bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasma prorenin in humans and dogs. Species differences and further evidence of a systemic activation cascade.
Authors: Wilczynski E A , Osmond D H
Published: June 2012

We have studied the dog as a potential model for the human plasma prorenin-renin system. On a regular sodium intake, healthy conscious dogs apparently have a much lower plasma renin activity (PRA) than healthy human volunteers. Cryoactivation of prorenin is virtually absent in dogs, in contrast to that in humans, but becomes more effective after preacidification of the plasma. The concentration of trypsin required for optimal activation of prorenin is 6 to 10 times higher for dog plasma, revealing a prorenin:renin ratio about 10 times greater than in humans. Dialysis of posttryptic plasma decreases the PRA, but it remains 5 times higher than in pretryptic plasma, indicating that activation is not totally dependent on any renin system component that has been rendered dialyzable by trypsin, e.g., substrate converted to tetradecapeptide (TDP). This argues against the view that tryptic activation is attributable to angiotensin production from TDP by the action of cathepsin D, rather than from new renin converted from prorenin. The posttryptic increase in PRA is evident whether plasma incubation is carried out at pH 6.0 or at 7.4, and can be largely blocked by pepstatin, which also implicates a prorenin-renin mechanism rather than TDP-cathepsin. The low PRA in dogs, the negligible cryoactivation and its improvement by preacidification, and the requirement and tolerance of high trypsin concentrations, all point to greater protease inhibition in dog plasma and/or departures from the enzyme(s) responsible for human prorenin activation. Moreover, the tryptic activation of prorenin is not completed quickly as in human plasma, but carries over into the posttryptic stage of angiotensin generation, even in the presence of excess soybean trypsin inhibitor (SBTI), and other potent inhibitors. Such ongoing prorenin activation cannot be attributed only to trypsin itself, nor to kallikrein (both are inhibited by SBTI), but rather to some other enzyme(s) derived by the action of trypsin. This new prorenin convertase activity (possibly renin itself) can be effectively transferred from trypsinized to control dog plasma, in which it greatly accelerates prorenin activation. Thus, contrary to other reports, dog plasma has a high content of activatable prorenin, and with appropriate methodological changes, the dog can be used as an animal model for physiological and biochemical studies of the prorenin-renin system.
Canine neonatally induced coarctation hypertension in the second year. Variably hyperresponsive plasma renin activity.
Authors: Bagby S P , Baur G M
Published: June 2012

In canine neonatally-induced coarctation hypertension, we reported abnormally elevated plasma renin activity (PRA) during sodium restriction in 2-year-old dogs, but found normal PRA responses to sodium restriction +/- furosemide in coarcted dogs studied serially over the first year postaortic banding (PAB). To resolve this apparent discrepancy in PRA response, longitudinal studies were extended to 2 years PAB. In two separately-studied groups, each with three coarcted and three littermate controls, measurements of indirect forelimb blood pressure (BP) at 15 to 18 months, direct brachial arterial BP at 24 months, and serial measurement of PRA and extracellular volume (ECV, as 24Na space) were made over a 15- to 24-month age range during three sodium-volume levels: ad libitum sodium intake (NS), low-sodium diet alone (LS), and low-sodium plus Lasix (LS/Lasix). While PRA in coarcted dogs of both groups was comparable to controls at NS and LS, PRA in Group 1 coarcted dogs significantly exceeded that of littermates during LS/Lasix in both 18- and 24-month studies. In contrast, PRA in Group 2 coarcted dogs was not hyperresponsive to LS/Lasix as compared to simultaneously-studied littermates. The hyperresponsive PRA in Group 1 coarcted dogs could not be attributed to larger absolute or relative ECV deficits. Overall, ECV in coarcted dogs of each group was higher on the average but was not statistically different from controls. Results indicate that the hyperresponsive PRA in this canine model is: 1) a variable feature, developing secondarily in the late established phase; 2) reproducible for a given animal; and 3) not attributed to exaggerated ECV deficits during the LS/Lasix protocol.
Membrane mechanisms in arterial hypertension.
Authors: Harder D R , Hermsmeyer K
Published: June 2012

The purpose of this review is to focus on alterations in vascular muscle membrane potentials (Em), ionic permeabilities, and ionic transport systems which may either contribute to or be a consequence of the hypertensive state. Three models of hypertension are discussed: 1) deoxycorticosterone-salt (DOCA-salt)-induced hypertension; 2) low-renin (presumably volume expanded) renal hypertension (LRRH); and 3) the spontaneously hypertensive rat (SHR) of the Okamoto-Aoki Kyoto-Wistar strain and its normotensive genetic control (WKY). The importance of studying all possible mechanisms of increased contraction in vascular smooth muscle is stressed.
Humoral factor in pressor hyperresponsiveness in renal prehypertensive rabbits.
Authors: Johnson J A , Kurz K D , Siripaisarnpipat S , Koivunen D G , Zeigler D W , Sakamaki T , Payne C G
Published: June 2012

