bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations of three erythrocyte cation transport systems with plasma lipids in Utah subjects.
Authors: Hunt S C , Williams R R , Smith J B , Ash K O
Published: June 2012

To investigate the pathophysiology of essential hypertension, detailed biochemical and clinical variables were collected and analyzed for 2091 Utah subjects aged 3 to 83 years. Three different measurements of erythrocyte cation transport were obtained: Na+-Li+ countertransport, Li+-K+ cotransport, and furosemide-insensitive Li+ efflux into MgCl2. Total plasma cholesterol, triglycerides, and high density lipoprotein cholesterol levels were obtained from fasting subjects. Levels of high density lipoprotein subfractions 2 and 3 were also obtained from 350 subjects. Standardized data collection also included blood pressure, height, weight, and presence or absence of a diagnosis or treatment of essential hypertension. In univariate analyses of all 1420 adults, each of the three transport systems showed the same significant correlations with triglyceride levels (r = 0.33-0.35, p less than 0.0001), high density lipoprotein concentration (r = -0.19 to -0.21, p less than 0.001), and weight (r = 0.22-0.28, p less than 0.0001). In multivariate regression analyses, values for each transport system were significantly higher in hypertensive subjects; values for triglycerides, high density lipoprotein, and usually, the high density lipoprotein subfractions continued to have strong significant independent associations with all three transport systems; and weight remained significantly related only to Na+-Li+ countertransport. In separate logistic regressions, plasma triglyceride levels (positively, p less than 0.001) and high density lipoprotein subfraction 3 levels (inversely, p less than 0.03) were associated with hypertension itself. In multivariate analyses among 671 children, high density lipoprotein and high density lipoprotein subfraction 3 levels showed significant (p less than 0.05) inverse correlations with Na+-Li+ countertransport and furosemide-insensitive Li+ efflux.(ABSTRACT TRUNCATED AT 250 WORDS)
Antihypertensive and metabolic effects of diltiazem and nifedipine.
Authors: Schulte K L , Meyer-Sabellek W A , Haertenberger A , Thiede H M , Roecker L , Distler A , Gotzen R
Published: June 2012

The antihypertensive effect of diltiazem (180-270 mg/day) and nifedipine (40-60 mg/day) in slow-release forms was assessed over 8 weeks in a double-blind parallel study in 40 subjects with essential hypertension at rest and during exercise. Blood pressure was comparably reduced in both groups at rest as well as during exercise. The responder rates (greater than or equal to 10% reduction in diastolic blood pressure) after 8 weeks of therapy were 53% at rest and 75% during exercise in the diltiazem group and 78% and 50%, respectively, in the nifedipine group. Diltiazem decreased heart rate by 8% (p less than 0.01), while nifedipine did not affect it. As a consequence, myocardial oxygen consumption, as judged by the pressure-rate product, was reduced by diltiazem. Resting plasma norepinephrine levels were increased significantly after 8 weeks of diltiazem therapy. Plasma epinephrine, renin, aldosterone, glucose, insulin, and lactate and routine laboratory parameters were unchanged at the end of the study. No significant changes in total cholesterol and triglyceride levels were observed after 8 weeks. Whereas therapy with diltiazem resulted in an 8% fall in low density lipoprotein cholesterol after 8 weeks (p less than 0.05), nifedipine induced a drop in very low density lipoprotein cholesterol (p less than 0.05) after 8 weeks of therapy. We conclude that both diltiazem and nifedipine are effective antihypertensive agents lacking undesirable metabolic side effect. Diltiazem, however, had the advantage of lowering heart rate and myocardial oxygen consumption.
Role of sodium in modulation of myocardial hypertrophy in renal hypertensive rats.
Authors: Sen S , Young D R
Published: June 2012

To evaluate the role of dietary sodium and antihypertensive drugs in the modulation of myocardial structure, especially myosin isozymic pattern, renal hypertensive rats (two-kidney, one clip) were treated with a sodium-deficient diet (7 mEq/kg), captopril, or atenolol. Native myosin was extracted under nondissociating conditions and separated by polyacrylamide gel electrophoresis. The percentage of myosin isozyme V1 was significantly decreased from 71.5 +/- 7.5 (Wistar controls) to 52.4 +/- 1.7% (p less than 0.05) in renal hypertensive rats and was associated with an increase in V3 component from 12.7 +/- 5.1 (Wistar controls) to 23.1 +/- 1.4% (renal hypertensive rats; p less than 0.05). There was a dramatic change in the myosin isozyme distribution pattern after treatment with low sodium and captopril. Six weeks of low sodium therapy in renal hypertensive rats resulted in an increase in V1 from 52.4 +/- 1.7 to 74.8 +/- 4.8% and a reduction in V3 from 23.1 +/- 1.4 to 9.5 +/- 2.4%. Normal rats treated with low sodium showed similar results. The percentage distribution of isozymes after low sodium therapy in the captopril-treated rats was not different from that in normal Wistar controls. Captopril therapy also caused an increase in V1 and a decrease in V3. Atenolol therapy, on the other hand, caused a significant increase in V3 and decrease in V1 with no change in blood pressure or heart weight. These data suggest that dietary sodium may play an important role in the modulation of myocardial mass and may modulate signals for synthesis of V1 or V3 myosin phenotypes.
Metabolism and storage of catecholamines in rats with pheochromocytoma implants.
Authors: Buu N T , Kuchel O , Manger W , Hulse M C , Chute R N
Published: June 2012

