bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of forebrain periventricular lesions on the development of renal hypertension in rabbits.
Authors: Fink G D , Bryan W J
Published: June 2012

Ablation of tissue surrounding the anteroventral third cerebral ventricle (AV3V) has been demonstrated to prevent and reverse renal hypertension in the rat. The contribution of this brain area to the maintenance of hypertension in other species has not been examined. In the present investigation, an attempt was made to produce two-kidney, one clip renal hypertension in rabbits with histologically and functionally defined AV3V destruction. Electrolytic lesion of the AV3V in rabbits produced effects closely resembling those previously seen in rats: increased plasma volume and plasma sodium, temporary adipsia, no change in resting arterial pressure or heart rate, and significant attenuation of pressor responsiveness to angiotensin II (AII) delivered intracranially. However, the increase in arterial pressure observed over a 4-week period following the application of a 0.5 mm silver clip to the left renal artery (opposite kidney intact) was identical in 12 AV3V-lesioned and 12 sham-operated rabbits. Hypertension development was not accompanied by significant sodium retention, water retention, or plasma/extracellular fluid volume expansion in either group of rabbits. Pressor responses to intravenous infusions of AII and norepinephrine were identical in sham and AV3V-X rabbits. Thus, destruction of the AV3V, and the attendant reduction in the central pressor action of AII, does not alter the pattern of development of two-kidney, one clip renal hypertension in the rabbit. The contrasting results in rats and rabbits could be explained by the differing contribution of the area postrema to the pressor action of AII in the two species.
Diazoxide concentration-response relation in hypertension.
Authors: Ogilvie R I , Nadeau J H , Sitar D S
Published: June 2012

The pharmacokinetic disposition and antihypertensive response of bolus infusions of diazoxide, 1, 2, or 4 mg/kg over 5, 10, or 20 seconds, were examined in seven patients with chronic stable essential hypertension and mean arterial pressures (MAP) between 122 and 155 mm Hg off therapy. Maximal reductions in MAP were noted 2 minutes after each dose, and a linear correlation was obtained in all patients between dose or plasma diazoxide concentration and maximal change in MAP. Individual concentration-time curves were analyzed to determine the apparent volume of distribution at steady state (Vdss range, 0.178 to 0.250 liter/kg), beta t 1/2 (range, 32 to 62.5 hours), and plasma clearance rate (Clp range, 2.2 to 5.3 ml/kg . hour-1) for the calculation of loading and maintenance doses designed to produce steady-state concentrations within 0.5 hours. These infusions resulted in steady-state reductions in MAP (16% to 30%) which could be predicted from the concentration-response curves of each patient after bolus infusions. With the use of kinetic principles, a diazoxide dose regimen (average load, 7.5 mg/kg at 7.5 mg/min; average maintenance, 10% of loading dose every 6 hours) produced gradual and predictable reductions in MAP in patients with accelerated hypertension, since the response was proportional to plasma diazoxide concentrations.
Anomalous response of urinary kallikrein to deoxycorticosterone in Dahl salt-sensitive rats.
Authors: Rapp J P , McPartland R P , Sustarsic D L
Published: June 2012

Previous evidence shows that salt-sensitive (S) rats have a net increase in plasma mineralocorticoid activity due to 18-hydroxy-11-deoxycorticosterone and decreased urinary kallikrein excretion compared to salt-resistant (R) rats. Since mineralocorticoids stimulate urinary kallikrein excretion, these results are inconsistent. This inconsistency was explained by the fact that, while R rats responded normally to treatment with deoxycorticosterone (DOC) by an increase in urinary kallikrein excretion, S rats showed no change in urinary kallikrein even when treated with 10 mg of DOC/day for 24 days. S and R rats responded identically to DOC with changes muscle electrolytes and relative hypertrophy of the renal distal tubule. Other measures of chronic mineralocorticoid response in S rats beside kallikrein were, therefore, intact. It was found that S rats were capable of responding to Na deficient diet with an increase in urinary kallikrein comparable to R rats. It was argued, therefore, that mineralocorticoid receptor mechanisms and distal-tubular cell responsiveness are intact in S rats. Mild glomerular and tubular scarring was found in S rats and the severity of renal lesions was increased by DOC treatment in S rats. These lesions correlated well with blood pressure and proteinuria. No such lesions were present in control or DOC treated R rats. It was suggested that failure of urinary kallikrein to respond to DOC in S rats may be a secondary phenomenon resulting from renal damage.
Time course of arterial wall changes with DOCA plus salt hypertension in the rat.
Authors: Cox R H
Published: June 2012

Segments of carotid and tail artery, and thoracic aorta from control and hypertensive animals (DOCA + salt) were used for the study of mechanics and/or chemical composition. Pressure-diameter measurements were made on intact segments under conditions of active (145 mM-K+) and passive (O-Ca++ and 2 mM-EGTA) smooth muscle. Segments were used for chemical analyses of connective tissue content, water spaces, and electrolyte content. The passive stiffness of carotid and tail arteries increased monotonically with time. The carotids showed significant changes after two weeks of hypertension while the tail arteries only after 12 weeks. The collagen and total connective tissue content of the hypertensive arteries was decreased while collagen/elastin was unchanged. Smooth muscle activation produced larger changes in diameter of hypertensive arteries especially at higher values of transmural pressure. Maximum active force development was increased in carotid arteries at each time period from +2 weeks on while it was increased for the tail arteries only at +2 and +4 weeks. Relative cellular volume of these arteries was monotonically increased with hypertension. Maximum active force normalized to cellular content was not significantly different for carotid arteries from control and DOCA rats. For hypertensive tail arteries normalized on this basis force development remained elevated at +4 weeks but was significantly reduced at +12 weeks. Not all of the response to smooth muscle activation are monotonic with duration of hypertension, nor can all of these changes be explained on the basis of changes in cellular volume.
Augmentation of cardiopulmonary baroreflex control of forearm vascular resistance in borderline hypertension.
Authors: Mark A L , Kerber R E
Published: June 2012

