bluuebunny/crossref_metadata_2025 huggingface dataset:
Orthostatic hypertension. Pathogenetic studies.
Authors: Streeten D H , Auchincloss J H , Anderson G H , Richardson R L , Thomas F D , Miller J W
Published: June 2012

Among 1800 referred hypertensive patients, 181 had recumbent diastolic blood pressures (DBP) below 90 mm Hg and standing DBP above 90 mm Hg. Orthostatic increments in DBP were greater in these orthostatic hypertensive patients than in 181 persistently hypertensive patients and 134 normotensive subjects. In 12 patients with orthostatic hypertension, the orthostatic fall in cardiac output (27.3 +/- 2.9%, measured by a respiratory method) was double that in 8 normotensive subjects (13.3 +/- 3.7%, p less than 0.01). An inflated pressure suit over the pelvis and lower limbs prevented the excessive fall in cardiac output and significantly reduced (p less than 0.02) the excessive rise in standing DBP in orthostatic hypertensive patients. Gravitational pooling of blood in the legs and reduction of blood in the head was measured by external gamma counting of autologous erythrocytes labeled with sodium pertechnetate Tc 99m through ports in fixed positions over the leg and the temple. Orthostatic intravascular pooling was significantly greater (p less than 0.01) in orthostatic hypertensive subjects than in normotensive subjects, and the magnitudes of orthostatic pooling and orthostatic increases in DBP were closely correlated (r = +0.85). Plasma norepinephrine concentrations were similar in recumbency and after sustained handgrip exercise, but significantly greater (p less than 0.01) after 5 to 60 mins of standing in orthostatic hypertensive subjects than in normotensive subjects. Our results indicate that orthostatic hypertension is common and that its mechanism in representative patients involves excessive orthostatic blood pooling, which results in decreased venous return, decreased cardiac output, increased sympathetic stimulation (presumably through low-pressure cardiopulmonary receptors), and excessive arteriolar, but not venular, constriction.
An improved fluorometric assay of rat serum and plasma converting enzyme.
Authors: Santos R A , Krieger E M , Greene L J
Published: June 2012

The most sensitive nonradiometric routine assay for angiotensin-converting enzyme (ACE) activity uses fluorometry to detect His-Leu released from Hip-His-Leu. Our results indicate that, in contrast to human serum, rat serum and plasma contain large and variable amounts of dipeptidase activity that lead to a subestimation of the ACE activity measured in 0.1 M potassium phosphate buffer, pH 8.3, containing 0.3 M NaCl, the most commonly used assay for human serum and tissue ACE. We describe and validate an assay for 1 to 10 microL rat and human serum or plasma using 5 mM Hip-His-Leu in 500 microL of 0.4 M sodium borate buffer, pH 8.3, containing 0.9 M NaC1 at 37 degrees C that reduced the subestimation error to less than or equal to 3% (rat serum) and less than or equal to 0.1% (human serum) and increased the ACE activity twofold to threefold. The Km and Vmax are reported for rat serum ACE (Hip-His-Leu) and dipeptidase (His-Leu) in borate buffer and phosphate buffer. Rat serum ACE hydrolysis of Hip-His-Leu measured by fluorometry correlated (r = 0.99, p less than 0.05) with the hydrolysis of angiotensin I measured by high-performance liquid chromatography. A direct method based on amino acid analysis is described for evaluating the dipeptidase error of complex mixtures such as tissue extracts and other physiological fluids. We have found that the assay can be used to measure ACE activity in 25 samples (in duplicate) in 2 hours with small intraassay (2.2%) and interassay (3.9%) coefficients of variation.(ABSTRACT TRUNCATED AT 250 WORDS)
Direct versus indirect pressor and vasoconstrictor actions of angiotensin in conscious dogs.
Authors: Fujii A M , Vatner S F
Published: June 2012

To determine the importance of the direct and the indirect pressor and vasoconstrictor actions of angiotensin II (ANG II), experiments were conducted in conscious dogs 2 to 8 weeks after instrumentation with aortic catheters and aortic electromagnetic flow probes to measure arterial pressure and cardiac output. Total peripheral resistance was calculated by an on-line digital computer. Pretreatment with propranolol eliminated complicating inotropic effects of norepinephrine, released by the indirect actions of ANG II. The pressor and vasoconstrictor responses after ganglionic blockade, in either the presence or absence of arterial baroreceptor nerves, were considered to be the direct effects of ANG II. In conscious dogs, systemically administered ANG II (32 ng/kg bolus) increased mean arterial pressure by 38 +/- 3 mm Hg, total peripheral resistance by 37 +/- 2 mm Hg/L/minute, and decreased heart rate by 15 +/- 2 beats/minute. After arterial baroreceptor denervation, administration of ANG II increased mean arterial pressure by 88 +/- 7 mm Hg, total peripheral resistance by 54 +/- 4 mm Hg/L/minute, and heart rate by 12 +/- 2 beats/minute. After arterial baroreceptor denervation and ganglionic blockade with hexamethonium, administration of ANG II increased mean arterial pressure by 53 +/- 8 mm Hg, total peripheral resistance by 27 +/- 3 mm Hg/L/minute, and left heart rate unchanged. These results indicate that in the conscious dog without baroreflex buffering nearly one-half of the pressor and vasoconstrictor actions of angiotensin are not direct, but are mediated by the autonomic nervous system.
Effects of antiglucocorticoids on glucocorticoid hypertension in the rat.
Authors: Grünfeld J P , Eloy L , Moura A M , Ganeval D , Ramos-Frendo B , Worcel M
Published: June 2012