New England Deaconess Hospital rats implanted with a pheochromocytoma P259 became hypertensive and showed high concentrations of plasma dopamine (42.0 +/- 14.6 ng/ml) and norepinephrine (45.7 +/- 8.4 ng/ml). However, the norepinephrine content of several peripheral tissues of these rats did not differ from those of the New England Deaconess Hospital control rats, and their dopamine content, although slightly higher, was much lower than would have been expected from the plasma dopamine levels. Methylation by catechol-O-methyltransferase did not appear to play a major role in the inactivation of tissue catecholamines since there were no noticeable increases of normetanephrine or 3-methoxytyramine in the tissues of the rats with pheochromocytoma. There was also no increase in conjugated dopamine, in either the sulfate or glucuronide form, in the plasma or tissue of the hypertensive rats, although injection of L-dopa induced a large increase in dopamine sulfate in the plasma and urine of these rats. This finding indicated that, although their sulfoconjugation mechanism was intact and not affected by the pheochromocytoma, it did not participate in the metabolism of dopamine released by the tumor into the blood. On the other hand, plasma and urine of tumor-bearing rats exhibited abnormally high concentrations of homovanillic acid, the main metabolite of dopamine resulting from monoamine oxidase action. In contrast to the control rats, intravenous infusion of free dopamine in rats with pheochromocytoma had no effect on plasma free dopamine levels but increased homovanillic acid levels considerably. The present data underline the important role of monoamine oxidase in the removal of excessive quantities of catecholamines released by the tumor in New England Deaconess Hospital rats with the pheochromocytoma implant.
A case of adrenal tumor producing renin, aldosterone, and sex steroid hormones.
Authors: Iimura O , Shimamoto K , Hotta D , Nakata T , Mito T , Kumamoto Y , Dempo K , Ogihara T , Naruse K
Published: June 2012

A 27-year-old woman with an adrenal tumor that produced renin and aldosterone, associated with hypertension and adrenogenital syndrome, is described. Severe hypertension, cardiomegaly, a low serum potassium level, clinical symptoms of adrenogenital syndrome, and a left upper abdominal tumor also were found. Endocrinological studies showed that plasma and urinary levels of sex steroid hormones such as dehydroepiandrosterone, androsterone, and testosterone were markedly increased. Plasma renin activity, plasma angiotensin II, and plasma aldosterone levels also were increased markedly, although deoxycorticosterone levels remained within the normal range. The possibility of renovascular hypertension was excluded by angiography of the renal artery and by venous sampling of plasma renin activity. Abnormal elevations in plasma aldosterone levels persisted despite normalization of plasma angiotensin II by converting enzyme inhibitor administration. It was suspected that this patient had an adrenal tumor producing renin as well as sex steroids and aldosterone. Microscopy of the resected tumor revealed that the tumor was composed mostly of cells with large nuclei and light cytoplasm. The tumor contained dehydroepiandrosterone, dehydroepiandrosterone sulfate, testosterone, aldosterone, and renin. Immunohistochemical study showed that some of the tumor cells produced renin. Biopsy of the left renal tissue showed evident atrophy of the juxtaglomerular cells and pronounced arteriosclerosis. After resection of the tumor, all blood and urinary levels of the abnormally increased hormones returned to a normal range and an apparent fall of blood pressure was noted. To our knowledge, this is the first report of a renin and aldosterone-producing adrenal tumor associated with hypertension and adrenogenital syndrome.
Postsynaptic alpha 1- and alpha 2-adrenergic receptors in adrenergic control of capacitance vessel tone in vivo.
Authors: Elsner D , Stewart D J , Sommer O , Holtz J , Bassenge E
Published: June 2012

The involvement of postsynaptic alpha 2-adrenergic receptors in the adrenergic constriction of the capacitance vessels was studied in anesthetized, spontaneously breathing dogs under ganglionic blockade (hexamethonium, 10 mg/kg + 10 mg/kg/hr; methylatropine, 0.5 mg/kg). Effective vascular compliance was measured as an indicator of venous tone (blood volume was varied by +/- 4 ml/kg in an 11-minute cycle of infusion, withdrawal, withdrawal, and reinfusion) and was calculated from the correlation between the observed changes in central venous pressure and the changes in blood volume. Sympathetic activity and central venous pressure were lower and effective vascular compliance was higher than values in untreated conscious dogs. The alpha 2-agonist UK 14,304 (5-bromo-6-[imidazolin-2-ylamino]-quinoxaline; 0.04 and 0.12 micrograms/kg/min; n = 6) dose-dependently lowered compliance and increased central venous pressure to levels found in conscious dogs, as did the alpha 1-agonist methoxamine (10 and 30 micrograms/kg; n = 6). Rauwolscine (alpha 2-antagonist), 0.3 mg/kg, significantly attenuated the effects of UK 14,304, but not those of methoxamine, while prazosin (alpha 1-antagonist), 0.12 mg/kg, attenuated the effects of methoxamine, but not those of UK 14,304 (n = 6 each). Under beta-blockade (nadolol, 2 mg/kg; n = 12) venous tone was increased to about physiological levels by norepinephrine, 0.15 micrograms/kg/min i.v., or by neuronal norepinephrine release induced by tyramine, 10 micrograms/kg/min i.v. These increases were significantly attenuated by prazosin as well as by rauwolscine and were abolished by a combination of both. These results indicate that postsynaptic alpha 2-adrenergic receptors (in addition to alpha 1-adrenergic receptors) are functional in the venous system in vivo and contribute substantially to adrenergic sympathetic and humoral regulation of venous tone.
Brain corticotropin releasing factor in the spontaneously hypertensive rat.
Authors: Hattori T , Hashimoto K , Ota Z
Published: June 2012