Arterial baroreflex control of heart rate is impaired in young men with borderline or mild hypertension. Despite this impairment, these subjects often have exaggerated increases in vascular resistance during orthostatic stress. We considered the possibility that this exaggerated reflex vasoconstriction might reflect augmented cardiopulmonary baroreflex control of vascular resistance in borderline hypertension (BHT). Accordingly, we studied cardiopulmonary baroreflex control of forearm vascular resistance in nine BHT men with blood pressure intermittently above 150/90 mm Hg and in seven normotensive (NT) men. Cardiopulmonary baroreceptor input was reduced with lower body negative pressure (LBNP-5 to-20 mm HG), which decreases cardiac filling pressures. Baseline mean arterial pressure was 99 /+- 3 mm Hg (mean /+- SE) in BHT vs 83 /+- 2 mm Hg in NT (p less than 0.05). Baseline forearm resistance was also higher in BHT than in NT: 19 /+- 2 vs 13 /+-1 mm Hg/ml/min/100 ml or units (p less than 0.05). Reflex increases in forearm resistance during LBNP were greater (p less than 0.05) in BHT than in NT 8.6 /+- 1.7 vs 4.5 /+- 1.1 units during LBNP-20). Increases in arterial pressure and forearm resistance during a cold pressor test were not significantly different in the two groups. Thus, the augmented response to LBNP could not be attributed to a nonspecific influence of increased baseline resistance or a generalized abnormality in reflex control. In summary, the results of this study suggest that there is augmentation of the tonic inhibitory influence of cardiopulmonary baroreceptors in humans with BHT.
Glomerular hemodynamics in moderate Goldblatt hypertension in the rat.
Authors: Steiner R W , Tucker B J , Gushwa L C , Gifford J , Wilson C B , Blantz R C
Published: June 2012

Glomerular hemodynamics were studied by micropuncture technique in the unclipped kidney in rats in which modest two kidney Goldblatt hypertension was maintained for 4 weeks and in normotensive controls. Both groups ingested less than 2 mEq Na+/day. In hypertensive rats at micropuncture, mean hydrostatic pressure was elevated both systematically (128 +/- 5 vs 113 +/- 3 mm Hg, p less than 0.05) and within glomerular capillaries (55 +/- 2 vs 48 +/- 1 mm Hg, p less than 0.05), resulting in an increase in the transglomerular hydrostatic pressure gradient (40 +/- 2 vs 33 +/- 1 mm Hg, p less than 0.05). The glomerular capillary permeability coefficient, however, was decreased in the hypertensive rats (0.063 +/- 0.017 vs 0.115 +/- 0.011 nl/s/g kw/mm Hg, p less than 0.05), resulting in no change in nephron filtration rate 38.9 +/- 2.3 vs 39.0 +/- 2.5 nl/min/g kw). Nephron plasma flow also remained unchanged (154 +/- 10 vs 140 +/- 7 ml/min/g kw). In separate studies in this model of hypertension, saralasin infusion demonstrated a peripheral effect of circulating angiotensin II which was increased over controls. Kidney mass and GFR were not different between clipped and unclipped kidneys. No consistent abnormalities were observed by light or electron microscopy either in glomeruli or in vessels in the unclipped kidney. This study demonstrates that glomerular hemodynamics may be altered early in the course of modest hypertension in this model without altering blood flow or filtration rate. The decrease in glomerular capillary area and/or permeability (LpA) in the hypertensive rats could be either a result of the increased effect of circulating angiotensin II or the direct effect of glomerular capillary hypertension.
Influence of converting enzyme inhibition on renal hemodynamics and glomerular dynamics in sodium-restricted dogs.
Authors: Navar L G , Jirakulsomchok D , Bell P D , Thomas C E , Huang W C
Published: June 2012

Clearance and micropuncture experiments were performed to evaluate the influence of converting enzyme inhibition (CEI) (SQ 14,225) on renal hemodynamics, glomerular filtration rate (GFR), segmental vascular resistances, and superficial nephron function in anesthetized sodium restricted dogs. In one series (n = 8), renal blood flow (RBF) and GFR exhibited a high degree of autoregulatory efficiency when renal arterial pressure (RAP) was reduced from 126 +/- 5 to 86 +/- 1 mm Hg. With RAP maintained at the reduced level, CEI elicited increases in RBF (3.9 +/- 0.3 to 5.8 +/- 0.5 ml/min per g kw) and GFR (0.81 +/- 0.03 to 0.94 +/- 0.04 ml/min per g kw). With return of RAP to spontaneous levels during continued CEI, RBF and GFR autoregulatory efficiency was maintained, and was similar to that observed in control dogs subjected to the same procedures (n = 5). In the micropuncture experiments (n = 12), RAP was maintained at the reduced level (87.5 +/- .9 mm Hg), and measurements were made before and during CEI. Proximal tubule pressure, peritubular capillary pressure, stop flow pressure, and single nephron GFR (SNGFR) increased significantly. Regression analysis suggested that the increases in SNGFR were associated with small increases in the filtration coefficient. CEI reduced preglomerular resistance by 29% to 35% and efferent arteriolar resistance by 24% to 32%. These results indicate that the increased activity of the renin-angiotensin system that occurs during salt restriction exerts approximately equivalent vasoconstrictor influences on both preglomerular and postglomerular vascular resistance elements.
Surgical reversal of two-kidney one clip hypertension during inhibition of the renin-angiotensin system.
Authors: Russell G I , Bing R F , Thurston H , Swales J D
Published: June 2012