The early phase of hypertension induced in rats by a glucocorticoid agonist RU 26988 was studied. Systolic blood pressure increased by 35 mm Hg. Water and sodium urinary excretion increased transiently, and plasma volume decreased. Total and ouabain-sensitive sodium efflux, as well as rubidium efflux, were enhanced by glucocorticoid administration. Low salt intake did not prevent hypertension. Pretreatment with RU 38486, a steroid with antiglucocorticoid properties, largely prevented the rise in blood pressure (+10 mm Hg) and suppressed transient natriuresis and the decrease in plasma volume. Changes in total and ouabain-sensitive sodium efflux were completely prevented, whereas changes in rubidium efflux were only partly reversed. Similarly, administration of progesterone, a steroid with antiglucocorticoid effects, prevented glucocorticoid hypertension (+11 mm Hg) and vascular ionic changes. In contrast administration of RU 28318, an antimineralocorticoid agent, was without effect on glucocorticoid hypertension (+38 mm Hg). Progesterone or RU 38486 administered after glucocorticoid also decreased blood pressure. Present data indicate that glucocorticoid hypertension may be prevented or reversed in its early phase by steroid drugs with antiglucocorticoid properties. These drugs also appeared to prevent the sodium and rubidium flux abnormalities induced by glucocorticoid. We suggest that activation of the vascular glucocorticoid receptors may be involved in the pathophysiology of glucocorticoid hypertension.
Cardiovascular profile and hypotensive mechanism of ketanserin in the rabbit.
Authors: Bolt G R , Saxena P R
Published: June 2012

Using the radioactive microsphere technique, we studied the systemic and regional hemodynamic effects of ketanserin in conscious renal hypertensive rabbits. To characterize the hypotensive mechanism of the compound, we evaluated its antagonism toward 5-hydroxytryptamine2 and alpha 1-adrenergic receptors at hypotensive doses and compared the cardiovascular profile of ketanserin with that of the alpha 1-selective adrenergic receptor antagonist prazosin. Ketanserin (0.1, 0.3, and 1.0 mg/kg i.v.) produced a biphasic effect on the arterial blood pressure. A short, pronounced fall in blood pressure accompanied by tachycardia preceded a more moderate and longer lasting dose-related hypotensive effect. The presence of adequate autonomic nervous system activity seems to be required for the prolonged hypotensive action of ketanserin because, in animals pretreated with hexamethonium (30 mg/kg), the blood pressure, after an initial decrease, returned to baseline values within a few minutes after each ketanserin dose. Ketanserin inhibited the pressor responses produced by 5-hydroxytryptamine (10, 30, and 100 micrograms/kg i.v.) and phenylephrine (3, 10, and 30 micrograms/kg i.v.), which indicates that, at hypotensive doses, the compound antagonized both 5-hydroxytryptamine2 receptors and alpha 1-adrenergic receptors. At doses that caused a comparable degree of alpha 1-adrenergic receptor blockade, ketanserin (0.1, 0.3, and 1.0 mg/kg i.v.) as well as prazosin (0.01, 0.03, and 0.10 mg/kg i.v.) decreased the blood pressure as a result of a reduction in total peripheral resistance. While cardiac output increased, especially at the lower doses of ketanserin, a moderate decrease in this variable contributed to the hypotensive effect of the highest dose of prazosin. Both compounds decreased the vascular resistance in the kidneys, gastrointestinal tract, and bones, whereas that in the skin and skeletal muscles was not significantly altered. In contrast to prazosin, ketanserin also caused vasodilatation in the coronary and cerebral vascular beds.(ABSTRACT TRUNCATED AT 250 WORDS)
Sodium is more important than calcium in essential hypertension.
Authors: MacGregor G A
Published: June 2012

There is much circumstantial and some direct evidence in humans to suggest that a high consumption of salt predisposes communities and individuals to the development of essential hypertension. Recent work has suggested possible mechanisms whereby a high salt intake could cause a rise in blood pressure in genetically susceptible persons. Restriction of salt intake in the diet lowers blood pressure in many subjects with high blood pressure and this fall in blood pressure is mediated in part by a diminished renin response to sodium restriction as hypertension develops. The effect of sodium restriction, like diuretics, is additive to most blood pressure lowering drugs, particularly those that inhibit the renin system such as beta-blockers and angiotensin converting enzyme inhibitors. Claims that a slight reduction in calcium intake may be important in the development of high blood pressure are disputed. Furthermore, no satisfactory hypothesis has been put forward to explain how a small reduction in dietary calcium intake could cause high blood pressure. Large increases in calcium intake have been reported to lower blood pressure in both normotensive and hypertensive humans. The three published studies, however, are not in agreement.
Insulin and blood pressure in obesity.
Authors: Lucas C P , Estigarribia J A , Darga L L , Reaven G M
Published: June 2012