Corticotropin releasing factor and vasopressin were measured in major brain regions including the neurohypophysis in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) during development of hypertension. The highest concentration of corticotropin releasing factor was found in the hypothalamus in both strains. Corticotropin releasing factor was decreased in most major brain regions of SHR. In the hypothalamus, corticotropin releasing factor was lower in 3- and 6-week-old SHR than in age-matched WKY (p less than 0.01), but was similar at 12 and 24 weeks of age. The content of corticotropin releasing factor did not differ in the neurohypophysis in 3-week-old rats but began to decrease at 6 weeks of age (p less than 0.01) and continued to decrease during the development of hypertension (p less than 0.01). Brain vasopressin concentration did not differ between SHR and WKY except in the hypothalamus. The level of hypothalamic vasopressin was consistently lower in SHR than in WKY (p less than 0.01). These peptides are thought to be associated with autonomic nervous regulation, and our results may further strengthen the possibility that the deficit of the peptides may be involved in the development of spontaneous hypertension.
Systemic and renal vascular responses to dietary calcium and vitamin D.
Authors: Zawada E T , TerWee J A , McClung D E
Published: June 2012

To assess the consequences of hypercalcemia on systemic and renal hemodynamics, vasoactive hormones, and water and electrolyte excretion in intact, conscious mongrel dogs, measurements in 10 dogs receiving 100 mg/kg calcium gluconate and 10,000 U/kg vitamin D daily for 2 weeks were compared with measurements made in 10 time-control dogs not receiving calcium or vitamin D. Hypercalcemia induced by dietary supplementation with calcium and vitamin D resulted in profoundly reduced glomerular filtration rate (40 vs 78 ml/min in controls; p less than 0.005), estimated renal plasma flow (145 vs 267 ml/min in controls; p less than 0.005), and renal blood flow (254 vs 441 ml/min in controls; p less than 0.005). Renal resistance was significantly increased in the hypercalcemic dogs (0.57 +/- 0.07 vs 0.28 +/- 0.01 mm Hg/ml/min; p less than 0.005). Hypercalcemia also resulted in increased fractional excretion of water (4.8 vs 1.4% in controls; p less than 0.005), sodium (1.4 vs 0.6% in controls; p less than 0.005), calcium (1.7 vs 0.7% in controls; p less than 0.01), and magnesium (10.2 vs 4.1% in controls; p less than 0.005). Systolic blood pressure (160 vs 172 mm Hg in controls; p less than 0.05) and stroke volume were lower (0.024 vs 0.036 L/beat in controls; p less than 0.005) in hypercalcemic dogs, presumably because of the diuresis, while total peripheral resistance was higher (36 vs 31 mm Hg/L/min; p less than 0.05) in controls. Magnesium levels were significantly lower in the experimental group (1.3 vs 1.7 mg/dl in controls; p less than 0.0005). Aldosterone levels, plasma renin activity, and urinary prostaglandin excretion were not significantly affected.(ABSTRACT TRUNCATED AT 250 WORDS)
Diuretic treatment alters clonidine suppression of plasma norepinephrine.
Authors: Hui T P , Krakoff L R , Felton K , Yeager K
Published: June 2012

The effect of short-term diuretic treatment on the action of clonidine was evaluated in eight subjects with mild, uncomplicated hypertension. A single oral dose of clonidine (0.3 mg) was given before and after 1 week of therapy with hydrochlorothiazide, 50 mg, and amiloride, 5 mg, taken daily. Changes in mean arterial pressure, heart rate, plasma norepinephrine and epinephrine levels, and plasma renin activity were assessed. Diuretic treatment caused a significant weight loss, increased plasma renin activity, and reduced serum potassium concentration but did not significantly alter the absolute reduction in mean arterial pressure caused by clonidine. Absolute clonidine-induced reduction in plasma renin activity after diuretic treatment was three times greater than before treatment, although percent changes were similar. Before diuretic therapy, clonidine significantly reduced the level of norepinephrine (absolute and percent change). After diuretic treatment, clonidine failed to suppress norepinephrine, and the difference from prediuretic changes was significant. The level of epinephrine was not altered significantly either by diuretic treatment or clonidine. These results indicate that diuretic therapy alters the clonidine-activated mechanism for reduction of arterial pressure through a shift from overall suppression of sympathetic tone to pathways that are more restricted to renal tone. This shift may be due to changes in fluid or electrolyte balance that alter the action of alpha 2-adrenergic receptor-mediated pathways. Use of the clonidine suppression test for the diagnosis of pheochromocytoma may give false-positive results in diuretic-treated patients.
Blood pressure, body fat, and dehydroepiandrosterone sulfate variation in adolescence.
Authors: Katz S H , Hediger M L , Zemel B S , Parks J S
Published: June 2012