Conscious rats with two-kidney one clip Goldblatt hypertension had the constricting clip removed during continuous infusion of either dextrose, saralasin, or captopril. Other dextrose-infused animals underwent removal of the ischemic kidney or a sham procedure. Direct arterial blood pressure (BP) was recorded throughout the 15-hour preoperative and subsequent 24-hour postoperative period. Rats were studied in the "early" phase (1-3 weeks duration) or "chronic" phase (greater than 4 months) of hypertension. Animals subjected to a sham procedure returned to preoperative BP values. The BP of animals unclipped or nephrectomized did not return to previous hypertensive levels. Instead, a biphasic response was seen where BP partially recovered from an operative fall and then slowly declined to normal at 24 hours; this effect occurred in both stages of hypertension. At 24 hours, removal of the ischemic kidney was as effective as removal of the constricting clip in the correction of both early and chronic phase hypertension. Rats infused with saralasin or captopril demonstrated an acute (within 2 hours) and sustained fall in BP, but not to normotensive levels. This fall was significant in all animals (p less than 0.01) apart from chronic phase rats infused with saralasin where no significant fall was seen. Although animals infused with saralasin or captopril commenced at a lower preoperative BP, the biphasic pattern of response to unclipping was identical to that of dextrose-infused unclipped rats. Thus, sustained inhibition of the renin-angiotensin system did not modify the correction of hypertension produced by removal of the constricting clip, and the response to surgical correction did not appear to be entirely mediated by changes in the activity of the renin-angiotensin system, particularly in the chronic stage. Equally, the rapidity of correction is not consistent with a role of vascular hypertrophy.
Cognitive processes in hypertension.
Authors: Franceschi M , Tancredi O , Smirne S , Mercinelli A , Canal N
Published: June 2012

In 15 normotensive subjects, 17 newly diagnosed, untreated hypertensive patients, and 22 effectively treated hypertensive patients, a battery of neuropsychological tests was given. All subjects were neurologically asymptomatic. The neuropsychological battery included tests evaluating global cognitive functions (Card Sorting Test, Wechsler Memory Scale, Progressive Matrices 1938), as well as specific cognitive functions (Benton Test, subtests of the Wechsler-Bellevue Scale). Normotensive controls obtained better scores in all the tests. Statistical analysis of th scores suggests that hypertension is highly correlated with impairment of memory, logical reasoning, visuospatial organization, and attention. Therapy seems to impair attention, while the duration of disease seems to influence visuospatial performances.
Effects of isometric exercise on the carotid baroreflex in hypertensive subjects.
Authors: Mancia G , Ferrari A , Gregorini L , Parati G , Pomidossi G
Published: June 2012

Previous studies indicate that arterial baroreceptor modulation of heart rate is drastically reduced during static or dynamic exercise. We have investigated whether this reduction also occurs with regard to blood pressure modulation by the baroreflex. The study was performed in 19 subjects with uncomplicated untreated essential hypertension in whom blood pressure was measured intraarterially, and R-R interval was obtained by an electrocardiogram. The carotid baroreceptors were stimulated by neck suction of 30 seconds' duration, and equal stimuli were applied at rest and during hand-grip exercise performed at 40% of the subjects' maximal strength. Baroreceptor stimulation at rest increased R-R interval and reduced blood pressure. During hand-grip, the R-R interval responses to the baroreceptor stimulus were diminished by 61%. In contrast, the blood pressure responses were not significantly altered. Similar results were obtained when two subgroups of subjects with a lesser or greater degree of hypertension were separately considered. Thus, the carotid baroreceptor influence on blood pressure is largely preserved during exercise in contrast to the carotid baroreceptor influence on the sinus node, which is markedly impaired.
Reserpine and breast cancer in the Hypertension Detection and Follow-Up Program.
Authors: Curb J D , Hardy R J , Labarthe D R , Borhani N O , Taylor J O
Published: June 2012

Recent reports on the efficacy of pharmacological management in reducing mortality associated with mild hypertension have enhanced the importance of increasing our knowledge about drug toxicity. The Hypertension Detection and Follow-Up Program (HDFP) provides a convenient setting in which to examine the association reported between reserpine usage and breast cancer. In the intensively treated and followed group (Stepped Care [SC]), the relative breast cancer experience of those who did take reserpine and those who did not was examined. Of 2529 females in SC, 1036 received reserpine, with an average exposure of 1.97 years during 5 years of follow-up. Through extensive investigation, 21 cases of breast cancer were identified. using a life table regression method of analysis to adjust for actual time of reserpine exposure, race, sex, and medication status at entry, and comparing those who took reserpine with those who did not, the author's calculated a risk ratio of 1.28, with a confidence interval of 0.58 to 2.80. Adjustment for a number of other variables known to have relationships to breast cancer did not appreciably change the results. Thus, with certain precautions, the authors conclude that in this setting there is no indication of the recently postulated association of reserpine and the short-term enhancement of breast tumor growth.
Urinary prostaglandins in the Lyon strains of hypertensive, normotensive, and low blood pressure rats.
Authors: Benzoni D , Vincent M , Sassard J
Published: June 2012