To assess factors in overweight persons that account for a tendency toward hypertension, 33 very obese women, 26 to 77 years of age, were studied. Blood pressures in these 33 women varied from low normal to mildly hypertensive. None of them had taken medication for high blood pressure, and none had diabetes mellitus. The effect of independent variables--age, body mass index (weight/height2), fasting serum glucose levels, fasting serum insulin levels, and 24-hour urinary sodium excretion--on systolic and diastolic blood pressure was assessed. There was no correlation between sodium excretion and blood pressure. Age did not correlate with diastolic blood pressure but did correlate with systolic blood pressure when body mass index, serum glucose level, and insulin level were controlled. Diastolic blood pressure correlated with body mass index and serum glucose level, but only the latter remained significant when all independent variables were considered together. Both systolic and diastolic blood pressure were found to be significantly related to fasting serum insulin level (r = 0.47, p = 0.005 and r = 0.68, p less than 0.001) even when age, weight, and serum glucose level were controlled (r = 0.41, p = 0.025 and r = 0.62, p less than 0.001 respectively). The relation between serum insulin and blood pressure was more pronounced in those women with a family history of hypertension. These data indicate that insulin may play a major role in the regulation of blood pressure in obesity and that the previously accepted relation of weight to blood pressure may depend on blood levels of insulin.
Maternal effects on blood pressure and survivability in inbred Dahl salt-sensitive rats.
Authors: Dene H , Rapp J P
Published: June 2012

Maternal effects on blood pressure response to high salt diet were evaluated using inbred Dahl salt-sensitive (S/JR) and inbred Dahl salt-resistant (R/JR) rats. A cross-fostering experiment did not yield any evidence for a consistent effect of strain-specific fostering environments on the subsequent blood pressure response of S/JR or R/JR rats. A small increment in blood pressure seen only in male rats associated with the maternal R/JR environment was probably the result of effects mediated through an increment in body weight. In an experiment in which litter size was varied, weaning body weight was found to be an important predictor of survivability of S/JR rats fed a high salt (8% NaCl) diet; higher body weight was associated with longer survival in both males and females. Higher body weight at weaning also was associated with a small increment in blood pressure of S/JR rats in male, but not in female, rats. Intrauterine environment was evaluated using the embryo transplant technique. No evidence for a difference between S/JR and R/JR intrauterine environments with regard to blood pressure response of S/JR pups to salt was found. It is concluded that the early nutritional level during nursing as altered by varying litter size has important effects on body weight and survivability of S/JR rats on high salt diet, but that these effects are not mediated through changes in blood pressure. We found no evidence for genetic effects on blood pressure operating through the early maternal intrauterine or fostering environments.
Nonproportional changes in plasma renin concentration, renal renin content, and rat renin messenger RNA.
Authors: Nakamura N , Soubrier F , Menard J , Panthier J J , Rougeon F , Corvol P
Published: June 2012

The expression of the renin gene in rat kidneys was studied using mouse submaxillary gland renin complementary DNA. The length of rat renin messenger RNA (mRNA) was approximately 1600 nucleotides, similar to that of mouse submaxillary gland and kidney renin mRNA. Rat renin mRNA was quantified by a radiodensitometric complementary DNA hybridization assay. The effects of intense long-term stimulation and short-term inhibition of renin secretion on plasma renin concentration, renal renin concentration, and renin mRNA content were compared with those of controls. After 15 days of sodium depletion and captopril treatment, plasma renin concentration increased 46-fold, renal renin concentration only 1.5-fold, and renin mRNA content increased about threefold. Following a 1-hour infusion of angiotensin II in sodium-depleted and captopril-treated rats, plasma renin concentration decreased by 84% whereas no significant changes in either renal renin concentration or renin mRNA content were observed. These results show that sodium depletion and captopril treatment increase the level of renin gene transcription and renin biosynthesis. However, there are nonproportional changes in plasma renin levels, renal renin content, and its mRNA. These results suggest that newly synthesized renin is not stored in the kidney but is rapidly secreted into the blood. Short-term inhibition of plasma renin concentration by angiotensin II is most likely mediated by posttranslational mechanisms.
Role of angiotensin II in renal wrap hypertension.
Authors: Denton K M , Anderson W P
Published: June 2012

The role of angiotensin II in the development of renal wrap hypertension was studied in rabbits that underwent either bilateral renal cellophane wrap or sham operation. In half the rabbits, angiotensin II production was blocked by continuous administration of enalapril. Four weeks after renal wrapping, mean arterial pressure had risen by 48 +/- 5 mm Hg in untreated rabbits, but by only 25 +/- 4 mm Hg in enalapril-treated rabbits (p less than 0.01). Similar differences were also measured 6 weeks after wrapping. In untreated rabbits, plasma renin activity had increased fourfold 4 and 6 weeks after renal wrapping. There were no significant changes in blood pressure or plasma renin activity following sham operation. Compared with that in sham-operated rabbits, renal blood flow was reduced by 60% in the untreated rabbits 4 weeks after wrapping but by only 30% in the enalapril-treated wrapped rabbits (p less than 0.05). Renal vascular resistances were 5.5 +/- 1.7 mm Hg . ml-1 . min-1 and 1.2 +/- 0.1 mm Hg . min . ml-1 in the untreated wrapped and sham-operated rabbits respectively and 1.9 +/- 0.4 mm Hg . min . ml-1 and 0.8 +/- 1 mm Hg . min . ml-1 in the enalapril-treated wrapped and sham-operated rabbits. Renal wrapping did not alter filtration fraction in untreated rabbits, but markedly reduced it in enalapril-treated rabbits. These results suggest that angiotensin II had two major effects in rabbits after bilateral renal wrapping: it contributed substantially to the increase in blood pressure and caused renal vasoconstriction, primarily at a postglomerular site.
Persistence of high diastolic blood pressure in thin children. The Bogalusa Heart Study.
Authors: Burke G L , Freedman D S , Webber L S , Berenson G S
Published: June 2012