Several significant interrelations among variation in blood pressure, body fat, and adrenal androgen levels, as assessed by serum dehydroepiandrosterone sulfate concentrations, were found in black male and female adolescents, aged 12 to 16 years. In girls, high levels of dehydroepiandrosterone sulfate were associated with significantly higher levels of blood pressure (alpha = 0.05), even after adjusting for the significant association between increased levels of dehydroepiandrosterone sulfate and body fat. The increased body fat (i.e., body mass index) found with higher levels of dehydroepiandrosterone sulfate in girls was related to significantly greater (alpha = 0.05) accumulations of fat in the upper trunk, as opposed to the limb. In boys, high levels of serum dehydroepiandrosterone sulfate, low body mass index, and significantly higher blood pressure were interrelated (alpha = 0.05). In addition to the interaction of increased body mass index or body fat and increased levels of dehydroepiandrosterone sulfate in association with higher blood pressure, high levels of the adrenal androgen, even in boys with low body mass index, were associated independently with relatively higher blood pressure. Body proportion analyses for these boys indicated that they were tall and thin, in contrast to the other boys with low body mass index, who were generally short and thin.
Alpha 1-adrenergic blockade and cardiovascular pressor responses in essential hypertension.
Authors: Beretta-Piccoli C , Ferrier C , Weidmann P
Published: June 2012

The effects of selective alpha 1-adrenergic blockade with terazosin on blood pressure and cardiovascular pressor responsiveness were assessed in 17 subjects with mild to moderate essential hypertension (mean age, 48 +/- 2 [SEM] years). As compared with a 2-week placebo period, 8 weeks of terazosin treatment (mean dose, 10.5 +/- 1.7 mg/day) caused a fall of supine (from 153/103 +/- 3/2 to 143/96 +/- 4/2 mm Hg; p less than 0.025) and upright (from 145/106 +/- 4/2 to 131/94 +/- 5/3 mm Hg; p less than 0.01) arterial pressure; a marked blunting of cardiovascular pressor responsiveness to norepinephrine, as judged from the pressor dose (from 73 +/- 9 to 2156 +/- 496 ng/kg/min; p less than 0.02) and from the rightward shift (p less than 0.01) of the plasma concentration-blood pressure response curve; and a slight increase in plasma norepinephrine concentration (from 37.7 +/- 3.3 to 52.2 +/- 7.8 ng/dl; p less than 0.01). Heart rate, body weight, exchangeable sodium, blood volume, and norepinephrine plasma clearance; plasma epinephrine, renin, angiotensin II, and aldosterone levels; the relationships between angiotensin II-induced increases in arterial pressure or plasma aldosterone and the concomitant increments of plasma angiotensin II; and heart rate responsiveness to isoproterenol did not change significantly after terazosin treatment. These findings suggest that the fall of arterial pressure induced by selective alpha 1-adrenergic blockade in subjects with essential hypertension is associated with, and probably explained by, inhibition of alpha 1-mediated, noradrenergic-dependent vasoconstriction. alpha 1-Adrenergic receptor antagonism did not modify body sodium concentration, the adrenomedullary component of the sympathetic nervous system, angiotensin II levels, or beta-adrenergic dependent mechanisms.
Prehypertensive changes in sodium transport induced by deoxycorticosterone acetate in incubated rat tail artery.
Authors: Friedman S M , McIndoe R A , Tanaka M
Published: June 2012

The transport and distribution of sodium, potassium, and water were examined in tail arteries of rats treated with deoxycorticosterone acetate (DOCA)-saline for 10 days, a time that marks the earliest onset of a rise of blood pressure in the strain (Wistar) used. The arteries were incubated for more than 20 hours to ensure that any change observed was sufficiently built in so that it could not readily be washed out. Three distinct changes were observed. First, the steady state transmembrane sodium gradient (operationally [Na]o/[Na]i) was increased. Second, the amount of sodium excluded from participation in the sodium gradient, and hence probably bound, was increased. Third, after prolonged potassium depletion, the ouabain-insensitive loss of cell water and sodium that follows the readmittance of potassium was increased. These results suggest that fundamental embedded changes in sodium transport occur well before the blood pressure rises in response to DOCA-saline.
Failure of plasma norepinephrine to consistently reflect sympathetic activity in humans.
Authors: Floras J , Vann Jones J , Hassan M O , Osikowska B A , Sever P S , Sleight P
Published: June 2012

To determine whether venous plasma norepinephrine concentrations consistently reflect changes in sympathetic nervous activity, the influence of mental arithmetic, static handgrip, and submaximal bicycle exercise on intra-arterial blood pressure, heart rate, and plasma norepinephrine was studied in 51 subjects with untreated essential hypertension (mean age, 46 years; range, 16-69 years). At rest, plasma norepinephrine was unrelated to age or blood pressure. Mental arithmetic increased mean arterial pressure from 108 +/- 18 to 127 +/- 18 mm Hg (mean +/- S.D.; p less than 0.001) and heart rate from 69 +/- 7 to 93 +/- 13 beats/min (p less than 0.001) but not plasma norepinephrine (547 +/- 297 to 518 +/- 250 pg/ml). Isometric exercise raised mean arterial pressure from 115 +/- 18 to 148 +/- 21 mm Hg (p less than 0.001) and heart rate from 76 +/- 9 to 95 +/- 13 beats/min (p less than 0.001) but not plasma norepinephrine (683 +/- 253 to 741 +/- 253 pg/ml). Bicycle exercise increased mean arterial pressure from 114 +/- 20 to 146 +/- 26 mm Hg (p less than 0.001), heart rate from 77 +/- 9 to 128 +/- 19 beats/min (p less than 0.001), and plasma norepinephrine from 645 +/- 228 to 1151 +/- 462 pg/ml (p less than 0.001). Both the maximum mean arterial pressure and the peak heart rate attained during bicycle exercise were related to the exercise plasma norepinephrine level (r = 0.33, p less than 0.02 and r = 0.28, p less than 0.03, respectively). Increases in plasma norepinephrine with exercise were not greater in older or more hypertensive subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
Noncardiogenic pulmonary edema as the sole manifestation of pheochromocytoma.
Authors: de Leeuw P W , Waltman F L , Birkenhäger W H
Published: June 2012