A longitudinal study of the urinary excretion of prostaglandins (PGs) E and F alpha was performed in simultaneously selected hypertensive (LH), normotensive (LN), and low blood pressure (LL) female rats of the Lyon strains aged from 5 to 45 weeks. The urinary excretion of PGE did not significantly differ between LL and LN rats whereas in LH rats it was found to be significantly lower than that of LN or LL rats starting at the age of 32 weeks. The urinary excretion of PGF alpha was significantly reduced in both LL and LH rats; however, this decrease was more marked in LH than in LL animals and, from 9 weeks of age, the urinary PGF alpha were significantly lower in LH than in age-matched LL rats. In addition, both PGE and PGF alpha were found to be significantly and negatively related to the systolic blood pressure level in LH rate (r = -0.56, n = 58, p less than 0.001 for PGE; and r = -0.78, n = 58, p less than 0.001 for PGF alpha) but not in LN of LL animals. In conclusion, it seems unlikely that renal PGs could play a primary role in the spontaneous hypertension observed in the Lyon strain of rats.
Comparison of two automatic blood pressure recorders and the mercury sphygomomanometer.
Authors: Voors A W , Sklov M C , Halperin H , Webber L S , Berenson G S
Published: June 2012

The Physiometrics automatic blood pressure recorder was compared with the mercury sphygmomanometer in 2200 children aged 5-14 years, each reexamined after 3 and 5 years; the Physiometrics recorder produced higher intrachild correlations. In trials we could transfer what were essentially Physiometrics readings into levels similar to mercury sphygmomanometric readings by filtering out the infrasonic frequency band. The Physiometrics USM-105 was compared with its successor, the Physiometrics SR-2, on 378 children aged 10-17 years. The SR-2 measured lower than the USM-105: 4.1 mm Hg systolic and 8.5 mm Hg diastolic; differences were larger in the younger children. Both in mean levels and correlations, SR-2 readings were closer to the mercury sphygmomanometer's than were USM-105 readings, except or diastolic SR-2 readings, which were farther below the mercury sphygomomanometer 4th-phase readings than the USM-105. However, the SR-2 readings are likely closer to the true diastolic pressure in children 13 years and older, although we did not measure pressures intraarterially. Disc readings for systolic pressures showed coefficients of correlation averaging 0.96 among (n = 168) and 0.98 within (n = 40) readers for both models, but diastolic readings showed marked improvement form USM-105 (0.73, 0.81) to SR-2 (0.91, 0.97). In many of the parameters observed, SR-2 constitutes an improvement over USM-105. Automatic recorders offer certain advantages for measuring blood pressure in large-scale epidemiologic studies.
Characterization of antibodies to canine renal renin. Studies of interspecies homology of renin using antibodies as probe.
Authors: Dzau V J , Brenner A , Wolfsohn S , Haber E
Published: June 2012

Antibodies raised to pure canine renal renin were used to probe homology of renin from other species. Goat, rabbit, and mouse antibodies exhibited similar properties and were specific for renin as confirmed by immunodiffusion, immunoelectrophoresis, and selective inhibition of renin enzymatic activity. Goat antibody also inhibited the enzymatic activities of rat, hog, and bovine renin. Immunologic cross reactivity was further confirmed by direct binding and competition assays. Goat anti-(canine renin) antibody did not inhibit human or mouse renin activity, but readily bound to these enzymes, suggesting the presence of epitopes distant from the enzymatic site. Purified goat Fab retained only 10% to 20% of the anticatalytic activity of antibody, but this activity was largely recovered when donkey anti-goat antibody was added to the Fab-renin mixture. Thus, the major fraction (80% to 90%) of goat antibody exerted its anticatalytic activity by immune complex formation of steric hindrance and is not catalytic-site directed, whereas 10% to 20% binds an epitope at or near the catalytic site.
Behavioral consequences of mild hypertension.
Authors: Shapiro A P , Miller R E , King H E , Ginchereau E H , Fitzgibbon K
Published: June 2012

Tests made of the sensory-perceptual, cognitive, and psychomotor abilities of untreated young patients with essential hypertension have revealed a pattern suggesting a slight functional impairment of the central nervous system. Reduced performance was most marked for those tasks requiring speed and psychomotor coordination, particularly when the behaviors observed were self-initiated. Lowered scores were more evident among female hypertensives; no differences in performance by race were noted. The deficits measured by these sensitive tests do not appear to be great enough to intrude on everyday activity nor to impair work ability. Changes that may result from blood-pressure-lowering therapies will require further study.
A genetic locus (Hyp-2) controlling vascular smooth muscle response in spontaneously hypertensive rats.
Authors: Rapp J P
Published: June 2012