Relationships between initial anthropometric variables and subsequent diastolic blood pressure (fourth phase) were examined in children identified as being in the upper quintile for diastolic blood pressure at Year 1. Of 156 white children, aged 10 to 14 years, with diastolic blood pressure levels in the upper age-race-sex-specific quintile at Year 1, 38% remained in the upper quintile at Year 4. However, there was a definite trend for leaner children, defined by ponderosity (weight/height3) to remain in the highest diastolic blood pressure quintile (p less than 0.001). Of white children originally identified in the highest quintile for diastolic blood pressure and the lowest quintile for ponderosity (lean group), 67% (18 of 27) remained in the upper quintile at Year 4. In contrast, only 21% (11 of 52) of white children identified as being in the highest quintile for both diastolic blood pressure and ponderosity (obese group) at Year 1 were in the upper diastolic blood pressure quintile at Year 4. Similar results were seen in children examined 5 years later. Pearson correlation coefficients and linear regression analyses confirmed the negative relationship between initial ponderosity and subsequent diastolic blood pressure, especially in older children. A similar relationship was noted in black children. Potential differences in the etiological process of obesity-related and non-obesity-related high blood pressure were examined. These observations indicate that characteristics other than obesity can contribute to high blood pressure in late childhood.
Modulation of kidney renin messenger RNA levels during experimentally induced hypertension.
Authors: Moffett R B , McGowan R A , Gross K W
Published: June 2012

Several experimental procedures produce dramatic alterations in kidney renin production, leading to increased plasma renin levels with attendant hypertension in animal model systems. The pattern of changes for kidney renin messenger RNA (mRNA) levels relative to changes for tissue and plasma renin activity was studied in Sprague-Dawley rats made hypertensive by either coarctation of the aorta between the two renal arteries or clipping of the left renal artery. In both models, the renin mRNA content of the contralateral hypertrophied kidney transiently decreased to undetectable levels while the ischemic kidney exhibited transient increases in renin mRNA. In aorta-coarctated rats ischemic kidney renin mRNA increased 10-fold to 16-fold during the first 3 days after coarctation but returned to the level observed in sham-operated rats 14 days after operation. However, differences between the time course and magnitude of changes in renin mRNA levels and the pattern of alteration in tissue and plasma renin activities were observed. Thus, although the kidney renin mRNA transiently increased in hypertensive animals, the extent of this increase was insufficient to account for the 30-fold to 50-fold increases in plasma renin activity. Similarly, the transient increase in kidney renin mRNA was inconsistent with only a twofold increase in tissue renin enzyme activity of the ischemic kidney. These data indicate that in addition to alterations in the kidney renin mRNA pool, posttranslational processing and/or release of renin from the kidney are cocontributors in regulating the plasma renin levels in these experimental models.
Prolonged administration of human atrial natriuretic peptide in healthy men. Reduced aldosteronotropic effect of angiotensin II.
Authors: Vierhapper H , Nowotny P , Waldhäusl W
Published: June 2012

The effect of angiotensin II (5, 10, 20 ng/kg/min) on blood pressure and on the plasma concentrations of aldosterone was studied in six healthy men with and without the concomitant administration of synthetic human atrial natriuretic peptide given 1) as an i.v. bolus of 25 micrograms followed by a 6-hour infusion of 25 micrograms/hr or 2) as an i.v. bolus of 175 micrograms followed by a 6-hour infusion of 100 micrograms/hr. The pressor effect of angiotensin II (i.e., the rise of mean blood pressure above individual basal levels) remained unchanged during the administration of both doses of human atrial natriuretic peptide. The angiotensin II-induced rise in plasma concentrations of aldosterone in terms of absolute values) was reduced by human atrial natriuretic peptide during both trials. The rise in plasma concentrations of aldosterone above individual basal concentrations was also reduced during the administration of human atrial natriuretic peptide, although this effect was only marginal during the low dose experiment. These effects of human atrial natriuretic peptide support the contention that its therapeutic impact in hypertensive patients might be mediated in part by a reduction of high aldosterone concentrations.
Suppression of adrenal renin in Dahl salt-sensitive rats.
Authors: Baba K , Mulrow P J , Franco-Saenz R , Rapp J P
Published: June 2012

