bluuebunny/crossref_metadata_2025 huggingface dataset:
Rat atrial natriuretic peptides inhibit oxygen consumption by rat kidney.
Authors: Kohashi N , Trippodo N C , MacPhee A A , Frohlich E D , Cole F E
Published: June 2012

The inhibitory effect of high and low molecular weight native and synthetic rat atrial peptides on oxygen consumption in isolated rat kidney mitochondria and slices was measured. Oxygen consumption by mitochondria was measured in the presence of succinate and/or adenosine diphosphate, furosemide, and low and high molecular weight native and synthetic rat atrial peptides. After the addition of succinate, adenosine diphosphate limiting respiration (State 4) increased in the presence of low, but not high, molecular weight native rat atrial peptides. Furosemide caused a significant decrease in State 4 respiration (p less than 0.001). Angiotensin II and arginine vasopressin did not alter State 4 respiration. The rate of oxygen consumption after the addition of saturating adenosine diphosphate in the presence of saturating succinate (State 3 respiration) was reduced by low and high molecular weight native rat atrial peptides. Furosemide completely blocked oxygen consumption after the addition of adenosine diphosphate. Oxygen consumption was unchanged by trypsin treated (natriuretically inactive) low molecular weight rat atrial peptides and ventricular protein extracts of high and low molecular weight native rat atrial peptides. Synthetic and low molecular weight native rat atrial peptides had similar effects on mitochondrial oxygen consumption. Low molecular weight native and synthetic rat atrial peptides decreased the adenosine diphosphate to oxygen ratio, and these peptides, as well as furosemide, also induced mitochondrial swelling; none of the other rat atrial peptide combinations nor angiotensin II produced this effect. In kidney slices, basal oxygen consumption (without substrates) was stimulated by succinate.(ABSTRACT TRUNCATED AT 250 WORDS)
Reactivity to norepinephrine and effect of sodium on blood pressure during weight loss.
Authors: Fagerberg B , Andersson O K , Persson B , Hedner T
Published: June 2012

Eighteen moderately obese middle-aged men with untreated mild hypertension were randomized to two groups and placed on a low energy diet regimen for 9 to 11 weeks. In Group I (n = 10) the amount of sodium chloride in the diet maintained the urinary sodium excretion at the predieting level. Mean body mass was reduced by 9.1 +/- 0.7 (SEM) kg. Mean intra-arterial pressure showed no significant change. There were significant decreases in heart rate (p less than 0.05) and urinary norepinephrine excretion (p less than 0.05) but not in plasma concentration of norepinephrine. In Group II (n = 8) energy as well as sodium intake was restricted, with a 95 +/- 22 mmol/24 hour reduction of urinary sodium excretion. Body mass decreased by 9.3 +/- 1.1 kg, and mean arterial pressure decreased by -18.9 to -4.3 mm Hg (95% confidence interval). There were also significant reductions in heart rate (p less than 0.001) and plasma norepinephrine concentrations (p less than 0.01) but not in urinary norepinephrine excretion. The pressor response (mean arterial pressure) to norepinephrine infusion at different dose rates was significantly elevated (p less than 0.05) in Group I during dieting in comparison with baseline. The blood pressure response to norepinephrine during dieting in patients in Group II was not changed from baseline.(ABSTRACT TRUNCATED AT 250 WORDS)
Captopril potentiates chronotropic baroreflex responses to carotid stimuli in humans.
Authors: Ebert T J
Published: June 2012

Angiotensin II is a potent vasoconstrictor and has profound effects on autonomic neural mechanisms in experimental animals. Human carotid baroreflex control of arterial pressure and heart period was examined before and after acutely decreasing angiotensin II levels by administering 50 mg of oral captopril, an angiotensin converting enzyme inhibitor. Carotid baroreceptor stimuli were delivered by a neck chamber worn by 14 normotensive volunteers. Four subjects received placebo. Arterial pressure responses to carotid distention and tachycardia in response to carotid compression were not changed in captopril or placebo groups; however, there was an augmented bradycardic response to carotid stretch in captopril-treated subjects. These results indicate that captopril has an asymmetrical effect on carotid baroreflex function and suggest that enhanced baroreflex mediated bradycardia is due to a reduction in central nervous system angiotensin II levels by captopril, which augments vagal-cardiac responses to carotid stimuli.
Atrial natriuretic factor in Dahl rats. Atrial content and renal and aortic responses.
Authors: Snajdar R M , Rapp J P
Published: June 2012

Inbred Dahl salt-sensitive rats had a higher content of atrial natriuretic factor by bioassay in their atria than did inbred Dahl salt-resistant rats. This finding was true both in young 1- to 2-month-old rats, when blood pressure differences between strains were small, and in 7-month-old rats, when blood pressure differences were marked. Atria from salt-sensitive rats had more atrial natriuretic factor than did atria from salt-resistant rats when the rats were fed either low (0.3% NaCl) or high (8% NaCl) salt diet, but a high salt diet suppressed the atrial content of atrial natriuretic factor equally in both strains. In young, prehypertensive salt-sensitive rats, intravenous injections of atrial natriuretic factor caused significantly less natriuresis and diuresis than in salt-resistant rats (p less than 0.05). As the rats aged and salt-sensitive rats became markedly hypertensive, the strain responses to atrial natriuretic factor were reversed, that is, the salt-sensitive rats became more sensitive to atrial natriuretic factor than did the salt-resistant rats. Aortic vascular smooth muscle response to contraction with KCl was equally inhibited in both strains by atrial extracts or atriopeptin II. Thus, the salt-sensitive rat renal hyporesponsiveness to atrial natriuretic factor was not associated with a generalized hyporesponsiveness of vascular tissue to atrial natriuretic factor. It is argued that salt-sensitive rats could have two defects relating to atrial natriuretic factor, one involving hyporesponsive kidneys and another involving decreased release of atrial natriuretic factor from the atria.
Effects of prostaglandin synthesis inhibitors on the renin-angiotensin system and renal function.
Authors: Izumi Y , Franco-Saenz R , Mulrow P J
Published: June 2012