Prehypertensive rabbits with renal artery stenosis of 3 days' duration (one-kidney, one clip) are known to have increased pressor responses to norepinephrine and vasopressin; this pressor hyperresponsiveness is restored to normal by the angiotensin II (AII) antagonist, [ Sar1, Ile8 ] AII, even though plasma renin activity (PRA) and plasma AII concentrations are not elevated. In the present study, the cross-circulation of blood between conscious one-kidney, 3-day renal artery stenosis rabbits and conscious normal rabbits resulted in the transfer of pressor hyperresponsiveness to the normal rabbits, although both groups of rabbits had normal values for PRA. A similar cross-circulation of blood between one-kidney rabbits without renal artery stenosis and normal rabbits did not alter the pressor responsiveness of the normal rabbits to norepinephrine. It was concluded that a circulating humoral factor is involved in mediating pressor hyperresponsiveness in 3-day renal artery stenosis rabbits. To evaluate the interrelationship between AII and the hormonal hyperresponsiveness factor, an additional experiment was performed in which blood was cross-circulated between one-kidney, 3-day renal artery stenosis rabbits and normal rabbits, with the normal rabbits receiving [ Sar1, Ile8 ] AII immediately following cross-circulation. Administration of this AII antagonist to the normal rabbits prevented them from showing pressor hyperresponsiveness following the cross-circulation of blood. It is concluded that in this prehypertensive renal artery stenosis model the humoral hyperresponsiveness factor exerts its effect through AII mechanisms, rather than AII acting to increase the release or secretion of the hyperresponsiveness factor.
The conscious instrumented rabbit: a model for the study of mechanisms of blood pressure regulation during pregnancy.
Authors: Donker A J , Min I , Venuto R C
Published: June 2012

Conscious pregnant and nonpregnant rabbits were used to further evaluate the role of prostaglandin (PG) and plasma renin activity (PRA) in the systemic hemodynamics of pregnancy. Pregnant rabbits had high peripheral blood levels of both PGE2 and PRA. Systemic blood pressure was not affected in either pregnant or nonpregnant by the administration of an inhibitor of prostaglandin synthesis. Pregnant rabbits, however, had a much larger decrease in blood pressure than nonpregnant animals when given the angiotensin I (AI)-converting-enzyme inhibitor, captopril. Pregnant rabbits were more resistant to the pressor effect of exogenous AII than nonpregnant animals. The pressor effect of AII increased in pregnant rabbits after the administration of meclofenamate and parturition but was not changed by volume expansion. In contrast, the sensitivity of nonpregnant rabbits to AII increased after volume expansion, but not after treatment with inhibitors of prostaglandin synthesis. These studies demonstrate that a remarkable similarity exists between pregnant rabbits and pregnant women in the pressor response to AII. This study is the first to correlate the vasopressor response to AII with PRA and the level of a circulating vasopressor prostaglandin in pregnant animals. The results strongly suggest that this model will be fruitful in further attempts to define the factors controlling systemic hemodynamics during pregnancy.
Influence of carboxyhemoglobin, gamma-glutamyl-transferase, body weight, and heart rate on blood pressure in middle-aged men.
Authors: Henningsen N C , Janzon L , Trell E
Published: June 2012

Carboxyhemoglobin (COHb%) and gamma-glutamyl-transferase (GGT) are indicators of tobacco and alcohol consumption; similarly, body weight broadly reflects dietary habits. Relationships between COHb%, GGT, relative body weight, heart rate and blood pressure were studied in 242 48-year-old men attending a general health screening program in Malmö, Sweden. All were without treatment for high blood pressure. Positive correlations were found between blood pressure and body weight, GGT, and pulse, and a reciprocal correlation between blood pressure and COHb%. Use of objective markers for known or suspected risk factors, such as alcohol consumption, smoking, or overweight, were studied to elucidate their usefulness for further prospective studies.
Opiate receptors and cardiovascular control in conscious SHR and WKY rats.
Authors: Feuerstein G , Zerbe R L , Faden A I
Published: June 2012

This study examined the cardiovascular, respiratory, and sympathetic effects of selective mu and delta opioid agonists microinjected into the hypothalamic nucleus preopticus medialis (POM) of conscious SHR and WKY rats. The mu receptor agonist D-Ala2-MePhe4-Gly5-ol-enkephalin (DAGO) at a dose of 0.6 or 6.0 nanomoles (Nmol) increased the blood pressure and heart rate in WKY rats. In SHR rats, the lower dose of DAGO similarly had a pressor effect whereas the higher dose was depressor; heart rat was increased only by the 6.0 nmol dose in these animals. In both SHR and WKY rats, this opioid caused respiratory acidosis and elevation of plasma norepinephrine (NE) and epinephrine (E); plasma vasopressin was reduced by the higher dose of DAGO. All of these effects of the mu agonist were reversed by the opiate receptor antagonist naloxone (0.5 mg/kg, i.a.). The delta opiate-receptor agonist D-Ala2-D-leu5-eukephalin at a dose of 6.0 or 20.0 nmol increased blood pressure and heart rate in both SHR and WKY rats without affecting respiratory variables. Plasma NE and EPI were elevated at the peak of the pressor period. These studies suggest that the anteroventral hypothalamic region may be an important site in central autonomic regulation by opioid peptides. The mu-receptor agonist was more potent than the delta agonist in eliciting cardiovascular and respiratory effects and associated sympatho-adrenomedullary activation.(ABSTRACT TRUNCATED AT 250 WORDS)
Essential hypertension: improved differentiation by the temperature dependence of Li efflux in erythrocytes.
Authors: Levy R , Paran E , Keynan A , Livne A
Published: June 2012