We previously showed that adrenal renin is highest in the rat zona glomerulosa (ZG) and that low sodium or high potassium and nephrectomy increase adrenal ZG renin and aldosterone. Dahl salt-sensitive rats (S) have been shown to have lower plasma renin activity and plasma aldosterone and higher plasma 18-hydroxy-11-deoxycorticosterone than Dahl salt-resistant rats (R). In this study we assess the possible role of adrenal ZG renin in the suppression of aldosterone in S rats. Adrenal ZG renin was significantly decreased in S as compared with R rats even at 6 weeks of age, when both S and R rats are still normotensive (S = 7.2 +/- 0.2, R = 18.0 +/- 1.6 ng angiotensin I/mg protein/hr). Adrenal ZG aldosterone was also significantly lower in S than in R rats (S = 21.1 +/- 4.3, R = 39.5 +/- 3.6 ng/mg protein). Furthermore, the rise in adrenal ZG renin and aldosterone after nephrectomy in S rats was significantly less than that in R rats. To determine if the suppressed adrenal ZG renin of S rats is due to volume expansion, we studied the effect of a sodium-deficient diet on adrenal ZG renin in S and R rats. After 2 weeks of a sodium-deficient diet S rats had significantly lower basal adrenal ZG renin than did R rats (S = 7.6 +/- 0.4, R = 21.7 +/- 1.9 ng angiotensin I/mg protein/hr) and a marked blunting of the adrenal ZG renin response to nephrectomy (S = 13.6 +/- 1.1, DR = 167 +/- 16.1 ng angiotensin I/mg protein/hr).(ABSTRACT TRUNCATED AT 250 WORDS)
Venous abnormality in normotensive young men with a family history of hypertension.
Authors: Ito N , Takeshita A , Higuchi S , Nakamura M
Published: June 2012

Maximal vasodilator capacity of resistance vessels has been shown to be reduced in normotensive young men with a family history of hypertension. The present study attempted to examine whether venous distensibility is decreased in normotensive men with hypertensive relatives. The venous pressure-volume relationship was determined in the forearm with a water-filled plethysmograph in 17 normotensive young men with hypertensive relatives (mean blood pressure, 85 +/- 2 [SE] mm Hg; age, 22 +/- 1 years) and 18 young men with no family history of hypertension (mean blood pressure, 81 +/- 2 mm Hg; age, 22 +/- 1 years). The venous pressure-volume curve in men with hypertensive relatives as compared to that in men with no family history of hypertension was shifted toward the pressure axis (p less than 0.001). This findings suggests that venous distensibility is decreased in normotensive young men with hypertensive relatives. Administration of phentolamine, 1 mg/min i.v. for 5 minutes, did not alter venous distensibility, and venous distensibility after phentolamine administration was less in men with hypertensive relatives than in men with no family history (p less than 0.001), which suggests that decreased venous distensibility found in normotensive young men with hypertensive relatives was unlikely to be related to alpha-adrenergic mechanisms. These results suggest that normotensive young men with a family history of hypertension have vascular abnormalities that involve veins as well as arteries.
Captopril modifies the hemodynamic and neuroendocrine responses to sodium nitroprusside in hypertensive patients.
Authors: Clementi W A , Durst N L , McNay J L , Keeton T K
Published: June 2012

To determine if clinically effective doses of the antihypertensive agent captopril affected the neuronal release of norepinephrine or baroreflex sensitivity, changes in plasma norepinephrine concentration and heart rate were related to the changes in mean arterial pressure seen during the intravenous infusion of stepwise incremental doses of sodium nitroprusside before and during captopril treatment in eight hypertensive men with normal or low plasma renin activity. At all times, significant linear correlations were found between the decrease in mean arterial pressure and the dose of sodium nitroprusside, the increase in heart rate and the decrease in mean arterial pressure, and the increase in plasma norepinephrine concentration and the decrease in mean arterial pressure. When the subjects were treated with captopril (25 mg t.i.d.) for 2 to 4 weeks, supine mean arterial pressure decreased from 130 to 114 mm Hg (-12%; p less than 0.05), heart rate did not change, supine and upright plasma renin activity increased, while supine plasma norepinephrine and epinephrine concentration decreased slightly. Therapy with captopril (25 mg t.i.d.) increased baroreflex sensitivity, as assessed by the slope of the regression line relating the increase in heart rate to the decrease in mean arterial pressure, and increased the responsiveness of the sympathetic nervous system, as assessed by the slope of the regression line relating the increase in plasma norepinephrine concentration to the decrease in mean arterial pressure. These increases were accompanied by a decrease in the slope of the regression line relating the decrease in mean arterial pressure to the dose of sodium nitroprusside and thus were associated with a decreased sensitivity to the vasodepressor effects of sodium nitroprusside.(ABSTRACT TRUNCATED AT 250 WORDS)
Innovative blood pressure measurements yield information not reflected by sitting measurements.
Authors: Jorde L B , Williams R R
Published: June 2012

A study of 873 healthy adults and children from Utah kindreds was performed to identify redundant and unique information contained in multiple diverse blood pressure determinations. Systolic blood pressure, fourth-phase and fifth-phase diastolic blood pressures, and simultaneous heart rates were measured in subjects sitting, standing, supine, and tilting, during half-maximal handgrip exercise, and just before blood drawing. A correlation matrix of 57 blood pressure and pulse variables in 618 healthy adults was analyzed. Factor analysis of the correlation matrix showed that all systolic blood pressures loaded as a single factor, accounting for 44% of the total variance of the observed variables. All heart rates also loaded together as a single factor. Diastolic blood pressures showed much more heterogeneity of information distributed among five separate factors. The same basic factors were found in young adults (age, 18-35 years) and older adults (age, 36 + years). Children under 12 years of age showed very different factor patterns, and youths 12 to 17 years of age showed patterns intermediate between those of adults and children. In light of recent clinical trials, better definitions are being sought for hypertension. Information from blood pressures other than sitting determinations may improve the definition of hypertension or better predict which patients have the highest risk of hypertension and its cardiovascular complications.
Adrenocorticotropin responses to corticotropin releasing factor and vasopressin in spontaneously hypertensive rats.
Authors: Hattori T , Hashimoto K , Ota Z
Published: June 2012