Equal doses (8 mg/kg) of the nonsteroidal antiinflammatory drugs indomethacin, naproxen, and sulindac and a large dose of sulindac (32 mg/kg) were administered intragastrically to conscious rats after a normal sodium diet, furosemide stimulation, and a low sodium diet for 8 days. Indomethacin, naproxen, and the high dose sulindac (32 mg/kg) decreased urinary prostaglandin E2 excretion significantly under all experimental conditions. Sulindac (8 mg/kg) suppressed prostaglandin E2 excretion after the normal and low sodium diets but not after furosemide stimulation. Indomethacin decreased plasma active renin levels under all three experimental conditions. In rats receiving a normal sodium diet, indomethacin did not affect free water clearance or renal function; however, after furosemide stimulation or a low sodium diet, indomethacin caused a significant reduction of free water clearance and glomerular filtration rate. Naproxen and sulindac (8 mg/kg) did not suppress active renin under any of the experimental conditions. However, naproxen and sulindac caused a significant reduction in free water clearance and glomerular filtration rate after furosemide stimulation and a low sodium diet. Indomethacin, naproxen, and the high dose sulindac suppressed renal prostaglandin E2 excretion under all experimental conditions. Renal prostaglandin E2 does not appear to be necessary for active renin secretion. Indomethacin is the most potent inhibitor of active renin and, therefore, most likely to cause hyporeninemia. Volume depletion appeared to sensitize the kidney to the adverse effects of nonsteroidal antiinflammatory drugs.
Mechanism of acute hypercalcemic hypertension in the conscious rat.
Authors: Berl T , Levi M , Ellis M , Chaimovitz C
Published: June 2012

Acute hypercalcemia in the conscious, unanesthetized rat, achieved by a 30-minute infusion of CaCl2 (serum calcium level, 12.8 +/- 0.6 mg/dl) resulted in significant elevation of mean arterial pressure (from 112 +/- 2 mm Hg to 129 +/- 3 mm Hg, p less than 0.001). This pressor response was associated with a significant increase in systemic vascular resistance, from 0.45 +/- 0.02 mm Hg/(ml/min)/kg body weight to 0.50 +/- 0.02 mm Hg/(ml/min)/kg body weight (p less than 0.05), but it caused no alteration in cardiac index. The pressor response to acute hypercalcemia does not appear to be mediated by vasopressor hormones or attenuated by vasodepressor hormones since inhibition of the renin-angiotensin system (nephrectomy), catecholamines (central and peripheral 6-hydroxydopamine), vasopressin (vascular antagonist), prostaglandins (indomethacin), and parathyroid hormone (parathyroidectomy) did not significantly alter the pressor response to infusion of CaCl2 in spite of similar serum calcium levels in all groups of animals. Rather, the pressor response to acute hypercalcemia seems to be mediated by a direct action of calcium ion on smooth muscle and perhaps myocardial cell contractility, since pretreatment with the calcium channel blockers verapamil or nifedipine blocked the pressor response to acute hypercalcemia.
Preferential inhibitory effect of nifedipine on angiotensin II-induced renal vasoconstriction.
Authors: Imagawa J , Kusaba-Suzuki M , Satoh S
Published: June 2012

The inhibitory effects of nifedipine on renal vasoconstrictor response to angiotensin II, norepinephrine, or renal nerve stimulation were tested in anesthetized dogs. Intrarenal infusions of nifedipine (0.3, 1, and 3 micrograms/min) dose-dependently suppressed the renal vasoconstriction induced by intrarenal injections of angiotension II (0.03, 0.05, and 0.1 microgram) or norepinephrine (0.3-1 micrograms) but not that by renal nerve stimulation (4-7 Hz). However, the inhibitory effect of nifedipine on angiotensin II-induced vasoconstriction was greater than its effect on norepinephrine-induced or renal nerve stimulation-induced vasoconstriction (i.e., 50% reduction in renal blood flow). Furthermore, a greater renal vasodilation induced by intrarenal bolus injections of nifedipine (1,3, and 10 micrograms) but not by acetylcholine (0.1 and 0.3 microgram) was observed during the reduction in the perfusion pressure of the contralateral kidney to approximately 50 mm Hg, which resulted in an increase in plasma renin activity and plasma angiotensin II concentration but no change in plasma norepinephrine concentration. There was a significant positive correlation between plasma renin activity and plasma angiotensin II concentration before nifedipine injections and the subsequent increase in renal blood flow produced by each dose of nifedipine. These results indicate that nifedipine has a relatively preferential inhibitory effect on the renal vasoconstriction produced by both exogenous and endogenous angiotensin II in canine renal vasculature.
Effects of acute renal denervation on kidney function in deoxycorticosterone acetate-hypertensive swine.
Authors: Ciccone C D , Zambraski E J
Published: June 2012