Kinetic and thermodynamic properties of red cell lithium (Li) efflux were examined in patients with essential hypertension; the maximal rate of Li efflux as affected by temperature was measured at the range of 12 degrees to 42 degrees C. Fifty-two patients with essential hypertension and 22 normotensives were studied. The mean Li efflux, both into sodium (Na) medium and Li-Na countertransport, was higher in hypertensive than in normotensive persons, but the distinction between the two groups was limited by extended scatter and overlap. The distinction could be markedly improved by determining the effect of temperature on Li efflux. While all the normotensives exhibited Arrhenius plots of Li efflux with a change in slope ("break") around 30 degrees C, the corresponding "break" for most (75%) of the hypertensives was about 20 degrees C. Consideration of both the rate and the temperature dependence of Li efflux further improved the differentiation of hypertensive patients. Analysis of normotensive offspring of hypertensives and of patients with secondary hypertension indicates that the temperature dependence of Li efflux may serve as a genetic marker for essential hypertension.
Attenuation of the microcirculation in young patients with high-output borderline hypertension.
Authors: Sullivan J M , Prewitt R L , Josephs J A
Published: June 2012

Previous studies have shown abnormalities of the microvasculature in the spontaneously hypertensive rat and human subjects with established hypertension. We have studied the conjunctival microvasculature in relation to systemic and forearm hemodynamics in 24 normal subjects (NL) and 10 subjects with intermittent elevation of blood pressure (BHT). Macrophotographs of the conjunctival circulation were measured for arteriolar diameter and density of arterioles, capillaries, and venules. Blood pressure was measured by Arteriosonde, cardiac index by echocardiography, and forearm hemodynamics by mercury-filled strain-gauge venous occlusion plethysmography. Average diastolic blood pressure in the NL group was 74 +/- 1.7 mm Hg, while that of the BHT subjects was 89 +/- 3.1 mm Hg (p less than 0.005). Capillary density, venous density, and total vascular density were significantly lower in the BHT than NL group, while arteriolar density did not differ significantly. Cardiac index was significantly higher, and peripheral vascular resistance significantly lower, in the BHT as compared to the NL subjects. Forearm blood flow was higher in the NL subjects. The diameter of the preterminal arterioles of the BHT subjects was 27% greater than NL (p less than 0.02). The capillary density was inversely related to the cardiac index (r = -0.482, p less than 0.01), but was not related to blood pressure (r = -0.207). We conclude that the high cardiac output phase of early essential hypertension in humans is accompanied by a reduction in the number of filtering capillaries, and that the rarefaction of capillaries is more closely related to the elevation of cardiac output than to raised blood pressure.
Time course of development of the antihypertensive effect of propranolol.
Authors: Fagan T C , Walle T , Corns-Hurwitz R , Conradi E C , Privitera P , Harmon G , Degenhart W , Gaffney T E
Published: June 2012

Ten patients with essential hypertension were hospitalized and treated with placebo, followed by their usual dose of propranolol. Systolic and diastolic blood pressure decreased significantly after the first dose of propranolol, and by the third day of propranolol treatment reached 84% to 92% of the maximum decrease achieved during the 6 days of treatment. Mean maximum falls in blood pressure were 13/12 mm Hg supine and 12/13 mm Hg standing. This development of the decrease in heart rate and blood pressure over 48 hours occurred in parallel with cumulation of propranolol to steady state in plasma. The decrease in diastolic, but not systolic, arterial pressure was directly related to pretreatment blood pressure, but not significantly related to pretreatment plasma renin activity (PRA) or change in PRA. Thus, single doses of propranolol lowered blood pressure in patients with essential hypertension, and with continued therapy, near maximum antihypertensive effects were achieved within 48 hours.
Evaluation of plasma catecholamines in humans. Correlation of resting levels with cardiac responses to beta-blocking and sympatholytic drugs.
Authors: Thomas J , Fouad F M , Tarazi R C , Bravo E L
Published: June 2012

The changes in systolic time intervals (STI) following reduction of adrenergic activity was used to validate supine resting plasma catecholamines (CATs) as an index of sympathetic activity. Blockade of sympathetic activity was achieved by two means in two groups: propranolol (10 mg i.v.) and clonidine (0.3 mg p.o.). The diminished sympathetic effect was evidenced by slowing (p less than 0.01) of heart rate with both drugs and the reduction (p less than 0.01) of blood pressure with clonidine. There was no correlation in our study between resting plasma CATs (norepinephrine alone or total), and changes in heart rate and preejection period (PEP). Moreover, to avoid changes in PEP that could be related to differences in blood pressure levels (clonidine-reduced blood pressure while propranolol did not), the changes in PEP were corrected for the change of mean arterial pressure (MAP) in the same patients (delta PEP/(delta MAP and % delta PEP/% delta MAP). No correlation could be found, still, between resting supine plasma CATs and these ratios. The difficulty in demonstrating a correlation between resting plasma CATs and the immediate cardiac response to adrenolytic agents can be explained by the number of factors influencing plasma levels. Circulating plasma CATs represent the spillover from adrenergic nerve endings, and, therefore, their level would depend on several factors including sympathetic nervous system activity, rate of reuptake, and rate of degradation.
Studies of hypertension-induced vascular hypertrophy in cultured smooth muscle cells from spontaneously hypertensive rats.
Authors: Kanbe T , Nara Y , Tagami M , Yamori Y
Published: June 2012