The effects of exogenous corticotropin releasing factor and arginine vasopressin were evaluated in 6- and 11-week-old spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Basal adrenocorticotropic hormone (ACTH) and vasopressin levels did not differ between SHR and WKY, but basal corticosterone level was higher in 6-week-old SHR (p less than 0.01). To block endogenous corticotropin releasing factor secretion and nonspecific systemic responses, both groups were pretreated with chlorpromazine, morphine, and sodium pentobarbital anesthesia before measurement of ACTH responses to corticotropin releasing factor and vasopressin infusion. Basal ACTH level was lower in anesthetized 6-week-old SHR than in age-matched WKY (p less than 0.01), but no difference was seen between 11-week-old WKY and SHR. The ACTH response to corticotropin releasing factor in 6-week-old WKY was significantly greater than that in age-matched SHR (p less than 0.01), whereas in 11-week-old SHR and WKY the response was similar. Compared with responses in WKY, SHR showed an increased ACTH response to high doses of vasopressin (0.25 micrograms/100 g body weight) at both ages (p less than 0.05). These results indicate that the ACTH response to corticotropin releasing factor is blunted in the early stages of hypertension in SHR but later recovers. These abnormal responses to corticotropin releasing factor and vasopressin may be related to the development of spontaneous hypertension.
Specific measurement of angiotensin metabolites and in vitro generated angiotensin II in plasma.
Authors: Nussberger J , Brunner D B , Waeber B , Brunner H R
Published: June 2012

Combining high-performance liquid chromatography with radioimmunoassay enabled the precise measurement of different angiotensins and their metabolites in plasma. Peptides were extracted from 2 ml of plasma by reversible adsorption to phenylsilyl-silica, separated by isocratic high-performance liquid chromatography, and quantitated by radioimmunoassay using a sensitive but suitably cross-reacting angiotensin II antiserum. For the C-terminal angiotensin II metabolites (2-8)heptapeptide, (3-8)hexapeptide, and (4-8)pentapeptide, overall recoveries of 10 fmol peptide added to 1 ml of plasma were (mean +/- SD), 74 +/- 6, 68 +/- 8, and 67 +/- 11%, respectively. The detection limit for these peptides in plasma was 0.2 fmol/ml. Blanks were below the detection limits. In eight seated normal subjects treated for 4 days with enalapril, 20 mg p.o., q.d., angiotensin II metabolites tended to decrease during the 4 postdrug hours. However, their cumulated concentration in relation to octapeptide increased from 54 to 163% on Day 1 and from 62 to 103% on Day 4. After 4 hours of converting enzyme inhibition with enalapril there was still a close correlation between plasma renin activity and angiotensin-(1-8)octapeptide level (r = 0.83, p less than 0.05) and between blood angiotensin I and angiotensin-(1-8)octapeptide levels (r = 0.86, p less than 0.01). Adding angiotensin I in vitro raised the angiotensin-(1-8)octapeptide levels after incubation at 4 degrees C for 4 hours. Thus, immunoreactive "angiotensin II" does not disappear after converting enzyme inhibition largely because of the cumulated contribution of cross-reacting metabolites and partly because of in vitro generation of true angiotensin II.
Leukocyte ionized calcium and sodium content and blood pressure in humans.
Authors: Bing R F , Heagerty A M , Jackson J A , Thurston H , Swales J D
Published: June 2012

The relationship between leukocyte ionized calcium concentration, sodium content, and blood pressure was studied in normotensive subjects with (n = 17) and without (n = 21) a family history of hypertension and in untreated patients with essential hypertension (n = 22). There was a highly significant correlation between intracellular ionized calcium and mean supine blood pressure (measured on the same occasion) in normal subjects with no family history of hypertension (r = +0.73, p less than 0.01). This relationship was lost in normal subjects with a family history of hypertension, and in hypertensive patients there was a nonsignificant negative correlation between intracellular ionized calcium and blood pressure (r = +0.08 and -0.31, respectively). Intracellular ionized calcium was similar in the normotensive groups (both, 126 +/- 7 nmol/L) and slightly but nonsignificantly elevated in hypertensive patients (143 +/- 10 nmol/L; p = 0.09). There was no correlation between intracellular ionized calcium and sodium content in any group (r less than 0.1). These results indicate that while leukocyte ionized calcium in normotensive subjects with no family history of hypertension may reflect smooth muscle contractility resulting in the positive correlation between leukocyte ionized calcium and blood pressure, this relationship is lost in hypertensive patients and subjects predisposed to hypertension. This may be due to an altered relationship between leukocyte and smooth muscle calcium handling in these subjects or to non-calcium-mediated influences on blood pressure.
Enhanced DNA synthesis in heart and kidney of newborn spontaneously hypertensive rats.
Authors: Walter S V , Hamet P
Published: June 2012