Deoxycorticosterone acetate-induced hypertension in Yucatan miniature swine appears to involve elevated peripheral sympathetic activity. Abnormalities in renal function in these hypertensive animals are also apparent. To determine the extent to which renal nerve activity controls kidney function in animals with established deoxycorticosterone acetate hypertension, the effects of acute renal surgical denervation were assessed in five normal and 10 deoxycorticosterone acetate-treated swine. After 12 to 16 weeks of treatment, mean arterial pressure rose from the normal level of 110 to 120 to 164 +/- 4 mm Hg but was decreased to 131 +/- 4 mm Hg by anesthesia. In the normal animals, blood pressure under anesthesia was 114 +/- 9 mm Hg. Acute left kidney surgical denervation significantly decreased renal vascular resistance and increased renal blood flow, glomerular filtration rate, urine flow, and sodium excretion only in the treated animals. In an additional group of six normal and eight deoxycorticosterone acetate-treated swine, the responses to renal pharmacological denervation with intrarenal guanethidine were evaluated. Guanethidine had no significant effect on renal blood flow, vascular resistance, glomerular filtration rate, urine flow, or sodium excretion in the normal animals. In contrast, in the mineralocorticoid-hypertensive animals, guanethidine significantly decreased renal vascular resistance and caused a diuresis and natriuresis with no change in glomerular filtration rate. We conclude that, in deoxycorticosterone acetate-treated miniature swine with established hypertension, renal nerve activity appears to be elevated and important in determining renal hemodynamics and sodium and water excretion.
Lithium infusion to study sodium handling in unanesthetized hypertensive rats.
Authors: Biollaz J , Waeber B , Diezi J , Burnier M , Brunner H R
Published: June 2012

To investigate renal tubular handling of sodium in various types of experimental hypertension, sodium, lithium, and inulin clearances were measured simultaneously in unanesthetized rats. Fractional excretion of lithium was used as an index of proximal sodium reabsorption. Eight groups of animals, all of the Wistar-Kyoto strain, were studied. Three were hypertensive: spontaneously hypertensive rats (SHR), rats with two-kidney, one clip renal hypertension, and uninephrectomized rats with deoxycorticosterone-salt hypertension. The five normotensive control groups included animals given normal, low, or high dietary sodium loads and rats with reduced renal mass. Fractional excretion of lithium was not influenced by moderate changes of glomerular filtration rate, but was sharply enhanced by sodium loading. Increased blood pressure was associated with enhanced urinary sodium excretion in uninephrectomized deoxycorticosterone-salt hypertensive and two-kidney, one clip hypertensive rats, as a result of decreased distal tubular reabsorption ("pressure natriuresis"). In contrast, SHR showed reduced sodium excretion and decreased fractional excretion of lithium, which suggests that increased sodium reabsorption in the proximal tubule may contribute significantly to the maintenance of hypertension.
Unusual association of hyperkalemia and hypertension.
Authors: Soppi E , Viikari J , Seppälä P , Lehtonen A , Saarinen R , Miilunpalo S
Published: June 2012

We report an unusual association of hyperkalemia, mild hyperchloremic acidosis, and hypertension in a young woman. Pseudohyperkalemia, Addison's disease, renal insufficiency, classical hyporeninemic hypoaldosteronism, isolated hypoaldosteronism, and iatrogenic causes were excluded. The patient's findings were compatible with a rare syndrome designated as type II pseudohypoaldosteronism, Gordon's syndrome.
An evaluation of self-recorded blood pressure during drug trials.
Authors: Gould B A , Hornung R S , Kieso H , Cashman P M , Raftery E B
Published: June 2012

To our knowledge, there have been no published comparisons of different techniques for measuring blood pressure during clinical trials. We undertook a comparison during clinical trials with verapamil and prazosin. During an open trial of verapamil we compared the treatment-induced blood pressure reductions as measured by clinic, intra-arterial, and self-recorded methods. The mean reduction in blood pressure was 38 +/- 13.6/20 +/- 10.1 mm Hg for clinic blood pressure, 24 +/- 17.9/16 +/- 7.3 mm Hg for self-recorded blood pressure, and 23 +/- 12.3/19 +/- 10.1 mm Hg for mean daytime intra-arterial blood pressure. During prazosin treatment the mean reduction in blood pressure was 28 +/- 21.5/18 +/- 8.5 mm Hg for clinic blood pressure, 21 +/- 20.5/6 +/- 13.7 mm Hg for self-recorded blood pressure, and 18 +/- 19.2/5 +/- 9.6 mm Hg for mean daytime intra-arterial blood pressure. There was little agreement between methods within individual patients and for group comparisons of intra-arterial or clinic methods. There was, however, good agreement between intra-arterial and self-recorded methods. This study suggests that self-recorded blood pressure recording is suitable for monitoring efficacy of antihypertensive agents in a group of patients, although caution must be exercised when interpreting the effects of therapy when measured by indirect methods in an individual patient.
Detection of primary aldosteronism by the 6-hour integrated aldosterone/renin ratio.
Authors: Zadik Z , Levin P A , Hamilton B P , Kowarski A A
Published: June 2012

An outpatient diagnostic procedure measuring the 6-hour integrated plasma concentration of aldosterone and plasma renin activity was used to detect primary aldosteronism in 12 patients with low renin hypertension, including six with mild hypertension and normal urinary excretion and spot plasma levels of aldosterone. The ratio of integrated plasma concentration of aldosterone to plasma renin activity in the 12 patients (mean, 339; range, 116-700; p less than 0.0001) did not overlap with that measured in 105 normotensive controls (mean, 27.8; range, 5-97) or in 87 subjects with essential hypertension (mean, 29.2; range, 4-67). Eight patients had surgically proven adenomas (3 of which measured less than 5 mm) with normalization of blood pressure following adrenalectomy. The four remaining patients had bilateral hyperplasia. The 6-hour integrated plasma concentration of aldosterone to plasma renin activity ratio was found to be a useful new outpatient diagnostic tool for evaluation of primary hyperaldosteronism.
Selective antagonism of the hypotensive effects of dopamine agonists in spontaneously hypertensive rats.
Authors: McCoy C E , Douglas F L , Goldberg L I
Published: June 2012