Aortic vascular smooth muscle from spontaneously hypertensive rats (SHR) is known to respond in vitro to nonphysiologic cations with greater contraction than vascular smooth muscle from certain normotensive control stocks. The pattern of inheritance of the response of aortic rings to cobalt (Co2+) in vitro was determined. The test characteristic utilized was the cobalt response ratio (CRR) defined as the contractile response to 0.6 microM Co2+ divided by the response given by maximal stimulation with 10 microM Co2+. The SHR were crossed with Dahl salt-resistant rats that had been inbred for 21 generations (R/JR strain) to produce F1, F2, and backcross populations. The CRR was 0.90 +/- 0.011 in SHR, 0.74 +/- 0.016 in F1, and 0.38 +/- 0.031 in R/JR. The F1 value was significantly higher than the midparental value indicating partial SHR dominance. The F1 males from reciprocal crosses had similar CRR indicating no sex-linked effect. In the backcross to the R/JR, the CRR showed a bimodal distribution segregating one intermediate type: one R/JR type. In the backcross to the SHR the CRR showed a unimodal distribution. In F2 rats there was a bimodal distribution segregating three intermediate type: one R/JR type. In F2 rats there was a significant (p less than 0.005) blood pressure difference of 9.7 mm Hg between phenotypes. It is concluded that there is an autosomal locus (named "Hyp-2" for hypertension locus number 2) controlling vascular smooth muscle response to Co2+, which exhibits partially dominant inheritance. Alleles at Hyp-2 segregate with an increment in blood pressure.
Cardiovascular responses to isometric exercise and standing in normotensive subjects during converting enzyme inhibition with teprotide.
Authors: Niarchos A P , Pickering T G , Laragh J H
Published: June 2012

The hemodynamic responses to isometric exercise (hand grip) were investigated in normotensive subjects during a 150 mEq (n = 8) sodium diet and a 10 mEq (n = 6) sodium diet both before and after the administration of the converting enzyme inhibitor teprotide. Although teprotide significantly decreased the mean arterial pressure during both sodium intakes, the normal pattern of hemodynamic response to hand grip was preserved, that is mean arterial pressure was increased by hand grip mainly because of an increase in cardiac output. Changes of plasma catecholamines during hand grip were not affected by teprotide. In addition, the hemodynamic responses to standing were not substantially altered by teprotide. When fainting occurred (in the seated position) following the administration of teprotide, it was associated not only with a decrease in arterial pressure but also with a concurrent reduction in cardiac output. We conclude that angiotensin inhibition by teprotide does not significantly impair sympathetically mediated cardiovascular responses.
Proteins binding to kallikrein and esterase A2 in the urine of salt-sensitive and salt-resistant rats.
Authors: Rapp J P , Joseph M K , McPartland R P
Published: June 2012

Iodine-labeled ([125I]) rat urinary kallikrein and rat urinary TAME esterase A2 were used as probes to look for urinary and plasma proteins that bind to these enzymes. Such proteins are presumptive enzyme inhibitors. Complexes formed with labeled enzymes were identified by polyacrylamide gel electrophoresis followed by autoradiography. Urine from young (6 weeks old) Dahl salt-sensitive (S) rats showed no, or only traces, of protein binding to kallikrein. Concomitant with the slow development of hypertension and proteinuria in S rats fed normal rat chow, one of the six kallikrein-binding proteins demonstrable in plasma was readily found in S-rat urine. This kallikrein-binding protein was called "KBP-1." R rats showed either no or much less KBP-1 in the urine, compared to S rats up to 5 months of age. A partly purified preparation of KBP-1 was shown to inhibit the TAME esterase activity of rat urinary kallikrein in the radiometric TAME assay. Urine of proteinuric S rats also contained two TAME esterase-binding proteins, TEBP-1 and TEBP-2, detected with the [125I]-esterase A2 probe. As S rats aged from 3 to 8 months, free KBP-1 disappeared from the urine in spite of increased and marked proteinuria and the continued presence of KBP-1 in plasma. Concomitant with this age-related loss of urinary KBP-1 there was a marked shift in S urinary proteins binding to [125I]-esterase A2 from TEBP-1 to TEBP-2. It was speculated that KBP-1 and TEBP-1 were the same protein detectable with either labeled kallikrein or labeled esterase A2. The concomitant disappearance of free KBP-1 (TEBP-1) and the appearance of free TEBP-2 in the urine of old, hypertensive, proteinuric S rats suggests that: 1) most of the KBP-1 (TEBP-1) is bound to enzyme(s) in old rats; or 2) KBP-1 (TEBP-1) is largely converted to TEBP-2 in old rats; or 3) both are true and that binding of KBP-1 (TEBP-1) to enzymes is associated with the generation of TEBP-2.
Evidence for a vascular sensitizing factor in plasma of saline-loaded dogs.
Authors: Plunkett W C , Hutchins P M , Gruber K A , Buckalew V M
Published: June 2012

This study investigates whether plasma extracts previously demonstrated to have natriuretic and antinatriferic activity have effects on vascular reactivity of rat cremaster arterioles. Plasma from hydropenic and saline-loaded dogs was subjected to Diafiltration, and eluted on a strong cation exchange column (SCX). The effects of intraarterial injections of various column fractions on constrictor responses to repeated injections of 33.3 ng of norepinephrine (NE) were used to indicate changes in vascular responsiveness in third order cremaster arterioles. SCX fraction I (void volume) from saline-loaded dogs (FI-S) caused an increase in constrictor response to NE of 101%. Increased vascular responsiveness peaked at 40 minutes and remained significantly elevated (p less than 0.05) for 130 minutes. Fraction I from plasma of hydropenic dogs (FI-H) and fraction III from plasma of saline-loaded dogs (FIII-S) did not increase vascular responsiveness to NE. FI-S shifted the dose response curves for NE, arginine vasopressin, and angiotensin II parallel and to the left relative to control by a factor of 3.05-, 2.95-, and 5.63-fold, respectively, at the 50% constrictor dose. Systemic injections of FI-S, but not FI-H, caused a 10 mm Hg rise in blood pressure at 50 minutes, and blood pressure was significantly elevated for 30 to 90 minutes after injection (p less than 0.01). These data demonstrate a vascular-sensitizing factor in FI-S. The factor appears in the same chromatographic fraction previously demonstrated to contain natriuretic, antinatriferic, and digoxin-like activity. The correlation of these activities with salt loading suggests they are due to the same substance, which may be the putative natriuretic hormone.
Baroreceptor reflex influence on peripheral circulations in salt-loading hypertension in dogs.
Authors: Liard J F , Silenzio R
Published: June 2012