Mechanisms of vascular hypertrophy induced by hypertension were studied in cultured aortic smooth muscle cells from spontaneously hypertensive rats (SHR) and stroke-prone SHR (SHRSP) and compared with those from normotensive Wistar-Kyoto (WKY) rats. Fetal calf serum-stimulated ornithine decarboxylase (ODC) activity of cultured smooth muscle cells was greater in SHR and SHRSP than in WKY. Beta- but not alpha-adrenergic agonist stimulated ODC activity acutely in cultured smooth muscle cells from WKY, and isoprenaline-induced activation was blocked by the beta-blocker, propranolol, and enhanced by the phosphodiesterase inhibitor, 1-methyl-3-isobutylxanthine. These results indicate that cultured vascular smooth muscle cells from SHR and SHRSP are more prone to increase the protein synthesis than those from WKY through the trophic induction of ODC activity and that the regulation of ODC activity by catecholamines is mediated through beta-agonistic effect in cultured smooth muscle cells.
Baroreflex control of myocardial contractility in conscious normotensive and renal hypertensive rabbits.
Authors: Aylward P E , McRitchie R J , Chalmers J P , West M J
Published: June 2012

We have assessed resting myocardial contractility and its baroreflex control in normotensive and hypertensive conscious rabbits. Hypertension was induced by bilateral cellophane wrapping of the kidneys with experiments performed 6 weeks later during the established phase of hypertension. The peak rate of change of left ventricular pressure (peak LV dP/dt) was used as the index of myocardial contractility. Baroreflex control of contractility and heart period (HP) was assessed by constructing stimulus response curves relating change in mean arterial pressure (MAP), induced by balloon occluders around the abdominal aorta and inferior vena cava, to change in peak LV dP/dt and HP. These stimulus response curves were obtained in normotensive rabbits with and without cardiac pacing, and in both normotensive and hypertensive animals after cardiac beta sympathetic blockade with propranolol, vagal blockade with methylscopolamine, and combined cardiac autonomic blockade with propranolol and scopolamine, as well as in rabbits with intact autonomic effectors. Resting MAP was significantly higher in the hypertensive rabbits (119 +/- 2 mm Hg) compared to normotensive controls (76 +/- 1 mm Hg). Resting peak LV dP/dt was also greater by 51% in the hypertensive animals (7054 +/- 287 mm Hg sec-1) compared to controls (4690 +/- 223 mm Hg sec-1). There was no significant difference in the resting heart period or resting left ventricular end diastolic pressure. Transient changes in MAP induced by occlusion of the aortic or venous balloons produced significant alterations in peak LV dP/dt in normotensive animals with and without pacing and in hypertensive control animals. In animals with cardiac sympathetic block, the range and slope or sensitivity of the stimulus response curves were not significantly changed but in animals with vagal blockade the sensitivity was reduced by 90% and the range at 30 mm Hg by 88%. After propranolol and methylscopolamine were administered together, the stimulus no longer evoked a response. These experiments demonstrate that myocardial contractility is under baroreflex control and suggest that this is mediated principally via parasympathetic nerves to the heart. There was no significant difference between the sensitivity of baroreflex control of myocardial contractility in the normotensive (-84 +/- 14 mm Hg sec-1 per mm Hg) and the hypertensive (-110 +/- 14 mm Hg sec-1 per mm Hg) rabbits, unlike the baroreflex control of heart period where sensitivity was markedly impaired in the hypertensive (sensitivity 3.8 +/- 0.8 msec/mm Hg) compared to the normotensive (6.9 +/- 1.0 msec/mm Hg) animals.
Effects of vasodilation on plasma distribution in SHR cremaster muscle microvessels.
Authors: Baker C H , Wilmoth F R , Sutton E T
Published: June 2012

Alterations in the structure, number, reactivity, contractility and sensitivity of resistance vessels of hypertensive animals have been reported. If the etiology of hypertension is due to one or a combination of these factors, it could logically be expected that the distribution of blood flow from the arterial to venous circulation through parallel microcirculatory circuits could be affected. The right cremaster muscles of pentabarbital anesthetized Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) (6-8 weeks old) were exposed and prepared for fluorescent videomicroscopy. The right iliac artery was cannulated with PE-10 tubing, the tip of which was placed at the aortic bifurcation for bolus injections of FITC-dextran (70,000 molecular weight) and arterial pressure measurement. Passage of the indicator through the microcirculation was recorded on videotape during control and during vasodilation by topical application of adenosine (0.2 M). Time-concentration curves were recorded by means of dual window videodensitometry upon replay of the tape. Arterial pressure averaged 85 +/ 3 mm Hg in WKY rats and 110 +/- 5 mm Hg in SHR. Arteriolar flow velocity varied directly with small arteriolar diameter. Dilation significantly reduced the venular appearance (ta), mean transit time (t), and curve width time (tE) in WKY and SHR. The ta was significantly more reduced in SHR than WKY. This would suggest that, in WKY, dilation may have opened some new parallel circuits but principally increased flow velocity through existing circuits. In SHR, new shorter and/or higher velocity circuits were opened as evidenced by the reduced ta with the longer and/or lower velocity circuits largely unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)
Human chromogranin A. Purification and characterization from catecholamine storage vesicles of human pheochromocytoma.
Authors: O'Connor D T , Frigon R P , Sokoloff R L
Published: June 2012