Agonists of dopamine receptors can lower blood pressure by vasodilation through action on dopamine1 receptors, inhibition of sympathetic nerve activity by action on dopamine2 receptors, or actions in the central nervous system. Fenoldopam, a selective dopamine1 agonist, piribedil, a selective dopamine2 agonist, and dipropyl dopamine, a mixed dopamine1 and dopamine2 agonist, were injected intravenously in pentobarbital-anesthetized, spontaneously hypertensive rats (SHR). The mechanism for the antihypertensive effect was evaluated by administration of the selective dopamine1 antagonist SCH 23390 and the selective dopamine2 antagonist domperidone. While SCH 23390 only antagonized the hypotensive effects of fenoldopam, domperidone abolished the fall in blood pressure produced by dipropyl dopamine and piribedil but not by fenoldopam. Increments in heart rate and plasma norepinephrine levels accompanied the hypotensive effects of fenoldopam. The increase in heart rate was abolished by a dose of SCH 23390 sufficient to completely block the hypotensive effects and was significantly attenuated by the ganglionic blocking agent hexamethonium, which suggests that the increase in heart rate was due to a baroreceptor reflex. Fenoldopam does not cross the blood-brain barrier, which suggests that its hypotensive effect was mediated by peripheral dopamine1 receptors. Since domperidone does not cross the blood-brain barrier and significantly antagonized the hypotensive and bradycardic effects of dipropyl dopamine and piribedil, these effects were mediated primarily by peripheral dopamine2 receptors. These results indicate that SCH 23390 and domperidone are useful agents to identify the receptor subtype mediating the action of dopamine agonists in SHR.
Renal alpha 2-adrenergic receptors multiply and mediate sodium retention after prazosin treatment.
Authors: Smyth D D , Umemura S , Pettinger W A
Published: June 2012

Renal nerve stimulation-induced antinatriuresis normally is mediated through post-synaptic alpha 1-adrenergic receptors; however, prazosin-induced alpha 1-adrenergic receptor blockade is associated clinically with sodium retention and not natriuresis. To study whether alpha 2-adrenergic receptors mediate renal nerve stimulation-induced antinatriuresis after chronic prazosin treatment, Sprague-Dawley rats were pretreated for 3 days with prazosin (3 mg/kg/day i.p. plus 0.15 mg/ml drinking water) or vehicle (untreated). In isolated perfused (Krebs-Henseleit; Ficoll, 3.5 g/dl, + albumin, 1.0 g/dl at 36 degrees C) kidneys from untreated rats, subpressor levels of renal nerve stimulation (approximately 1 Hz, 10 V, 1 msec) decreased (p less than 0.05) sodium (from 4.50 +/- 0.42 to 1.71 +/- .23 muEq/min) and urinary excretion rate (from 87.2 +/- 4.1 to 57.9 +/- 3.9 microliter/min). Adding prazosin (30 nM) to the perfusate completely (approximately 90%) reversed this effect (p less than 0.05), while alpha 2-adrenergic receptor blockade with yohimbine (300 nM) had no effect. In perfused kidneys from prazosin-treated rats, renal nerve stimulation decreased (p less than 0.05) sodium (from 3.24 +/- .40 to 1.32 +/- .27 muEq/min) and urinary excretion rate (from 78.7 +/- 5.0 to 54.1 +/- 5.3 microliter/min). However, adding prazosin (100 nM) to the perfusate produced only a slight, insignificant reversal of these effects; prazosin plus yohimbine were required to completely reverse the effects. These results suggest that renal nerve stimulation-induced sodium reabsorption was activated by alpha 1-adrenergic receptors in untreated rats and in part by alpha 2-adrenergic receptors in rats pretreated for 3 days with prazosin.(ABSTRACT TRUNCATED AT 250 WORDS)
Spectrum of deranged sodium homeostasis in essential hypertension.
Authors: Epstein M , Loutzenhiser R , Levinson R
Published: June 2012

Essential hypertension is thought to produce a uniform exaggerated natriuresis and diuresis. Because validation of this formulation in humans is incomplete, the natriuretic and diuretic responses to acute volume expansion were characterized by using water immersion to the neck. This method provides a volume stimulus identical to that induced by 2 L of saline without plasma compositional change. Twenty-seven subjects with essential hypertension were studied on three occasions in the seated posture while in balance on a 10 mEq Na, 100 mEq K diet: during the seated control study, during 4 hours of head-out immersion, and during saline infusion (2 L/2 hours). Four subjects had exaggerated urinary Na excretion in response to neck immersion (Group 3), and 16 had a normal response (Group 2) indistinguishable from that of 15 previously studied normal subjects. The remaining seven subjects (Group 1) had blunted or absent natriuretic responses compared with that in normal subjects (p less than 0.005). Similar results were obtained with saline administration; cumulative Na excretion in Group 1 was markedly less than that in Group 2 and the normal subjects. The heterogeneity in Na excretion indicates that an exaggerated natriuresis is not a uniform concomitant of essential hypertension. The significant inverse correlation between basal plasma aldosterone level and peak urinary as well as cumulative Na excretion suggests that plasma aldosterone constitutes a determinant of the differing natriuretic responses. In contrast to findings with urinary Na excretion, the diuretic responses of Groups 1 and 2 were identical. The striking dissociation between renal Na and water handling underscores the specificity of the derangement in renal Na handling.
Estimation of intrasynaptic norepinephrine concentrations in humans.
Authors: Goldstein D S , Zimlichman R , Stull R , Keiser H R , Kopin I J
Published: June 2012