Studies comparing relative organ weight (per gram of body weight) in spontaneously hypertensive rats (SHR) and their normotensive controls, Wistar-Kyoto rats (WKY), have shown that the heart and kidney of SHR are enlarged at birth. In addition, higher DNA concentrations in these organs provide evidence of cardiac and renal cellular hyperplasia in newborn SHR. The rate of DNA synthesis was estimated with [methyl-3H]thymidine labeling in vivo for heart, kidney, liver, adrenals, and aorta of newborn WKY and SHR, and significantly higher relative organ weights, protein levels, and DNA contents were observed only for heart and kidney from SHR. In contrast, relative weight was significantly lower for liver from SHR and the same for adrenals from WKY and SHR despite lower adrenal protein and DNA contents for SHR. Relative weight and protein content of aorta were higher in SHR, possibly indicating hypertrophy of this organ. Several differences in [methyl-3H]thymidine labeling were observed in organs from SHR. Significantly higher organ accumulation (cpm/mg organ weight) was observed for heart from SHR (p less than 0.01), and higher incorporation into DNA (cpm/cpm) was observed for kidney and liver from SHR (p less than 0.001). Most significant was the finding of higher DNA specific activity for heart (+33%; p less than 0.05) and kidney (+39%; p less than 0.001) from SHR. These data provide evidence of enhanced DNA synthesis in the heart and kidney of newborn SHR.
Identification of renin and angiotensinogen messenger RNA sequences in mouse and rat brains.
Authors: Dzau V J , Ingelfinger J , Pratt R E , Ellison K E
Published: June 2012

Components of the renin angiotensin system have been demonstrated in mouse and rat brains. However, local synthesis of renin has not been documented. In this study, we employed mouse submandibular gland renin complementary DNA (pDD-1D2) and rat liver angiotensinogen complementary DNA (pRang3) to examine whether renin and angiotensinogen RNA sequences exist in mouse and rat brain. Angiotensinogen messenger RNA sequences were readily demonstrable in whole rat and mouse brain using Northern blot hybridization analysis. Using large quantities (greater than 100 micrograms) of brain total RNA and the sensitive complementary RNA probe, we were able to detect low levels of renin RNA sequences in the brains of both species. The relatively low concentration of brain renin messenger RNA and high concentration of angiotensinogen messenger RNA raises several interesting questions about the distribution of these two proteins and their relative contribution to activity of the brain renin-angiotensin system. In summary, our data demonstrate the expression of both renin and angiotensinogen genes in mouse and rat brains and provide definitive evidence for an independent endogenous brain renin angiotensin system.
Vascular renin-angiotensin system in two-kidney, one clip hypertensive rats.
Authors: Okamura T , Miyazaki M , Inagami T , Toda N
Published: June 2012

The possible role of the renin-angiotensin system in the maintenance of hypertension in two-kidney, one clip hypertensive rats was studied. Plasma renin activity rose rapidly and markedly in association with the elevation of blood pressure and then decreased gradually, although blood pressure remained high. Renin activity in the lung, aorta, and mesenteric artery also increased with the development of hypertension and then decreased in a way similar to that of plasma renin activity at the chronic stage of hypertension. Plasma angiotensin converting enzyme activity did not change significantly until 16 weeks after unilateral renal artery clipping, whereas vascular angiotensin converting enzyme activity significantly increased at the chronic, but not the acute, stage of hypertension. In chronically renal hypertensive rats, 1-sarcosine, 8-isoleucine angiotensin II or enalapril, an angiotensin converting enzyme inhibitor, lowered the blood pressure and enalapril also lowered the angiotensin converting enzyme activity of vascular tissues. The constrictor effect of angiotensin I was greater in isolated arteries from chronically hypertensive rats than in those from age-matched normotensive rats. These results suggest that the vascular renin-angiotensin system plays an important role in the maintenance of two-kidney, one clip hypertension. Elevated vascular angiotensin converting enzyme activity appears to increase local production of angiotensin II, which results in vasoconstriction by acting directly and indirectly through adrenergic nerves on vascular smooth muscle.
Plasma digitalislike activity in essential hypertension or end-stage renal disease.
Authors: Deray G , Pernollet M G , Devynck M A , Zingraff J , Touam A , Rosenfeld J , Meyer P
Published: June 2012

Plasma extracts from 119 subjects showed a digitalislike activity, as evidenced by the ability of these extracts to inhibit ouabain binding to the Na+-K+ pump. High levels of the digitalislike compound were found in 18 of 54 untreated hypertensive subjects, 7 of 21 normotensive subjects with a family history of hypertension, and 10 of 14 patients with end-stage renal failure. Dialysis significantly reduced the activity of this compound. These results suggest 1) that endogenous digitalislike factor is not directly linked to hypertension but rather is related to sodium balance and 2) that it neither originates nor is activated by renal tissue, as it was present in four of six anephric patients.
Peripheral pressor systems in hypertension caused by nucleus tractus solitarius lesions.
Authors: Sved A F
Published: June 2012

The roles of vasopressin, the sympathoadrenal system, and the renin-angiotensin system in the production of hypertension after bilateral destruction of the nucleus tractus solitarius (NTS) were examined in chloralose-anesthetized rats. Since the activity of the renin-angiotensin system is high in anesthetized rats, additional studies were performed in unanesthetized, freely moving rats to evaluate the role of the renin-angiotensin system in hypertension caused by NTS lesions. Hypertension produced by bilateral electrolytic NTS lesions in rats was accompanied by elevated plasma levels of vasopressin (approximately 7-fold), norepinephrine (greater than 10-fold), and epinephrine (greater than 10-fold), but not of plasma renin activity. These results suggest that this form of hypertension is due to increased sympathoadrenal activity and increased vasopressin release into plasma and that the renin-angiotensin system is not involved. In rats with NTS lesions, blockade of vasopressin or the sympathoadrenal system, but not the renin-angiotensin system, elicited an acute decrease in arterial pressure. However, blockade of either vasopressin or the autonomic nervous system before production of the lesions had no effect on the resulting hypertension, indicating that in the absence of either one of these systems bilateral NTS lesions still result in severe hypertension. Although the renin-angiotensin system does not normally contribute to this hypertension, it does appear to contribute to the elevation in blood pressure once the actions of vasopressin have been blocked. In rats pretreated with a vasopressin antagonist, plasma renin activity increased following NTS lesions and the angiotensin converting enzyme inhibitor captopril decreased blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
Insulin as a potential factor influencing blood pressure in amputees.
Authors: Rose H G , Yalow R S , Schweitzer P , Schwartz E
Published: June 2012