A 40-year-old man was admitted to the hospital with pulmonary edema without signs of left ventricular failure. Noncardiogenic pulmonary edema was diagnosed, and a subsequent workup identified a pheochromocytoma as the cause of this condition. The clinical picture could be mimicked by infusion of exogenous norepinephrine. It is concluded that surges of catecholamines from a pheochromocytoma may provoke pulmonary edema in a manner similar to that by which neurogenic pulmonary edema related to cerebral disorders occurs.
Effect of cold pressor test-induced stress on leukocyte sodium transport and norepinephrine.
Authors: Riozzi A , Heagerty A M , Bing R F , Thurston H , Swales J D
Published: June 2012

The effects of stress on leukocyte membrane sodium efflux rate constant and plasma norepinephrine levels were studied before and during cold pressor test in normotensive subjects with and without a family history of hypertension. After 20 minutes of supine rest, no significant differences in total, ouabain-resistant or ouabain-sensitive sodium efflux rate constants were apparent between the two groups. In normotensive subjects with no family history, there was no significant change in any efflux rate constant during cold pressor test, although there was a highly significant negative correlation between change in total efflux rate constant and change in norepinephrine levels (r = -0.82, p less than 0.01, n = 12). During cold pressor test in subjects with a family history of hypertension, there was a significant rise in the ouabain-resistant efflux rate constant (1.5 +/- 0.1 vs 1.0 +/- 0.1 hr-1; p less than 0.01, n = 10); this level was also significantly higher than that in control subjects (p less than 0.002). In this group, the ouabain-sensitive efflux rate constant fell slightly but not significantly (1.8 +/- 0.2 vs 2.1 +/- 0.2 hr-1; n = 10). These results suggest that stress in the form of a cold stimulus produces qualitative differences in leukocyte cation transport in normotensive offspring of hypertensive patients as compared with subjects without such a family history.
A high phosphate diet lowers blood pressure in spontaneously hypertensive rats.
Authors: Bindels R J , van den Broek L A , Hillebrand S J , Wokke J M
Published: June 2012

Plasma phosphate values are significantly lower in spontaneously hypertensive rats (SHR) than in normotensive Wistar-Kyoto rats (WKY). In this study, we increased plasma phosphate in SHR by a dietary phosphate intake and followed the effects on blood pressure. Fifteen male WKY and 15 male SHR were housed from 4 weeks of age up to 26 weeks. At 4 weeks of age all SHR manifested a hypophosphatemia compared with age-matched WKY (F = 62, p less than 0.0003). At 5 weeks of age, the rats were divided into three diet groups: a control group, a group receiving 1.41% (wt/vol) KCl in drinking water, and a group receiving 2% (wt/vol) K2HPO4 X KH2PO4 in drinking water. In the control (F = 16.2, p less than 0.02) and KCl groups, (F = 36.3, p less than 0.03), hypophosphatemia persisted throughout the study. The phosphate-supplemented diet normalized plasma phosphate level in SHR but did not change plasma phosphate level in WKY. As a consequence, no difference in plasma phosphate level between WKY and SHR was present in the group receiving additional phosphate from that time on (F = 1.2, p greater than 0.41). The phosphate-supplemented diet significantly decreased systolic blood pressure in both strains. In phosphate-supplemented SHR, a significant decline in systolic blood pressure was observed from 20 weeks of age on (at 20 weeks of age: 222 +/- 3 mm Hg for control SHR vs 198 +/- 5 mm Hg for phosphate-supplemented SHR; p less than 0.0003).(ABSTRACT TRUNCATED AT 250 WORDS)
Atrial natriuretic factor during development and reversal of one-kidney, one clip hypertension.
Authors: Garcia R , Cantin M , Gutkowska J , Thibault G
Published: June 2012

Atrial natriuretic factor (ANF) was studied in rat plasma and atria 1, 2, 4, 6, and 8 weeks after constriction of the left renal artery and removal of the contralateral kidney. Plasma ANF was elevated at all periods of investigation. A positive correlation was observed between plasma ANF and blood pressure (r = 0.56, p less than 0.001). The total atrial ANF content (microgram/atrium) in one-kidney, one clip (1K1C) rats was lower during Weeks 1 and 2, but only in the left atrium. Lower ANF concentrations (microgram/mg protein) were also evident in the left atrium at Weeks 1, 2, and 8, and in the right atrium at Week 8. A negative correlation between ANF in plasma and in the left atrium was discerned (r = 0.43, p less than 0.01). Blood pressure (184 +/- 4 vs 114 +/- 4 mm Hg), body weight, and plasma ANF were also examined in 1K1C rats and their normotensive controls before and after unclipping. Blood pressure was normalized 6 hours after unclipping. Plasma ANF declined in 1K1C rats within 6 hours after clip removal, but it was still higher than in the controls. Plasma ANF was similar in both groups on Days 9 and 13 after unclipping. There were no differences in atrial ANF between hypertensive and normotensive animals 13 days after unclipping. The high levels of plasma ANF observed in 1K1C rats probably are secondary to increased intra-atrial pressure caused by the dual mechanism of expanded plasma volume and high blood pressure.
Comparison of a new renin inhibitor and enalaprilat in renal hypertensive dogs.
Authors: Smith S G , Seymour A A , Mazack E K , Boger J , Blaine E H
Published: June 2012