To determine the importance of cardiovascular reflexes in the vasodilation found in skeletal muscle in the early stages of salt-loading hypertension in dogs, we gave for several days an intravenous infusion of isotonic sodium chloride, 190 ml/kg/day, to seven dogs with their renal mass reduced following extensive destruction of their arterial baroreceptor afferents. Mean arterial pressure, cardiac output (electromagnetic flowmeter), and regional blood flows (radioactive microspheres) were measured sequentially and the results compared with those obtained in five control dogs. The salt-loaded animals exhibited an increase in cardiac output and in arterial pressure on the first day of infusion. Blood flow to the splanchnic area, the skin, the bone, the skeletal muscle, the heart, the lungs and the brain increased significantly, but vascular conductance was unchanged in most territories, including skeletal muscle. After 5 to 7 days, cardiac output returned toward control values, but pressure remained elevated. Apart from the myocardium, the regional blood flows were normalized and the conductances were decreased. These results indicate that cardiovascular reflexes are responsible for the transient early vasodilation in skeletal muscle which characterizes salt-loading hypertension in intact animals.
Potassium relaxation of vascular smooth muscle from DOCA hypertensive pigs.
Authors: Webb R C
Published: June 2012

This study was designed to characterize potassium-induced relaxation in vascular smooth muscle during the development of deoxycorticosterone acetate (DOCA) hypertension. Pigs were implanted subcutaneously with 100 mg/kg DOCA. Mean arterial pressure in the DOCA-treated pigs reached levels approximately 37% greater than controls. In some pigs, the left hindlimb vascular bed was "protected" from the rise in arterial pressure by ligation of the iliac artery. Arterial strips from DOCA hypertensive and normotensive pigs relaxed in response to potassium after contraction induced by norepinephrine in potassium-free solution. Arterial strips from DOCA hypertensive pigs showed greater relaxation than did those from normotensive pigs. The magnitude of relaxation in femoral arteries from "protected" hindlimbs was similar to that in arteries from the contralateral unoccluded limb. Potassium-induced relaxation in tail arteries from DOCA hypertensive pigs was more sensitive to ouabain inhibition than that from normotensive pigs. Relaxation induced by potassium varied with: 1) length of incubation in potassium-free solution; 2) concentration of added potassium; and 3) concentration of norepinephrine added during the potassium-free interval. The amplitude of potassium-induced relaxation is believed to be a functional index of the activity of the electrogenic sodium-potassium transport system. These experiments support the hypothesis that vascular smooth muscle from DOCA hypertensive animals has increased electrogenic sodium pump activity. The development of this vascular change parallels the increase in blood pressure induced by mineralocorticoid excess.
Effect of alterations in extracellular fluid volume on urinary kallikrein in the conscious rat.
Authors: Marks E S , Frech M , Proud D , Keiser H R
Published: June 2012

The effect of alterations in extracellular fluid volume (ECV) and solute concentration on excretion of urinary kallikrein was examined in conscious Sprague-Dawley rats. Animals were given infusions of either dextrose and water, saline, or albumin according to a variety of protocols. These were designed to evaluate possible relationships between excretion of kallikrein, volume, sodium, and potassium. A reproducible pattern of kallikrein excretion was noted in all volume expanded groups. This consisted of a short lived increase during the initial hour of expansion with a subsequent fall to lower levels than baseline and a gradual recovery. To define the role of aldosterone in these studies, an adrenalectomized group and a group of appropriately prepared sham controls were expanded with saline. Adrenalectomy did not effect this pattern. We postulate a tubular "washout" phenomenon as the etiology of these observations. Results of these studies fail to demonstrate a consistent relationship between urinary volume, sodium, or potassium and the simultaneous amount of kallikrein found in the urine.
Methionine enkephalinergic neuronal activity in cerebral nuclei of spontaneously hypertensive rats.
Authors: Nakamura K , Hayashi T
Published: June 2012

The role of methionine enkephalin (ME) neurons in the development of genetic hypertension in SHR is the subject of this study. Methionine enkephalin-like immunoreactivity (MELI) and ME receptor binding (MERB) levels were assayed quantitatively by microdensitometry of fluorescence micrographs and autoradiographs of 85 cerebral nuclei and areas of both young and adult spontaneously hypertensive rats (SHR). Normotensive Wistar Kyoto rats (WKY) were used as controls. In young SHR, both MELI and MERB levels were markedly higher in the n. dorsalis nervi vagi, n. amygdaloideus medialis, and group of stria terminal nuclei than in those of young WKY, while both levels were lower in the n. reticularis lateralis, n. corporis mamillaris lateralis, and n. arcuatus. MELI levels in the tractus spinalis nervi trigemini and MERB in the n. tractus spinalis nervi trigemini and median eminence were also lower in young SHR, whereas MERB in the n. amygdaloideus centralis was higher. Alteration in these nuclei was no longer detectable in adult SHR. Whereas in adult SHR, both MELI and MERB levels in the n. reticularis medialis were higher than those of adult WKY, and MELI in the n. accumbens septi and MERB in the n. caudatus were also higher, while MELI in the area lateralis hypothalami was lower than that in adult WKY. The findings indicate that activation of ME neurons in the n. dorsalis nervi vagi and limbic area and also a decrease in ME neuronal activity in the area spinalis nervi trigemini, n. reticularis lateralis, and n. arcuatus may be casually related to the development of hypertension and hyperreactivity in SHR.
Blood pressure and hormone changes associated with weight reduction in the obese.
Authors: Sowers J R , Nyby M , Stern N , Beck F , Baron S , Catania R , Vlachis N
Published: June 2012

