospholipids especially phosphatidylcholine and phosphatidylethanolamine, decreased with age in SHRSP. Arachidonate in phospholipid also decreased with age in SHRSP. To determine the effect of pressure load on the lipid alterations in renal membrane, SHRSP that received antihypertensive treatment with hydralazine, enalapril, or nicardipine for 5 weeks were compared with those without treatment. Antihypertensive treatments prevented phospholipid degradation and increased arachidonate in phospholipid relative to the control group. Phospholipase A2 activity in each group treated with antihypertensive drugs did not differ from that in the control group. These results suggest that the course of hypertension causes renal membranous phospholipid degradation and increases phospholipase A2 activity. Antihypertensive treatments may prevent these lipid alterations in SHRSP. These renal membranous structural changes may provide an explanation not only for functional abnormalities such as decreased membrane fluidity but also for the progress of hypertension.
Evidence that specific dopamine-1 receptor activation is involved in dopamine-induced renin release.
Authors: Antonipillai I , Broers M I , Lang D
Published: June 2012

Direct effects of dopamine on renin release were examined using static incubations and perifusions of rat renal cortical slices. Dopamine (10(-5)M) significantly stimulated renin release compared with control. To determine which receptors are involved in dopamine-elicited renin release, studies were performed with specific dopamine-1 and dopamine-2 receptor agonists and antagonists, as well as with alpha- and beta-adrenergic antagonists. Fenoldopam, a dopamine-1 receptor agonist, dose dependently stimulated renin secretion both in static incubations and perifusions; whereas quinpirole (10(-7)-10(-5)M), a dopamine-2 receptor agonist, was ineffective. Phentolamine (10(-4)M), an alpha-adrenergic antagonist, did not alter dopamine- or fenoldopam-induced renin release. Similarly, propranolol, a beta-blocker, did not interfere with the renin stimulation of dopamine (10(-5)M) or fenoldopam (10(-6)M) incubations or perifusion experiments; whereas propranolol significantly blocked isoproterenol action. SCH 23390 (10(-5)M), a specific dopamine-1 antagonist, blocked dopamine- and fenoldopam-induced renin. In contrast, pimozide, a dopamine-2 receptor antagonist, was ineffective. These studies indicate that dopamine is a direct renin secretogogue, and its effects seem to be mediated by specific dopamine-1 receptor activation, as neither alpha- nor beta-adrenergic blockers nor dopamine-2 receptor antagonists altered dopamine actions. The results suggest that dopamine produced locally in the kidney may stimulate renin secretion directly by dopamine-1 receptor activation.