Chromogranin A is the quantitatively major soluble protein in catecholamine storage vesicles of the adrenal medulla and sympathetic nerve, and has been a useful index of exocytosis during sympathoadrenal neurosecretion. To probe human catecholamine storage and release, we isolated chromogranin A from chromaffin tissue in human pheochromocytoma, and compared it to chromogranin A isolated from chromaffin tissue in bovine adrenal medulla. The preparation included catecholamine storage vesicle isolation by sucrose gradient centrifugation, removal of dopamine-beta-hydroxylase by affinity chromatography on Concanavalin A-Sepharose, and preparative polyacrylamide gel electrophoresis. Human and bovine chromogranin A displayed considerable interspecies homology. Human chromogranin A is a 68,000 dalton monomeric protein with an unusual amino acid composition (31.53 weight % glutamic acid); an acidic, microheterogeneous isoelectric point (4.57-4.68); a characteristic tryptic digest peptide map; and marked dissimilarity to dopamine-beta-hydroxylase in all properties studied. A new probe of human sympathoadrenal function is available in chromogranin A.
Role of the renin-angiotensin system in the control of vasopressin and ACTH secretion during the development of renal hypertension in dogs.
Authors: Ben L K , Maselli J , Keil L C , Reid I A
Published: June 2012

Experiments were performed to determine if the activation of the renin-angiotensin system that occurs during the development of two-kidney, one clip Goldblatt hypertension in dogs is accompanied by increases in vasopressin and adrenocorticotrophic hormone (ACTH) secretion. Following renal artery constriction, there were marked increases in arterial blood pressure, plasma renin activity (PRA), and plasma angiotensin II (AII) concentration. These changes were accompanied by an increase in plasma vasopressin concentration during the second week following constriction, and there were significant correlations between plasma vasopressin concentration and PRA (r = 0.57, p less than 0.001), and between plasma vasopressin concentration and plasma AII concentration (r = 0.59, p less than 0.001). In contrast, plasma corticosteroid concentration, used as an index of changes in ACTH secretion, did not change significantly. Acute blockade of the renin-angiotensin system with captopril or saralasin produced the expected changes in blood pressure, PRA, and plasma AII concentration but did not decrease plasma vasopressin or corticosteroid concentrations. These results indicate that during the development of renal hypertension in dogs, there may be an interaction between the renin-angiotensin system and vasopressin, but not between the renin-angiotensin system and the pituitary-adrenal axis. They also show that the antihypertensive action of captopril in this experimental model is not mediated via suppression of vasopressin, ACTH, or corticosteroid secretion.
Urinary kallikrein response to acute saline or water loads in hypertensive and normal humans.
Authors: Lawton W J
Published: June 2012

Urinary kallikrein excretion during acute water or saline loading was studied in normal and hypertensive humans after chronic Na+ depletion and Na+ loading to answer the following questions. 1. Is urinary kallikrein a natriuretic or diuretic substance? 2. During acute water or saline loading, does the underlying Na+ balance influence (a) the urinary kallikrein response? or (b) the relationship between urinary kallikrein and renal Na+ or water handling? 1) Urinary kallikrein did not change during a 1.2 liter water load given to nine white hypertensive and five white normal men. Urinary kallikrein was significantly decreased, however, in five white hypertensive and five white normal subjects during and after 1 hour of isotonic saline infusion (30 ml/kg). In sodium-depleted hypertensive patients kallikrein excretion was decreased from 19.8 to 9.5 mEU /min, and in Na+-depleted normal subjects it was decreased from 15.7 to 12.6 mEU /min (p = 0.003). The response in hypertensive patients was not different from normal subjects. In all Na+-loaded subjects, kallikrein excretion was also significantly decreased during isotonic saline infusion (p = 0.01). Urinary kallikrein did not change in three other subjects given hypertonic saline. 2(a) The underlying state of Na+ balance influenced the baseline level of kallikrein excretion, but not the directional decline in kallikrein during isotonic saline. (b) In Na+-restricted hypertensives given isotonic saline, urinary kallikrein was inversely related to the fractional excretion of Na+ (r = -0.54, p less than 0.01) and the tubular reabsorption of H2O (TcH2O/GFR; r = -0.50, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Lack of an effect of dietary saturated fat and cholesterol on blood pressure in normotensives.
Authors: Sacks F M , Marais G E , Handysides G , Salazar J , Miller L , Foster J M , Rosner B , Kass E H
Published: June 2012

The effect on blood pressure (BP) levels of modifying the saturated fat and cholesterol content in the diet was studied in two separate protocols in normotensive volunteers. For 3 months, 19 men and women, aged 14 to 54 years, adhered to a diet that eliminated meat, poultry, eggs, and dairy fat from the subjects' customary nonvegetarian diet, which had included 71 g/day (35%) of dietary fat. The experimental diet reduced the consumption of saturated fat from 21 to 10 g, dietary cholesterol was lowered from 398 to 69 mg per day, but consumption of polyunsaturated fatty acids, carbohydrates, and dietary fiber was unchanged. Body weight and urinary sodium and potassium excretion were not significantly altered. Mean BP before and after the low fat diet was 116/74 and 115/74 mm Hg, respectively. A second double-blind study tested the effect on BP of dietary cholesterol at levels of 155 and 471 mg/day. Seventeen semivegetarian college students consumed one egg per day concealed in desserts for 3 weeks, and identical desserts containing no eggs for an additional 3 weeks. Mean BP at the end of the egg and eggless periods was 108/69 and 107/69 mm Hg, respectively. Thus, in short-term nutritional studies, dietary saturated fat and cholesterol at low-to-moderate levels of intake have no significant effects on BP in normotensive adults.
Effect of antihypertensive treatment on the behavioral consequences of elevated blood pressure.
Authors: Miller R E , Shapiro A P , King H E , Ginchereau E H , Hosutt J A
Published: June 2012