The hypotensive efficacy of a potent new renin inhibitor (N alpha-isovaleryl-L-histidyl-L-prolyl-L-phenylalanyl-L-histidyl-ACHPA+ ++-L- phenylalanyl amide) containing (3S,4S)-4-amino-5-cyclohexyl-3-hydroxy pentanoic acid (ACHPA) was compared with the converting enzyme inhibitor (enalaprilat) (MK-422) in conscious one-kidney dogs before and after tightening a renal artery clamp. Dose-response curves to 0.003 to 0.1 mg/kg/min i.v. infusions of the ACHPA-containing renin inhibitory peptide or enalaprilat (0.003-0.1 mg/kg i.v. bolus) were obtained in one-kidney dogs before and 3 days and 14 days after renal artery constriction. The ACHPA-containing renin inhibitory peptide and enalaprilat maximally decreased blood pressure by 10 +/- 2 and 9 +/- 2 mm Hg before constriction and by 12 +/- 2 and 12 +/- 4 mm Hg in dogs treated 14 days after renal artery constriction, respectively. Glomerular filtration rate and effective renal plasma flow were unaltered or slightly improved. In sharp contrast, both compounds elicited significant, dose-related decreases in blood pressure (-26 +/- 4 and -20 +/- 4 mm Hg, respectively), glomerular filtration rate (-21 +/- 3 and -23 +/- 3 ml/min), and renal plasma flow (-45 +/- 14 and -48 +/- 13 ml/min) in dogs examined 3 days after renal artery constriction. These data demonstrate that ACHPA-containing renin inhibitory peptide and enalaprilat are equally effective antihypertensive agents in dogs with renin-dependent renovascular hypertension and lend credence to the contention that the renin-angiotensin system supports renal function in hypertensive states in which renin levels are elevated.
Microvascular tone in a skeletal muscle of spontaneously hypertensive rats.
Authors: Schmid-Schönbein G W , Zweifach B W , DeLano F A , Chen P C
Published: June 2012

We studied the degree of arteriolar smooth muscle constriction in the spinotrapezius muscle microcirculation of spontaneously hypertensive rats and their normotensive controls, Wistar-Kyoto rats. The constriction was expressed in the form of a nondimensional tone as the difference between steady state and dilated diameter (after papaverine treatment) divided by the dilated diameter. Both animal strains showed on average a progressive increase of tone toward the more distal arterioles, with a peak tone being reached in the transverse arterioles. Tone values in the hypertensive animals were consistently elevated. The number of arterioles that had more than 5% tone (so-called responder arterioles) was higher in the hypertensive animals. These studies suggest that, besides the anatomical adjustments documented earlier in our laboratory in the arteriolar network of this muscle, functional adjustments in the form of an elevated microvascular tone are associated with the elevated resistance in spontaneously hypertensive rats.
Vascular responsiveness to serotonin metabolites in mineralocorticoid hypertension.
Authors: Thompson L P , Webb R C
Published: June 2012

This study characterizes vascular responsiveness to serotonin and its metabolites and to several monoamines that are structurally related to serotonin in deoxycorticosterone acetate (DOCA)-salt hypertension. Mesenteric arteries from normotensive and hypertensive rats were excised and cut into helical strips for isometric force recording. Dose-response curves to serotonin in arteries from hypertensive rats were shifted significantly to the left compared with those in arteries from normotensive rats (ED25: DOCA-treated = 2.4 X 10(-8) M; control = 17.1 X 10(-8) M). Contractile responses to 5-hydroxyindole acetic acid and 5-hydroxytryptophol were greater in mesenteric arteries from hypertensive rats, whereas reactivity to 5-methoxytryptamine and melatonin in arteries from hypertensive rats did not differ from that in arteries from normotensive rats. Mesenteric arteries from both rat groups were unresponsive to the serotonin metabolite N-acetylserotonin. Contractile responses to 5,6-dihydroxytryptamine and 6-hydroxytryptamine were greater in mesenteric arteries from hypertensive rats, whereas responsiveness to 3-hydroxytryptamine in hypertensive arteries did not differ from normotensive values. Contractile responses to serotonin and its metabolites and to the structurally related monoamines were inhibited by the serotonergic antagonist ketanserin. These results demonstrate that vascular sensitivity to serotonin is increased in DOCA-hypertensive rats. Based on the experiments with serotonin metabolites and with other monoamines, the increased responsiveness to these compounds appears to be related to the structural location of hydroxyl and amine moieties.
The search for a hypothalamic Na+,K+-ATPase inhibitor.
Authors: Haber E , Haupert G T
Published: June 2012