This study examines factors modulating blood pressure reduction in obese patients undergoing weight reduction on a low calorie protein diet. Plasma norepinephrine (NE) was correlated (r = 0.65, p less than 0.01) with blood pressure in 20 obese patients prior to weight loss. Reductions in blood pressure levels following upright posture and isometric handgrip exercise were related to reduction in NE levels after these maneuvers. While plasma epinephrine levels declined in parallel with NE levels, plasma dopamine actually increased (p less than 0.05) during the first 2 weeks of caloric restriction. Prior to weight loss the obese patients demonstrated a significant rise in prolactin levels following posture and exercise, but following caloric restriction this was not observed. Levels of plasma renin activity (PRA) and aldosterone obtained after posture and exercise maneuvers were reduced after 8 weeks of caloric restriction, and reductions in PRA were related to reductions in NE (r = 0.56, p less than 0.01). Reductions in blood pressure in association with caloric restriction in these obese patients seems to result, in part, from reduced sympathetic nervous system activity as well as secondary effects of reduced adrenergic activity on renal sodium excretion and the renin-angiotensin-aldosterone axis.
Essential hypertension: sodium-lithium countertransport in erythrocytes from patients and from children having one hypertensive parent.
Authors: Ibsen K K , Jensen H A , Wieth J O , Funder J
Published: June 2012

This report deals with the possibility that there is a specific change of the lithium transport across the membrane of erythrocytes from patients with essential hypertension. Sodium-lithium countertransport was significantly increased (p less than 0.005) in erythrocytes from 17 males with essential hypertension (mean 0.7 mmole (liter cells X hr)-1, range 0.4-1.6) compared to a group of 16 normotensive males (mean, 0.4 mmole (liter cells X hr)-1, range 0.3-0.6). A considerable overlap between the values from patients and controls was found. No significant increase of the transport function was found in a group of 14 female patients (mean 0.4 mmole (liter cells X hr)-1, range 0.2-0.6) compared with 10 normotensive female controls (mean 0.3 mmole (liter c hr)-1, range 0.3-0.6). A considerable overlap between the values from patients and controls was found. No significant increase of the transport function was found in a group of 14 female patients (mean 0.4 mmole (liter cells X hr)-1, range 0.2-0.6) compared with 10 normotensive female controls (mean 0.3 mmole (liter c hr)-1, range 0.3-0.6). A considerable overlap between the values from patients and controls was found. No significant increase of the transport function was found in a group of 14 female patients (mean 0.4 mmole (liter cells X hr)-1, range 0.2-0.6) compared with 10 normotensive female controls (mean 0.3 mmole (liter cells X hr)-1, range 0.1-0.6). Determination of sodium-lithium countertransport in red blood cells from nine children with and 14 without known familial disposition for essential hypertension did not demonstrate a close coupling between genetic disposition and the membrane transport function. In spite of the very small intraindividual variability of the transport function, studies of changes in sodium-lithium counter-transport are hampered by considerable interindividual variability of the transport in red cells from apparently normal individuals.
Antihypertensive drug treatment in a middle-aged population.
Authors: Enlund H , Nissinen A , Tuomilehto J
Published: June 2012

In Finland's North Karelia region a community-based program for control of hypertension was administered for 5 years. Afterward, drug treatment and the impact of such treatment on control of blood pressure were studied in a cross-sectional survey. The study population (n = 10,199) consisted of a 6.6% random sample of people aged 30-64 years in North Karelia (program area) and Kuopio (reference area). Rate of participation was about 90%. The methods included questionnaire, personal interview, and clinical examination. In North Karelia, 24% of the men and 25% of the women were hypertensives (blood pressure greater than or equal to 175 mm Hg systolic and/or 100 mm Hg diastolic, or currently on antihypertensive drug therapy), compared with 33% of the men and 29% of the women in the reference area. In North Karelia, 48% of the male hypertensives and 67% of the female hypertensives were on drug therapy, compared with 32% and 54%, respectively, in the reference area. Of the total population in each area, 14% in North Karelia currently used drugs, compared with 13% in the reference area. Diuretics and beta-blockers were the drugs most commonly prescribed; men used beta-blockers more often than women did. In terms of quantity of medication, type of drugs, and compliance, the differences between the two areas were small. Control of blood pressure, however, was clearly better in North Karelia than in the reference area for hypertensives and drug users and for both men and women. Therefore, compared with the traditional system, organized hypertension care results in more successful treatment.
Contribution of the sympathetic nervous system to the hypertensive effect of a high sodium diet in stroke-prone spontaneously hypertensive rats.
Authors: Dietz R , Schömig A , Rascher W , Strasser R , Lüth J B , Ganten U , Kübler W
Published: June 2012