It was shown in a prior study that mildly hypertensive patients performed significantly less effectively on several sensory-perceptual, cognitive, and psychomotor tests than did matched normotensive controls. To determine whether these deficits are attributable to elevated blood pressure per se, hypertensive and control subjects were recalled for reexamination 15 months after the original tests. Results indicated that those hypertensives in whom blood pressure had been lowered with antihypertensive drugs showed significant restoration of performance scores toward the levels of normotensive subjects. Hypertensives who had not received active treatment remained deficient as compared with controls. These results indicated that behavioral deficits in mild hypertension may be reversible consequences of the effects of elevated blood pressure on the central nervous system.
Evaluation of the Remler M2000 blood pressure recorder. Comparison with intraarterial blood pressure recordings both at hospital and at home.
Authors: Gould B A , Hornung R S , Kieso H A , Altman D G , Cashman P M , Raftery E B
Published: June 2012

The Remler M2000 is a semiautomated device that has been used to collect epidemiological data and assess blood pressure variability. It has been subjected to limited evaluation in operation, however, and no studies of its accuracy away from the hospital or office environment have been undertaken. We recruited a group of 28 patients with essential hypertension who were undergoing intraarterial ambulatory blood pressure monitoring and compared the intraarterial recordings with those made with the Remler instrument both at home and in the hospital. The Remler recordings were also compared with simultaneous indirect blood pressure measurements made with the random zero sphygmomanometer. The mean difference between the Remler and intraarterial blood pressure recordings was -3/7 in the hospital and 7/0 at home. All standard deviations were greater than 10 mm Hg, indicating large between-subject variability. Overall, the relationship of the Remler M2000 readings to intraarterial pressures was as close if not closer than standard indirect sphygmomanometry and thus might provide useful data for epidemiological surveys or drug trials. It would appear that for accurate measurement of short-term blood pressure variation and 24-hour recording, intraarterial recording is the method of choice.
Kininogenase activity of tonin.
Authors: Ikeda M , Arakawa K
Published: June 2012

Tonin, known for its specific and direct generation of angiotensin II, was highly purified from rat submaxillary gland and investigated for kininogenase activity. For the substrate, heat-treated plasma from ox blood, and highly purified low-molecular-weight (LMW) and high-molecular-weight (HMW) kininogens, were used. The reaction product formed at pH 8.0 well satisfied the characteristics of kinin, i.e., depressor and oxytocic activities and reactivity with antibradykinin antiserum. Kinin formed by tonin from purified LMW kininogen was identified with bradykinin in high performance liquid chromatography and radioimmunoassay. The results revealed tonin's new capability of forming kinin in addition to the hitherto known pressor angiotensin II, indicating tonin, too, is a member of the "kinin- tensin enzyme system."
Immunoreactive renin in mouse adrenal gland. Localization in the inner cortical region.
Authors: Naruse M , Naruse K , Inagaki T , Inagami T
Published: June 2012

The existence of renin in the adrenal gland of the mouse was determined by its enzymatic activity and by immunohistochemical techniques using monospecific antibodies to mouse submandibular gland renin. The adrenal gland of mouse was found to contain a very high level of renin significantly greater than other mouse tissues except for the kidney and submandibular gland. Also, the renin level in mouse adrenal was significantly higher than that in adrenals of other species. This renin activity was distinct from the nonspecific renin-like activity of acid proteases in that its activity was optimal at neutral pH and specifically inhibited by antirenin antibody. Adrenal renin increased upon nephrectomy indicating that it is not derived from the kidney. Immunohistochemical studies localized the renin-immunoreactive substance to cells in the inner region of the cortex. The intensity of staining was highest in the innermost region and decreased in cells in outer layers.
Diastolic function of the heart in untreated primary hypertension.
Authors: Hartford M , Wikstrand J , Wallentin I , Ljungman S , Wilhelmsen L , Berglund G
Published: June 2012

To study left ventricular (LV) diastolic function of the heart in relation to blood pressure (BP) and other signs of hypertensive cardiac and peripheral vascular changes, isovolumic relaxation time and early diastolic filling were determined in four BP groups of untreated 49-year-old men: normotensive subjects (n = 20), men with borderline hypertension (n = 30), mild hypertension (n = 45), and moderate to severe hypertension (n = 24). Isovolumic relaxation time, measured as the distance between aortic closure (A2, phonocardiography) and mitral valve opening (echocardiography), and early diastolic filling, measured as the distance between mitral valve opening and the O point of the apexcardiogram, tended to increase with BP level, and the total interval from aortic closure to the O point (A2O interval) was significantly prolonged in the two groups with mild and moderate to severe hypertension. A prolonged A2O interval (greater than or equal to 117% of expected value at observed heart rate) was seen in several hypertensives, who had no obvious increase in LV wall thickness on M mode echocardiography. This suggests that a prolonged LV relaxation time may be an early sign of cardiac involvement in primary hypertension. In the group with moderate to severe hypertension, an increase in LV wall thickness was seen together with an increase in resistance at maximal dilation in the calf. This supports the theory that when changes in cardiac structure develop they occur in parallel with structural changes also in the periphery.
Red cell sodium countertransport and cotransport in normotensive and hypertensive blacks.
Authors: Canessa M , Spalvins A , Adragna N , Falkner B
Published: June 2012