Levels of synaptic cleft norepinephrine associated with pressor responses were estimated in humans by measuring blood pressure and arterial plasma norepinephrine during norepinephrine infusion and during yohimbine-induced release of endogenous norepinephrine. Linear pressor response-log norepinephrine concentration relationships were observed during the infusions. At a pressor response of 20 mm Hg, arterial norepinephrine averaged 3647 pg/ml. The pressor-log norepinephrine relationship was shifted more than fivefold to the left during combined ganglionic, alpha 2-adrenergic receptor, and Uptake1 (neuronal norepinephrine uptake) blockade: arterial norepinephrine averaged 684 pg/ml at a 20 mm Hg pressor response. During yohimbine-induced release of endogenous norepinephrine in desipramine-pretreated subjects, arterial norepinephrine averaged 467 pg/ml at a 20 mm Hg pressor response. Since the norepinephrine concentration in the synaptic clefts must have been between the values for plasma norepinephrine during its infusion and during its endogenous release, we estimated that in healthy people, a 20 mm Hg sympathetically mediated pressor response is associated with about a 560 pg/ml (3.3 nM) concentration of norepinephrine in the average neuroeffector junction.
Monoclonal antibodies against human renin. Blood pressure effects in the marmoset.
Authors: Wood J M , Heusser C , Gulati N , Forgiarini P , Hofbauer K G
Published: June 2012

The in vivo effects of two anti-human renin monoclonal antibodies with a high binding affinity for primate renin were studied in conscious, volume-depleted marmosets. These antibodies, R-3-17-7 and R-3-36-16, both have high binding activity for renin, but only R-3-36-16 inhibits the enzymatic activity of renin in vitro. In vivo, R-3-17-7 did not affect blood pressure after intravenous injection of doses up to 100 micrograms/kg, although plasma renin activity was partially reduced. In contrast, R-3-36-16 induced a reduction in blood pressure and an inhibition of plasma renin activity at a threshold dose of 3 micrograms/kg. The maximum fall in blood pressure and complete inhibition of plasma renin activity were observed after R-3-36-16, 10 micrograms/kg; these effects persisted for up to 2 hours. Pretreatment with a converting enzyme inhibitor or nephrectomy prevented the hypotensive effects of R-3-36-16. Conversely, pretreatment with R-3-36-16 prevented the hypotensive effects of a converting enzyme inhibitor. These findings indicate that the hypotensive response induced by R-3-36-16 is due entirely to blockade of the renin-angiotensin system. Thus, R-3-36-16 appears to be a specific, potent, and long-acting inhibitor of primate renin. Such monoclonal antibodies provide interesting tools for studying the effects of acute and chronic renin blockade.
Selection criteria for drug-treated animals in two-kidney, one clip renal hypertension.
Authors: Smith S H , Bishop S P
Published: June 2012

The two-kidney, one clip (2K1C) model of hypertension in the rat does not uniformly result in increased blood pressure. That is, the placement of a clip around one renal artery in a two-kidney rat will usually, but not always, produce hypertension. This is an important problem in studies designed to evaluate the ability of antihypertensive therapy to prevent hypertension. Therefore, an additional objective means other than blood pressure is needed to assess animals that are treated from the outset with antihypertensive therapy. The purpose of this study was to correlate the relative fresh weights of left (clipped)/right (nonclipped) kidneys (LK/RK) with tail-cuff systolic blood pressure in the 2K1C model of renal hypertension and to identify an LK/RK range that would exclude the animals least likely to become hypertensive (failures of the clipping procedure). On a scale of 0.0 to 1.0, an LK/RK ratio of 0.0 was present when the clipped kidney was completely infarcted or atrophied and a ratio of 1.0 was present when the clip did not cause sufficient renal artery stenosis to alter kidney weight. In a series of 72 untreated 2K1C male Sprague-Dawley rats examined 6 to 8 weeks after clipping, 100% of the animals with an LK/RK ratio of 0.5 to 0.8 (n = 19) and 75% with an LK/RK ratio of 0.4 to 0.9 (n = 38) had a blood pressure greater than 150 mm Hg. Less than 50% with an LK/RK ratio below 0.4 or above 0.9 (n = 34) were hypertensive.(ABSTRACT TRUNCATED AT 250 WORDS)
Hemodynamic effects of platelet activating factor in the dog kidney in vivo.
Authors: Scherf H , Nies A S , Schwertschlag U , Hughes M , Gerber J G
Published: June 2012

The effect of platelet activating factor (PAF) on renal hemodynamics and function was examined in anesthetized dogs. The infusion of PAF into the renal artery at 5, 10, and 20 ng X min-1 X kg-1 body weight resulted in dose-dependent reductions in renal blood flow, glomerular filtration rate, urine volume, and urinary sodium excretion, whereas the infusion of vehicle alone in the contralateral kidney did not result in significant changes in these parameters. The maximum decrease expressed as the percent change from baseline was 22.2 +/- 1.7% for renal blood flow, 50.8 +/- 11% for glomerular filtration rate, 67.3 +/- 4.2% for urine volume, and 69.0 +/- 8.5% for urinary sodium excretion, respectively. These renal effects were not accompanied by significant alterations in systemic arterial blood pressure and heart rate. Pretreatment with indomethacin to block prostaglandin synthesis enhanced the effect of PAF on kidney function. Our data demonstrate that, unlike the rat kidney, intrarenal PAF infusion into the intact dog results in vasoconstriction and serve reduction in glomerular filtration rate.
Effects of diltiazem on cation transport across erythrocyte membranes of hypertensive humans.
Authors: Khalil-Manesh F , Venkataraman K , Samant D R , Gadgil U G
Published: June 2012