War-injured, bilateral above-knee amputees are known to be at increased risk for cardiovascular mortality. To evaluate possible risk factors, we compared blood pressures and plasma glucose and insulin responses to orally administered glucose in 19 above-knee amputees from the Vietnam War (mean age, 36 +/- 1 years) with those of 12 age-matched unilateral below-elbow amputees. Body composition by densitometry and maximal oxygen consumption during arm or leg exercise were also determined. Nine of 19 leg amputees were hypertensive compared with one of 12 arm amputees. Their 3-hour average insulin responses were markedly increased (260 +/- 60 microU/ml) compared with those of normotensive leg (125 +/- 24 microU/ml) and arm amputees (101 +/- 20 microU/ml), and their mean body fat content (37.2%) also was elevated compared with that in both of these groups (23.2 and 22.6%, respectively). A unique finding was that both insulin response and body fat content were strongly and independently correlated with diastolic blood pressure (r = 0.55, p less than 0.01, and r = 0.62, p less than 0.01, respectively). We conclude that insulin may be a major factor in blood pressure regulation in the maturity-onset obesity that develops following traumatic leg amputation in young, healthy men.
Role of renal alpha 2-adrenergic receptors in spontaneously hypertensive rats.
Authors: DiBona G F , Sawin L L
Published: June 2012

To identify a physiological role for renal alpha 2 adrenergic receptors, renal vascular and tubular responses to administration of graded frequencies of renal nerve stimulation or graded doses of adrenergic agonists were determined in anesthetized spontaneously hypertensive, Wistar-Kyoto, and Sprague-Dawley rats. Renal vasoconstrictor responses to renal nerve stimulation and alpha 1-adrenergic receptor agonists (norepinephrine, phenylephrine) were inhibited by an alpha 1-adrenergic receptor antagonist (prazosin) but not by an alpha 2-adrenergic receptor antagonist (rauwolscine). A semilog plot of renal vasoconstrictor responses a fraction of control renal blood flow versus agonist dose (in nanograms) was linear with the slope, k, taken as the fractional decrease in renal blood flow per nanogram. The alpha 2-adrenergic receptor agonists (clonidine, guanabenz) produced minimal renal vasoconstrictor responses (fractional decrease in renal blood flow per nanogram: norepinephrine, 0.011; phenylephrine, 0.003; clonidine, 0.00087; guanabenz, 0.000037). The small renal vasoconstrictor responses to clonidine and guanabenz were more inhibited by rauwolscine than by prazosin. Low frequency renal nerve stimulation produced antidiuresis and antinatriuresis without decreasing glomerular filtration rate or renal blood flow. The antidiuretic and antinatriuretic responses were inhibited by prazosin but unaffected by rauwolscine. The magnitude of the renal vascular and tubular responses and their adrenergic receptor mediation were not different between spontaneously hypertensive, Wistar-Kyoto, and Sprague-Dawley rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Primary hypertension in a colony of dogs.
Authors: Tippett F E , Padgett G A , Eyster G , Blanchard G , Bell T
Published: June 2012

A 5-year-old female Siberian husky that was diagnosed as an essential hypertensive was bred several times over a 5-year period, producing a colony of 39 offspring. Thirty of the 39 animals were subjected to biweekly systemic arterial blood pressure determinations with femoral arterial puncture and were placed into two hypertensive and two normotensive groups based on mean blood pressure: Group 1 (mean blood pressure, 128 +/- 12 mm Hg), Group 2 (mean blood pressure, 121 +/- 3 mm Hg), Group 3 (mean blood pressure, 114 +/- 8 mm Hg), and Group 4 (mean blood pressure, 101 +/- 9 mm Hg). Groups 1, 2, and 3 had mean blood pressures significantly higher than that of Group 4 (p less than 0.05). Ten dogs (representatives from Groups 1, 2, and 3) were subjected to more detailed clinical testing including angiography, echocardiography, ophthalmic examination, plasma catecholamine and renin activity measurements, plasma lead and cadmium determinations, cerebrospinal fluid examination, renal profile, and serum chemistry and hematological analysis. Five unrelated normotensive Siberian huskies were compared with colony dogs by using echocardiography. Groups 1 and 2 showed a clear but statistically insignificant upward trend in left ventricular wall thickness indexed against body weights when compared with that in Group 3 and in the unrelated five normal Siberian dogs. Thus, the only specific difference from group to group in the colony at the termination of this study was the difference in mean blood pressure. Based on these data, it is possible and likely that aging will reveal changes secondary to chronic primary hypertension. The pathogenesis of this hereditary disorder remains unknown.