Accumulating experimental evidence suggests that natriuresis in response to intravascular volume expansion is promoted by an endogenous regulator of Na+,K+-adenosine triphosphatase (ATPase). Efforts to purify this substance by a number of laboratories have as yet been unsuccessful. The properties of partially purified inhibitors from plasma, urine, and tissue often fail to possess the characteristics thought to be consistent with those of a physiological regulator. These include potency (Ki of approximately 1 nM), reversibility of inhibition, specificity for Na+,K+-ATPase, and responsiveness to relevant physiological stimuli. Two rather different candidate substances, extracted from urine and hypothalamus, have been purified to a high degree. Neither is a peptide, and both are of low molecular weight and resistant to acid hydrolysis. The substance from urine is rather nonpolar and interacts with digoxin-specific antibodies, while that from hypothalamus is polar and does not appear to share epitopes with the cardiac glycosides. On the serosal surface of the toad urinary bladder, the hypothalamic substance causes a reversible inhibition of Na+ transport, inhibits rubidium uptake in red blood cells by acting on the membrane's exterior surface, inhibits binding of ouabain to purified Na+,K+-ATPase, and reversibly inhibits hydrolysis of adenosine 5'-triphosphate by the enzyme with a Ki of 1.4 nM. The hypothalamic inhibitor may be differentiated from ouabain by their respective ionic requirements for optimal inhibition of enzymatic activity, and although both ouabain and the hypothalamic inhibitor fix Na+,K+-ATPase in its E2 conformation, the hypothalamic inhibitor does not promote phosphorylation of the enzyme by inorganic phosphate in the presence of Mg2+. Ionic requirements for inhibition also differentiate the hypothalamic inhibitor from vanadate ion, as does the inhibitor's activity in the presence of norepinephrine. Further enzymological and physiological studies will be facilitated by structural characterizations of the inhibitory substances and by the availability of a method to measure their concentrations in physiological fluids.
Effects of atrial natriuretic factor on hormone-induced renin release.
Authors: Deray G , Branch R A , Herzer W A , Ohnishi A , Jackson E K
Published: June 2012

The purpose of this study was to determine whether or not atrial natriuretic factor can act directly on the juxtaglomerular cell in vivo to inhibit hormone-induced renin release. To achieve this objective the interaction between synthetic atrial natriuretic factor and two different renin secretagogues was examined. To exclude any indirect effect of atrial natriuretic factor on renin release due to changes in sodium delivery to the macula densa, all studies were conducted in nonfiltering, canine kidneys. In one series of studies renin release was stimulated by intrarenal infusions of norepinephrine (3 micrograms/kg/min), and in a second series of studies renin release was induced by intrarenal infusions of prostacyclin (0.1 micrograms/kg/min). In both studies intrarenal infusions of atrial natriuretic factor (0.3 micrograms/kg/min), which provided supraphysiological levels of atrial natriuretic factor in the renal arterial plasma, failed to attenuate hormone-induced renin release. In contrast, adenosine, a well-known inhibitor of renin release, abolished the renin release response to both hormones. These data indicate that, at the dose used in this study, synthetic atrial natriuretic factor does not act directly on the juxtaglomerular cell to attenuate hormone-induced renin release. Further, these results imply that circulating endogenous atrial natriuretic factor cannot directly attenuate juxtaglomerular cell responsiveness.
The relationship between cations and blood pressure in the People's Republic of China.
Authors: Kesteloot H , Huang D X , Li Y L , Geboers J , Joossens J V
Published: June 2012

Blood pressure was measured in the north and in the south of the People's Republic of China in 1002 men and 1006 women. The 24-hour urinary excretion of sodium, potassium, calcium, magnesium, and creatinine was measured, and the relationship between urinary cations and blood pressure was studied. Blood pressure and 24-hour sodium excretion were higher in northern China than in southern China. With some exceptions, a positive correlation was found between urinary sodium and blood pressure and a negative one between 24-hour urinary potassium excretion and blood pressure. Urinary calcium correlated negatively and urinary magnesium did not correlate significantly with blood pressure. The sodium/potassium ratio correlated positively with blood pressure, and the calcium/magnesium ratio, negatively. This study confirms the positive within-population relationship between sodium intake and blood pressure in Oriental populations.
The Influence of Injection Site upon the Form of Dye-Dilution Curves
Authors: PEARCE MORTON LEE , McKEEVER WILLIAM P. , DOW PHILIP , NEWMAN ELLIOT V.
Published: June 2012

The validity of the serial compartment analysis of dye dilution curves was tested by injecting dye into the right auricle, pulmonary artery, a pulmonary vein and the aorta consecutively while sampling blood from the carotid artery. It was found that the serial compartment analogy is valid and that the lungs are the largest volume in the series. In curves obtained by injecting into the pulmonary artery and sampling from the left auricle it was shown that under the conditions of the experiments, the lungs act like a single volume from which dye is washed out in exponential fashion.
The Genesis of the Aortic Standing Wave
Authors: ALEXANDER ROBERT S.
Published: June 2012

On the basis of observations of arterial pulse forms in anesthetized dogs, a hypothesis is developed to account for the genesis of the aortic standing wave which is responsible for the dicrotic characteristics of pulses recorded from the abdominal-femoral system. A sudden lowering of resistance to pulse wave propagation in the region of the diaphragm and an increase in resistance in the peripheral femoral bed produce reflections which, because of the equivalent wave-lengths of the thoracic and abdominal-femoral segments of the aortic system, create a resonant oscillation of the aortic blood column between the root of the aorta and the femoral bed.
Evaluation of a New Cuvette Densitometer for Determination of Cardiac Output
Authors: SHADLE OSCAR W. , FERGUSON THOMAS B. , GREGG DONALD E. , GILFORD SAUL R.
Published: June 2012