We have previously described elevated Lii -Nao countertransport (CT) and Na-K cotransport (CO) in red cells of Caucasian patients from Boston. In this study, we report both transport systems in black patients from Philadelphia. The maximal rate (Vmax) of CT was assayed by measuring the Nao-stimulated Li efflux from cells containing +/- 6 mmol Li/liter. The Vmax of outward cotransport was assayed by measuring the furosemide-sensitive component of Na and K efflux into Mg medium from cells containing 50 mmol/liter of both ions. The mean value of CT for 18 normotensive (NT) subjects with no family history of hypertension, (-) FHH , was 0.18 +/- 0.05 (mmol/liter cells X hour); and in 14 hypertensive (HT) patients, 0.18 +/- 0.07. The mean values of Na and K cotransport were, respectively (mmol/liter cells X hour), in 18 NT subjects with (-) FHH , 0.38 +/- 0.24 and 0.50 +/- 0.28 in 18 HT subjects, 0.25 +/- 0.17 and 0.24 +/- 0.14. We conclude that there is no difference in the Vmax for CT between the two groups of black subjects, but that the Vmax for Na-K CO was significantly reduced in the HT group. Notably, the offspring of HT patients (age 14 years, n = 17) also had a marked reduction in the Vmax of Na (0.15 +/- 0.17) K cotransport (0.19 +/- 14) in comparison with the mean value of Na (0.40 +/- 0.2) and K (0.60 +/- 0.3) cotransport measured in offspring (n = 10) of NT subjects (age 14 years).(ABSTRACT TRUNCATED AT 250 WORDS)
Purification of hog kidney renin with immobilized monoclonal antirenin.
Authors: Dorer F E , Levine M , Skeggs L T , Lentz K E , Kahn J R
Published: June 2012

Spleen cells from mice immunized with partially purified hog kidney renin were fused with mouse myeloma cells to produce a stable monoclonal hybridoma cell line that synthesizes an antibody against renin. A single monoclonal antibody was chosen for study and has been produced in large quantity and purified by affinity chromatography on protein A-Sepharose. The antirenin, which belongs to the IgG1 subclass, exhibits anticatalytic activity against both hog and rabbit renin. An immunoaffinity column prepared from antibody coupled to Sepharose has been used in the purification of renin from hog kidney. Although renin is quantitatively adsorbed from solution, it can be eluted from the column under gentle conditions. The highly purified renin, with specific activity of 2122 Goldblatt Units/mg protein, exhibits both charge (pH 4.1 to 5.1) and size (38,000 to 42,700) heterogeneity. Hog kidney renin dissociates in the presence of sodium dodecyl sulfate (SDS) and mercaptoethanol to heavy and light chains with molecular weights of 33,700 and 5,800, respectively. In the presence of SDS, a small amount of a nw form of renin is observed with a molecular weight of 19,500 which retains activity on renaturation. The monoclonal antibody should be a useful tool for the study of the renin-angiotensin system and especially for the purification of renin. The hybridoma cell line used in this study (F-32 VIII C4) has been donated to the American Type Culture Collection.
Investigations of components of the renin-angiotensin system in rat vascular tissue.
Authors: Rosenthal J H , Pfeifle B , Michailov M L , Pschorr J , Jacob I C , Dahlheim H
Published: June 2012

Investigations were performed on components of the renin-angiotensin system (RAS) in homogenate extracts of vascular tissue and aortic smooth muscle cells cultivated in vitro. Determinations of isoelectric points and pH optima indicated the existence in aortic homogenate extracts of two local angiotensin I (AI)-forming enzymes (AIFE) that were different from those of plasma, renal cortex, veins, and aortic smooth muscle cells. The pH optima for AI-converting enzyme (ACE) from vascular tissues, aortic smooth muscle cells, and plasma were in the same range (pH 8.0-8.5), and in agreement with those measured previously in other tissues. In contrast, in vitro studies with the ACE inhibitors MK-421 and MK-422 and measurement of isoelectric points suggested that aortic ACE was different from the plasma enzyme. AIFE and ACE activities were found to be elevated in spontaneously hypertensive rats (SHR). The biochemical characteristics of the enzymes investigated in the vascular tissue of SHR were not different from those of the normotensive controls. AI- and AII-degrading enzymes were found both in aortic tissue and in aortic smooth muscle cells. One potent AI-degrading enzyme different from ACE was observed in aortic tissue. A high ratio of AI/AII immunoreactivities in arterial walls suggests the availability of renin substrate, and that AI-degrading enzymes are the rate-limiting enzymes for AII formation. The results further support the concept of an intrinsic vascular RAS.
Cardiovascular and renal action of platelet-activating factor in anesthetized dogs.
Authors: Vemulapalli S , Chiu P J , Barnett A
Published: June 2012

Platelet-activating factor (PAF) has hypotensive effects similar to those of antihypertensive polar renomedullary lipid (APRL), a potent endogenous hypotensive lipid. In this study the cardiovascular and renal effects of PAF were characterized in anesthetized dogs. Intravenous infusion of PAF at 0.1 micrograms/kg/min for 1 hour caused marked reduction in arterial blood pressure and cardiac output and was accompanied by minimal changes in heart rate. Concomitantly, renal blood flow, glomerular filtration rate, urine flow, and fractional excretion of Na+ and K+ fell significantly. Plasma renin activity was greatly stimulated (11.9 +/- 1.66 vs 3.26 +/- 0.45 ng/angiotensin I/ml/hr for the placebo group). There were no significant alterations in any of these parameters following PAF at a lower dose (0.03 micrograms/kg/min for 1 hour). In a separate study, PAF at 0.1 micrograms/kg/min for 20 minutes produced a decrease in left ventricular myocardial contractile force, concomitant with bradycardia and hypotension, which indicated the presence of a negative inotropic activity. It is concluded that systemic administration of PAF has a deleterious effect on kidney function due to arterial hypotension and diminished cardiac output.
Severe hypertension in childhood due to prolonged skin application of a mineralocorticoid ointment.
Authors: Bartorelli A , Rimondini A
Published: June 2012