In stroke-prone spontaneously hypertensive rats (SHRSP) plasma norepinephrine levels and vascular reactivity to norepinephrine are increased and intravascular volume is reduced during the developmental phase of hypertension. Since the accelerated rise in blood pressure following sodium-loading in SHRSP cannot be attributed to the volume-retaining properties of sodium, the effects of an increased dietary intake of sodium on biochemical parameters of sympathetic vascular tone were investigated. The following results were obtained. First, the increased reactivity of vascular smooth muscle was further augmented in sodium-treated SHRSP; the degree of supersensitivity was positively correlated to the plasma sodium concentration. After blockade of the neuronal uptake by 30 microM cocaine, no difference in vascular reactivity to norepinephrine was detected between SHRSP on a normal and SHRSP on a high-sodium diet. Second, the inactivation of norepinephrine by the neuronal uptake was impaired in rats on a high-sodium diet, the impairment being more pronounced in SHRSP than in Wistar-Kyoto (WKY) rats. This decreased inactivation could be expected to cause higher concentrations of the neurotransmitter at the receptor site if the transmitter release from the nerve ending remains constant. Third, the release of norepinephrine and epinephrine into the plasma was increased in sodium-loaded SHRSP but not in sodium-loaded WKY. Cold exposure exaggerates these differences between normotensive and hypertensive rats. These findings suggest that a high-sodium intake modifies the transmission of sympathetic impulses at the level of the nerve terminal in both WKY and SHRSP. In the normotensive rats, moderate impairment of norepinephrine inactivation, however, was balanced by an appropriate reduction in central sympathetic discharge following sodium-loading. In the hypertensive rats, the peripheral disturbance in norepinephrine inactivation due to sodium-loading was obviously not balanced by an adequate withdrawal of central sympathetic discharge. The resultant hemodynamic change was a further increase in the sympathetically mediated vasoconstriction, which is regarded as at least one of the main mechanisms of the sodium-dependent acceleration of hypertension in SHRSP.
Hypertension and neurofibromatosis. Case report.
Authors: Guthrie G P , Tibbs P A , McAllister R G , Stevens R K , Clark D B
Published: June 2012

A 14-year-old girl with neurofibromatosis presented with severe hypertension. She was subsequently found to have a cerebellar glioblastoma multiforme and vascular lesions producing coarctation of the abdominal aorta and 50% and 95% stenosis of the left and right renal arteries respectively. No evidence of pheochromocytoma was found. After removal of the cerebellar tumor, marked amelioration of the hypertension suggested that the tumor had a major role in the pronounced elevation of her blood pressure. Patients who have both neurofibromatosis and hypertension should be carefully evaluated for these several potential lesions.
Systolic time intervals as possible predictors of pressure response to sustained beta-adrenergic blockade in arterial hypertension. A within-patient, placebo-controlled study.
Authors: Verdecchia P , Brignole M , Delfino G , Queirolo C , De Marchi G , Bertulla A
Published: June 2012

Systolic time intervals (STI) were recorded at rest and during isometric exercise (IHG) in 20 hypertensive outpatients, WHO Stage 1 or 2. In a double-blind crossover study, slow-release metoprolol 200 mg once daily and matched placebo were given for 4 weeks each, at the end of a 2-week placebo washout. Blood pressure and STI were taken in the last day of washout and of either crossover period. Treatment decreased blood pressure and heart rate values at rest and on peak IHG; it didn't modify preejection period index (PEPI), left ventricular ejection time index (LVETI), and their ratio at rest, but decreased the ratio between diastolic blood pressure and PEPI (DBP/PEPI ratio) at rest and on peak IHG and lengthened the PEPI at peak IHG. Resting PEPI values on placebo treatment showed a negative correlation with systolic (r = -0.72) as well as diastolic (r = -0.80) pressure reduction on slow-release metoprolol as compared with placebo treatment. The PEP/LVET ratio at rest on placebo treatment showed a negative correlation with systolic (r = -0.78) as well as diastolic (r = -0.82) pressure reduction at rest on metoprolol compared with placebo treatment. Patients with a resting PEP/LVET ratio less than 0.43 showed a reduction in both systolic and diastolic pressure approximating or exceeding 20 mm Hg, whereas patients with a PEP/LVET ratio greater than 0.47 showed a decrease in systolic and diastolic blood pressure of less than 10 mm Hg. In patients with a PEP/LVET ratio of 0.43 to 0.47 (50% of the trial population), STI didn't show any correlation with the pressure response to beta-blockade. A positive correlation was found between the DBP/PEPI ratio at rest on placebo treatment and systolic (r = 0.56) as well as diastolic (r = 0.76) pressure reduction at rest on slow-release metoprolol compared with placebo treatment. Thus, STI appeared as promising predictors of the magnitude of blood pressure response to sustained beta-blocking therapy in mild-to-moderate essential hypertension, mostly in patients with a resting PEP/LVET ratio less then 0.43 or greater then 0.47.
Increase in plasma renin in aggressive mice originates from kidneys, submaxillary and other salivary glands, and bites.
Authors: Poulsen K , Pedersen E B
Published: June 2012

Aggressive behavior in mice caused a vast release of renin into the plasma. The present data support previous findings that the main sources were the submaxillary gland and kidney. In addition, unidentified salivary glands capable of releasing renin into the saliva were demonstrated by alpha-adrenergic stimulation. The role of these glands in generating plasma renin is unknown. Experiments were performed that strongly support the possibility that aggression-provoked salivary renin may be transferred by bites from one animal to another.