Quantitation of cardiac output by the Stewart-Hamilton method will have extended usefulness if the accuracy of measuring the concentration of Evans blue dye in whole blood is established. Cardiac outputs by this method have been compared in dogs with outputs by the rotameter and the Fick method. The constant-flow photometer (Friedlich) was used initially, but certain difficulties in its use led to the development of a new cuvette densitometer. Comparisons using both these instruments gave average variations of plus 7.0 per cent and minus 5.4 per cent from the reference methods. With proper caution cardiac outputs in dogs can be accurately obtained from dye dilution curves in whole blood.
Changes in Protein-Bound Dye Disappearance Rate as a Result of Evisceration and Nephrectomy
Authors: PALDINO RITA L. , SOSNOW MAX , HYMAN CHESTER
Published: June 2012

This study presents data which indicate that evisceration results in a marked decrease in the rate of disappearance of Evans Blue (T-1824) from the circulation of rabbits. Nephrectomy causes a significant increase in the rate of removal of dye from the blood stream. The possible explanations for these changes are considered, and the objections to the use of dye disappearance as a measure of capillary permeability are discussed.
Higher Frequency Phenomena in the Normal Ballistocardiogram
Authors: EDSON JOHN N. , DICKES ROBERT , FLAMM GERALD H. , TOBIN MICHAEL
Published: June 2012

Physiologic higher frequency phenomena may be demonstrated in ballistocardiograms from normal subjects. These phenomena consist of notches or multiple oscillations on the H-I and K-L segments of the tracings. They may be demonstrated by recording the unfiltered output of an electromagnetic direct-body ballistocardiograph. They become more prominent as the transducer is applied closer to the source of cardiovascular forces, or by passing the output of the transducer through a band pass filter. The time relationship of these oscillations to simultaneously recorded heart sounds suggests their association with the ballistics of the closing heart valves.
Hypertension Following Bilateral Nephrectomy of the Dog
Authors: MUIRHEAD E. E. , JONES F. , GRAHAM P.
Published: June 2012

Hypertension following bilateral nephrectomy of dogs has been obtained consistently in association with sodium balance and in the absence of expansion of the extracellular fluid volume as ordinarily measured. An enhanced dietary protein intake appears to be involved in the genesis of the hypertension under these conditions. Alterations in protein and potassium metabolism are described. The present, as well as former studies on the hypertension following nephrectomy, suggest that multiple factors may be involved in the pathogenesis of the hypertension. These factors are discussed.
Bradykinin, Digital Blood Flow, and the Arteriovenous Anastomoses
Authors: Burch George E. , DePasquale Nicholas P.
Published: June 2012

Bradykinin injected ipsilaterally into the brachial artery has been shown rheoplethys mographically to produce digital vascular changes which are the same as those observed in reactive hyperemia. The changes seem to be due to a selective constriction of the A-V shunts with dilatation of the arterioles, capillaries, venules, and veins. These vessels seem to dilate largely in passive response to the constriction of the A-V shunts.
Relation Between Blood Flow and Contraction Force in Active Skeletal Muscle
Authors: Hirvonen Leo , Sonnenschein Ralph R.
Published: June 2012

The relationships between blood flow and contraction force in intermittently contracting eat skeletal muscle during alterations of flow by various procedures were studied.

When flow only to the active gastrocuemiussoleus was measured, mechanical reduction in perfusion pressure, sympathetic chain stimulation and intra-arterial norepinephrine and epinephrine infusion were found to have esscritially identical effects in producing reduction in muscle force proportionate to that in blood flow. When flow in the whole leg musculature was measured while either the gastrocnemius-soleus or the quadriceps was active, varying results were obtained with these procedures which could be ascribed to differenees in response of vessels in active and resting muscles. During the carotid sinus reflex some vasoconstrictor activity occurred in active muscle. On the assumption that the maximal, muscle force is an index of the nutritional component of the flow, it may be inferred that, in general, those procedures in which total flow was restricted produced no alteration in distribution of nutritional and non-nutritional flow within the active muscle.

Blood flow and muscle force were generally unaffected by concomitant stimulation in the hypothalamus of the sympathetic vasodilator system. An increase in flow and force occasionally was observed whien these were at low levels, or when a rise in arterial pressure occurred. The sympathetic vasodilator system produces no alteration in distibution of flow and would seem to play no role in the maintenance of blood flow and performance of normal active muscle.

A fundamental difference appears to exist in the responses of the vasculature of resting and active skeletal muscle; this difference is related to the interplay of specialized effects of the vasomotor innervations and the action of vasodilator metabolites.
Mechanism of Ventricular Fibrillation in Hypothermia
Authors: Covino Benjamin G. , D'Amato Henry E.
Published: June 2012

The mechanism of ventricular fibrillation in hypothermia is best explained by the circus movement theory. The main factor responsible for the initiation of a circus movement type of fibrillation is the marked reduction in conduction velocity which is not counterbalanced by a proportional prolongation of the refractory period, in other words, an increase in the conduction time/refractory period ratio occurs. Maintenance of a fibrillary state in hypothermia is dependent also on the size of the heart. Small hearts either fail to fibrillate or show a spontaneously reversible type of fibrillation. Moreover, shortening the conduction pathway by cutting a fibrillating heart will abolish the arrhythmia. Sympathomimetic amines which increase conduction velocity and so reduce the conduction time/refractory period ratio are also capable of decreasing the incidence of fibrillation. The sequence of events which may lead to development of ventricular fibrillation in hypothermia is discussed.