The effects of the calcium antagonist diltiazem on diastolic blood pressure and various parameters of erythrocyte membrane cation transport were evaluated in hypertensive patients with diastolic blood pressure between 95 and 110 mm Hg in a placebo-controlled, double-blind parallel study. Twenty-one patients completed the study; 13 received placebo, while 8 received diltiazem. Diastolic blood pressure, intracellular sodium and calcium concentrations, ouabain-sensitive Na+,K+-adenosine triphosphatase (ATPase) activity, and net sodium efflux and potassium influx across red blood cell membranes were examined in both groups at the end of placebo run-in, at the end of the titration phase, and at the completion of study. In the placebo group, none of the parameters changed significantly. In the drug-treated group, diastolic blood pressure declined by approximately 10% (placebo, 95.1 +/- 8.9; drug-treated, 86.9 +/- 4.9 mm Hg; p less than 0.03) at the end of the study. There were also reductions in intracellular sodium (placebo, 7.9 +/- 1.8; drug-treated, 5.2 +/- 0.4 mmol/L cells; p less than 0.002) and calcium (placebo, 13.5 +/- 1.6; drug-treated 10.8 +/- 3.3 mumol/L cells; p less than 0.03) concentrations, accompanied by a simultaneous rise in the activity of the ouabain-sensitive Na+,K+-ATPase of erythrocyte membranes (placebo, 7.1 +/- 1.1 X 10(-2); drug-treated, 9.0 +/- 0.6 X 10(-2) microM inorganic phosphate/hr/mg; p less than 0.001) at the end of the study. However, no significant change in the ouabain-insensitive moiety of the ATPase pump was found. Diltiazem treatment increased net sodium efflux and potassium influx.(ABSTRACT TRUNCATED AT 250 WORDS)
Sodium-lithium countertransport in ambulatory hypertensive and normotensive patients.
Authors: Turner S T , Boerwinkle E , Johnson M , Richelson E , Sing C F
Published: June 2012

Numerous studies have reported the mean value for Na+-Li+ countertransport to be increased in red blood cells from patients with essential hypertension. Although concomitant variables including age, body size, national origin, geographic location, gender, and family history of hypertension may affect Na+-Li+ countertransport values, most case-control studies have failed to assess the contribution of these factors to the differences in Na+-Li+ countertransport between hypertensive and normotensive groups. The present study was undertaken to provide estimates of Na+-Li+ countertransport in hypertensive and normotensive subjects after taking into account these potentially confounding sources of variation. In 187 subjects undergoing medical evaluation at the Mayo Clinic, Rochester, MN, the combined effects of variation in age, height, and weight accounted for 20.6% of the interindividual variability in Na+-Li+ countertransport. After adjustment to remove variability due to these concomitants, differences in national origin, region of birth, and place of current residence made no additional contribution to variability in this trait. There was no significant difference in mean adjusted Na+-Li+ countertransport between men and women (0.41 +/- 0.17 vs 0.40 +/- 0.12 [SD] mmol Li efflux/L red blood cells/hr; n = 107). The mean value for adjusted Na+-Li+ countertransport was significantly greater (p less than or equal to 0.001) in subjects with essential hypertension (0.44 +/- 0.15 mmol/L red blood cell/hr; n = 104) compared with normotensive subjects (0.31 +/- 0.07 mmol/L red blood cells/hr; n = 39) or subjects with borderline blood pressure elevation (0.35 +/- 0.11 mmol/L red blood cells/hr; n = 21). Subjects with a family history of hypertension in at least one parent or full sibling had significantly higher (p less than 0.02) Na+-Li+ countertransport values (0.42 +/- 0.16 mmol/L red blood cells/hr; n = 111) than those with no family history of hypertension (0.37 +/- 0.13 mmol/L red blood cells/hr; n = 76). These results suggest that increased mean Na+-Li+ countertransport in hypertensive subjects in this sample cannot be attributed to confounding effects of variation in age, body size, gender, national origin, birthplace, or residence. Forty-eight percent of subjects with essential hypertension had adjusted Na+-Li+ countertransport values above the range observed in normotensive controls.
Peripheral dopamine receptors in the antihypertensive action of dihydroergotoxine in humans.
Authors: Mercuro G , Rossetti Z L , Rivano C A , Ruscazio M , Tocco L , Gessa G , Cherchi A
Published: June 2012

The effect of the intravenous administration of dihydroergotoxine (6 micrograms/kg) on arterial blood pressure, heart rate, and plasma concentrations of norepinephrine and 3,4-dihydroxyphenylacetic acid (the deaminated dopamine metabolite) was studied in 20 subjects with essential hypertension (8 men and 12 women aged 32-68 years old, World Health Organization Class I-II). In supine resting subjects, dihydroergotoxine significantly decreased systolic blood pressure (from 175 +/- 5 to 156 +/- 4 mm Hg; p less than 0.001), diastolic blood pressure (from 109 +/- 4 to 95 +/- 3 mm Hg; p less than 0.001), and heart rate (from 71 +/- 2 to 63 +/- 2 beats/min; p less than 0.001) as compared with the results of placebo treatment. Moreover, dihydroergotoxine reduced plasma levels of norepinephrine (from 368 +/- 39 to 238 +/- 33 pg/ml; p less than 0.001) and 3,4-dihydroxyphenylacetic acid (from 1.57 +/- 0.21 to 1.22 +/- 0.13 ng/ml; p less than 0.01). The time course of the blood pressure decrease paralleled that of plasma norepinephrine concentration. Dihydroergotoxine did not suppress the cardiovascular and plasma norepinephrine concentration. Dihydroergotoxine did not suppress the cardiovascular and plasma norepinephrine response to standing. The effect of domperidone, a peripheral presynaptic dopamine receptor antagonist, on dihydroergotoxine response was studied in six of the 20 subjects (3 men and 3 women 48-64 years old). The intravenous administration of domperidone (0.3 mg/kg) prevented the dihydroergotoxine-induced reduction in blood pressure and heart rate and the fall in plasma norepinephrine and 3,4-dihydroxyphenylacetic acid levels. Domperidone administered alone failed to significantly modify any measured variables.(ABSTRACT TRUNCATED AT 250 WORDS)
Renin dependency of the effect of chronically administered atrial natriuretic factor in two-kidney, one clip rats.
Authors: Garcia R , Gutkowska J , Cantin M , Thibault G
Published: June 2012