We report the case of a 9-year-old boy suffering from exzematous dermatitis who was treated for 6 years with a daily dose of 100 mg of a dermatological ointment containing 9 alpha-fluoroprednisolone-21-acetate. At examination the patient's blood pressure was persistently 230/160 mm Hg and was considered essential in origin after secondary forms of arterial hypertension had been excluded. Treatment with nifedipine and labetalol lowered the blood pressure to 150/100 mm Hg. When we became aware of the dermatological treatment, we advised its discontinuance. In the subsequent 7 days, the blood pressure fell to hypotensive levels (75/40 mm Hg) and then became normal a few days after discontinuance of the antihypertensive therapy. This case suggests that prolonged use of topical steroids, commonly prescribed for skin diseases, may cause hypertension, especially in childhood.
Evidence for an extrarenal source of inactive renin in rats.
Authors: Doi Y , Franco-Saenz R , Mulrow P J
Published: June 2012

We studied the source of inactive renin in plasma by investigating the changes of active and inactive renin after bilateral nephrectomy in the rat. Active renin rapidly decreased after bilateral nephrectomy, with a half-life of approximately 15 minutes. Inactive renin, on the other hand, was 20.96 +/- 1.63 ng/ml/hr before nephrectomy and gradually increased to reach a peak at 20 hours after nephrectomy (193 +/- 62 ng/ml/hr). The molecular weight of active renin was approximately 40,000 and that of inactive renin was approximately 60,000 on a Sephacryl S-200 column. Inactive renin was separated from active renin by a Cibacron blue column, and the 0 time inactive renin eluted in the same fractions as the inactive renin from 20 hours after nephrectomy. The pH optimum of inactive renin in rat renin substrate was between 5.5 and 7.5, which differs from the optimal value of pepsin or cathepsin D. The increase of inactive renin in nephrectomized rats was not prevented by removal of the salivary glands, uterus, spleen, pancreas, stomach, intestines, adrenal glands, or pituitary. In summary, inactive renin is present in the anephric rat and does not appear to be converted to active renin in the peripheral blood. The source and control of this extrarenal inactive renin are still unclear, but this renin is secreted in the rat within hours after nephrectomy.
Increased susceptibility to osmotic disruption of the blood-brain barrier in chronic hypertension.
Authors: Tamaki K , Sadoshima S , Heistad D D
Published: June 2012

We examined the effects of chronic hypertension and acute reduction of arterial pressure on the susceptibility of the blood-brain barrier (BBB) to disruption. The BBB was disrupted with an intracarotid injection of 1.6 M arabinose in spontaneously hypertensive rats (SHR), stroke-prone SHR (SHRSP), and normotensive Wistar-Kyoto (WKY) rats. Permeability of the BBB was determined from the ratio of 125I-albumin in brain to 125I-albumin in blood. When the BBB was intact, permeability was less than 0.4%. After hypertonic arabinose, permeability of the BBB was greater (mean +/- SE) in SHRSP (17.6% +/- 1.6%) and in SHR (21.1% +/- 3.1%) than in WKY (10.3% +/- 2.4%) (p less than 0.05). When arterial pressure of SHRSP was reduced acutely with nitroprusside before arabinose, the BBB permeability to albumin was not reduced (21.5% +/- 1.5%). In other rats, we examined survival after osmotic disruption. In SHRSP, 14 of 15 rats died within 1 day after osmotic disruption with marked cerebral edema. In WKY, four of 15 rats died (p less than 0.05 vs SHRSP). When arterial pressure of SHRSP was reduced before arabinose, mortality was reduced to six of 15 (p less than 0.05 vs untreated SHRSP). We conclude that the BBB in SHRSP has enhanced vulnerability that is detrimental to survival. Reduction of arterial pressure improves survival in SHRSP without affecting BBB permeability to albumin.(ABSTRACT TRUNCATED AT 250 WORDS)
Role of cardiopulmonary mechanoreceptors in ADH release in normal humans.
Authors: Egan B , Grekin R , Ibsen H , Osterziel K , Julius S
Published: June 2012

Although animal studies have shown that cardiopulmonary receptors regulate the release of antidiuretic hormone (ADH), human studies have produced conflicting results. Consequently, we studied 17 normal healthy men to determine the ADH response to selective unloading (decreased stretch) of cardiopulmonary low-pressure receptors by thigh cuff inflation in the supine position. Thigh cuff inflation of 30 to 40 mm Hg decreased the central blood volume and right atrial pressure (cardiopulmonary receptor load), while mean arterial pressure and pulse pressure were unchanged (arterial baroreceptor load). Thigh cuff inflation to this level did not alter plasma osmolality or cardiac output. Plasma ADH increased an average of 67% (p less than 0.01) following thigh cuff inflation compared to the preceding supine baseline. After thigh cuff deflation (n = 6), the ADH decreased toward preinflation values. We conclude that selective unloading of the cardiopulmonary receptors in humans increases plasma ADH levels.