Conscious two-kidney, one clip rats with 150 mm Hg or higher systolic blood pressure were infused with saralasin for 60 minutes. Those with a blood pressure decline of 30 mm Hg or more were classified as saralasin-sensitive; those with a decrease of 10 mm Hg or less were considered saralasin-resistant. The animals were then housed in metabolic cages. Groups of sham-operated normotensive, saralasin-sensitive or saralasin-resistant two-kidney, one clip (2K1C) rats were infused with atrial natriuretic factor (Arg 101-Tyr 126), 100 ng/hr per rat, for 6 days. Corresponding control groups were sham-infused. Blood pressure was initially higher in the saralasin-sensitive groups (176 +/- 6 and 181 +/- 1 mm Hg, respectively) than in the saralasin-resistant groups (160 +/- 4 and 169 +/- 4 mm Hg, respectively). Atrial natriuretic factor infusion produced a gradual decline in blood pressure to 128 +/- 5 mm Hg, but only in saralasin-sensitive 2K1C animals. Urinary volume, initially higher in saralasin-sensitive hypertensive than in normotensive rats, was depressed during atrial natriuretic factor infusion. Urinary sodium excretion and water intake showed the same tendency, but the changes were not significant. No such modifications were observed in saralasin-resistant or sham-operated rats infused with atrial natriuretic factor. Body weight, which was higher in normotensive animals, was unchanged during atrial natriuretic factor infusion. Saralasin-sensitive, noninfused 2K1C rats were the only group with higher plasma renin activity than sham-operated, normotensive controls. Plasma aldosterone was higher in the former than in the other five groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Clinical significance of cognitive performance by hypertensive patients.
Authors: Elias M F , Robbins M A , Schultz N R , Streeten D H , Elias P K
Published: June 2012

Fifty-four subjects with uncomplicated essential hypertension and 54 normotensive subjects were compared with regard to a widely employed clinical index of cognitive dysfunction (the Average Impairment Rating) calculated from neuropsychological tests that discriminate between brain-damaged and neurologically normal persons. Hypertensive subjects exhibited lower mean scores on this index when education was ignored, but results were not the same for highly educated and less well educated groups. There were no differences between exceptionally well educated hypertensive and normotensive subjects, but in the less well educated group, hypertensive subjects performed more poorly than normotensive subjects. The percentages of hypertensive and normotensive subjects scoring in a cognitively impaired range on the Average Impairment Rating were low and did not differ for either education group. These data indicate the important role of subtle differences in education level with respect to positive or negative findings for studies comparing hypertensive and normotensive subjects and illustrate the important role of clinical neuropsychological indices of cognitive dysfunction when one wishes to make meaningful inferences regarding cerebral cortical function in hypertensive subjects.
A factor that initiates myocardial hypertrophy in hypertension.
Authors: Sen S , Petscher C , Ratliff N
Published: June 2012

A lack of correlation between blood pressure and myocardial hypertrophy was established in spontaneously hypertensive rats, suggesting that factors other than blood pressure control might be responsible for the modulation of myocardial hypertrophy. An in vitro system that is independent of blood pressure and hemodynamic effects was developed by use of isolated myocytes to study myocardial protein synthesis. The validity of this system was determined by means of morphology, by receptor integrity, and by studying the incorporation of tritiated leucine into myocyte protein (dpm/mg/hr). Addition of a supernatant of spontaneously hypertensive rat myocardial homogenate (centrifuged at 1500 g) to the myocyte system resulted in a significant increase in tritiated leucine incorporation into myocyte protein when compared with the addition of homogenates from normal controls. The protein from the homogenate was partially purified by high performance liquid chromatography. The resultant purified protein also stimulated protein synthesis by 70%. Furthermore, a significant increase in the specific activity of the transfer RNA and the rate of protein synthesis was observed after addition of homogenate from hypertrophied heart (4.02 +/- 0.3 vs 7.0 +/- 0.2 pmol leucine/microgram protein/hr; p less than 0.05). These data demonstrate the existence of a soluble factor in the hypertrophied myocardium that stimulated protein synthesis. This factor may play a key role in modulation of myocardial structure during development or regression of myocardial hypertrophy in hypertension.
Lymphocyte membrane sodium-proton exchange in spontaneously hypertensive rats.
Authors: Feig P U , D'Occhio M A , Boylan J W
Published: June 2012

The sodium-proton exchange activity was determined in lymphocytes of spontaneously hypertensive rats (SHR), normotensive Wistar-Kyoto rats (WKY), and domestic Wistar rats. Uptake of sodium was determined by measuring the osmotic swelling of lymphocytes after activation of the exchanger by suspension of the cells in sodium propionate and consequent intracellular acidification by the permeant weak acid. Fractional swelling (mean +/- SEM) in 16 SHR and 16 WKY was 0.44 +/- 0.03 and 0.35 +/- 0.02, respectively (p less than 0.01). The swelling was partially inhibitable by amiloride and, at 10(-4) M concentration, the amiloride-sensitive swelling was 0.21 +/- 0.02 in SHR and 0.11 +/- 0.01 in WKY (p = 0.001). Progressive extracellular ion substitutions of chloride for propionate or of potassium for sodium showed that the exchange activity was related linearly to cellular acidification; however, the dependence on extracellular sodium displayed saturation characteristics, with the same apparent Km for cells from SHR and WKY and a Vmax of 0.54 +/- 0.03 for SHR and 0.39 +/- 0.02 for WKY (p less than 0.002). External lithium could replace sodium on the exchanger but abolished the differences between strains. Results in the domestic Wistar rats were similar to those of WKY. These results suggest that lymphocytes of the SHR have a greater capacity for sodium uptake through the sodium-proton exchanger, as compared with normotensive strains. If shared by other cells, such an increased capacity could have a pathophysiological role in genetic hypertension. In particular, its presence in proximal renal tubular cells would support the hypothesis of a primary role for the kidney in the pathogenesis of genetic hypertension.
Differences in pattern of plasma angiotensinogen in native and nephrectomized rats.
Authors: Hilgenfeldt U , Schott R
Published: June 2012

Rat plasma contains two distinct forms of angiotensinogen (Ao-1 and Ao-2) that can be found in single animals in a distinct ratio. The ratio of Ao-1 to Ao-2 was determined by separation of Ao-1 and Ao-2 from 1 ml of plasma from individual rats on an SP-Sephadex C-50 column. Plasma from rats of three different strains, Wistar, Wistar-Kyoto (WKY), and spontaneously hypertensive rats (SHR), was investigated. In Wistar rats native plasma contained Ao-1 and Ao-2 in a ratio of 2.6:1. Twenty-four hours after nephrectomy, which increased the total Ao content 4.1-fold, this ratio was changed to 1.1:1. In native WKY and SHR the ratio of the two forms was similar to that in Wistar rats: 2.4:1 and 2.8:1, respectively. After nephrectomy the ratio of Ao-1 to Ao-2 was changed to 1.1:1 and 0.78:1 in WKY and SHR, respectively, while the total Ao content increased 4.9-fold and 8.2-fold in the two strains. Endogenous plasma renin inactivated the two forms of Ao, with a Km of 4.0 +/- 0.46 and 3.7 +/- 0.43 microM and a Vmax of 176 +/- 15.5 and 155 +/- 12.7 nM/hr, respectively. These results suggest that 1) Ao-1 and Ao-2 are synthesized in equimolar amounts, 2) the clearance of Ao-2 is faster than that of Ao-1 in control rats, and 3) under conditions of stimulated synthesis (i.e., after nephrectomy), the plasma content of Ao-2 increases faster than that of the more highly glycosylated form, Ao-1.
Vertex-corrected blood pressure in black girls. Relation to obesity, glucose, and cations.
Authors: Kahn H S , Bain R P
Published: June 2012

Correlates of resting blood pressure (BP) were explored among 32 inner-city, black girls, ages 11.7 to 13.9 years, a sample drawn from the second and fourth quartiles of the BP distribution in an earlier school survey. Customary BP measurements in the seated position were corrected for the height of the arterial column extending from the BP cuff to the top (vertex) of each girl's head. This vertex correction procedure has previously been shown to eliminate the childhood association between mean arterial pressure and age. Vertex-corrected systolic BP was correlated individually (p less than 0.03) with serum fasting glucose, ionized calcium, sodium, and calculated osmolality. The BP association with serum glucose did not persist after an oral sucrose challenge. Vertex-corrected diastolic BP was correlated individually (p less than 0.02) with serum ionized calcium and four indices of obesity, the best correlated of which was the subscapular skinfold (r = 0.66, p = 0.0001). Vertex-corrected BPs generally provided stronger correlations than customary (uncorrected) BPs with the variables of interest. Correlations with seated BPs were generally stronger than those with supine BPs. By multiple regression analysis, seated vertex-corrected systolic BP was related directly to serum fasting glucose and ionized calcium and inversely to pulse rate (R2 = 0.53). Seated vertex-corrected diastolic BP was related directly to subscapular skinfold and calculated osmolality (R2 = 0.54). Vertex correction may facilitate clinical or epidemiological studies of early hypertension.
Plasma norepinephrine and age as determinants of systemic hemodynamics in men with established essential hypertension.
Authors: Izzo J L , Smith R J , Larrabee P S , Kallay M C
Published: June 2012

Two primary predictor variables, age and supine plasma norepinephrine, were studied with respect to their influences on supine hemodynamic variables in 52 white men with essential hypertension who were 23 to 67 years of age and had been off active therapy for at least 4 weeks. Plasma norepinephrine was related to age (r = 0.39, p less than 0.01), correlated closely with mean arterial pressure (MAP; r = 0.54, p less than 0.0002) and systemic vascular resistance (r = 0.49, p less than 0.0005), and was related inversely to cardiac output (r = -0.26, p less than 0.06) and stroke volume (r = -0.31, p less than 0.05). Age correlated weakly with MAP (r = 0.31, p less than 0.05) and more strongly with systemic vascular resistance (r = 0.46, p less than 0.005) but was negatively related to cardiac output (r = -0.41, p less than 0.005) and heart rate (r = -0.33, p less than 0.05). Weight did not correlate with any of the hemodynamic variables. Partial regression techniques yielded significant residual correlations between age-adjusted plasma norepinephrine and MAP (r = 0.42, p less than 0.005) or systemic vascular resistance (r = 0.38, p less than 0.005). Residual correlations with cardiac output (r = -0.34, p less than 0.05), heart rate (r = -0.36, p less than 0.02), and systemic vascular resistance (r = 0.33, p less than 0.05) remained after adjusting age for the corresponding plasma norepinephrine values. These correlations demonstrate the independent effects of sympathetic nervous activity and the aging process on the systemic vasoconstriction and decreased cardiac function observed in essential hypertension.