bluuebunny/crossref_metadata_2025 huggingface dataset:
Blood pressure change and survival after age 75.
Authors: Langer R D , Criqui M H , Barrett-Connor E L , Klauber M R , Ganiats T G
Published: June 2012

Higher diastolic pressure predicted better survival in men 75 years or older in two prior analyses in the Rancho Bernardo population. Diastolic change was implicated as a possible explanation. We studied this by assessing survival according to blood pressure change in 795 men and women aged 75 years and older at the time of a second measurement taken an average of 11 years after the first, who were then followed for 5 years. Sex-specific analyses compared participants with a diastolic decrease of 5 mm Hg or greater and participants with a systolic decrease of 10 mm Hg or greater with those whose blood pressure levels did not change or increased. In men, after adjustment for baseline pressure, a decrease in diastolic pressure of 5 mm Hg or greater was associated with higher all-cause mortality (relative risk, 2.33; 95% confidence interval, 1.39 to 3.91) and cardiovascular mortality (3.13, 1.47 to 6.66). The mortality risk was strongest in men who took antihypertensive medication and had a fall in diastolic pressure (12.33, 2.73 to 55.72) compared with treated men whose pressures did not decrease. Among men with isolated systolic hypertension, those treated whose diastolic pressure remained stable had the best survival. A systolic fall in men and a decrease in either diastolic or systolic in women was not associated with poorer survival after adjustment for baseline pressure. We conclude that a fall in diastolic pressure of 5 mm Hg was associated with poor survival in men after age 75. This risk was strongest in men who took antihypertensive medication.
Arterial smooth muscle cell phenotype in stroke-prone spontaneously hypertensive rats.
Authors: Contard F , Sabri A , Glukhova M , Sartore S , Marotte F , Pomies J P , Schiavi P , Guez D , Samuel J L , Rappaport L
Published: June 2012

The aim of this study was to determine the phenotype of smooth muscle cells in the arteries of chronically hypertensive animals and to analyze the effects of treatments known to increase the survival of the animal without a clear effect on its hypertensive state. Stroke-prone spontaneously hypertensive rats (SHRSP) kept on a 1% sodium drinking solution were untreated or treated with one of two diuretics, indapamide (3 mg/kg per day) or hydrochlorothiazide (20 mg/kg per day), from 6 to 13 weeks of age. Phenotype was characterized by the immunolabeling of arteries with antibodies raised against a cellular form (EIIIA) of fibronectin, alpha-smooth muscle actin, and nonmuscle myosin. We demonstrated that phenotypes of smooth muscle cells of the SHRSP differ from those found in Wistar-Kyoto rats. The difference in phenotype is specific for the vessel type: ie, an increased expression of nonmuscle myosin in the aorta and of both EIIIA fibronectin and nonmuscle myosin in the coronary arteries. The two diuretics (1) had no effect on blood pressure, (2) prevented or did not prevent the increase in medial thickness, and (3) prevented changes in both smooth muscle cell phenotype and ischemic tissular lesions. Taken together, the results suggest that in SHRSP the changes in the phenotype of smooth muscle cells and the thickness of arteries are unrelated events. We propose that the maintenance of the contractile phenotype of the arterial smooth muscle cells could be an essential parameter involved in the prevention of the deleterious consequences characteristic of a severe hypertensive state.
Angiotensin II increases norepinephrine release from atria by acting on angiotensin subtype 1 receptors.
Authors: Brasch H , Sieroslawski L , Dominiak P
Published: June 2012

Norepinephrine stores in electrically driven guinea pig isolated atria were loaded with [3H]norepinephrine, and norepinephrine release was deduced from the radioactivity efflux. Electrical field stimulation of sympathetic nerve endings was applied during the refractory period of atrial contractions. The stimulation-induced release of norepinephrine was increased by angiotensin II (Ang II) (10(-8) to 10(-6) mol/L) in a concentration-dependent manner. The maximum observed effect was a 55% augmentation. The effects of 10(-7) and 10(-6) mol/L Ang II were abolished by 10(-6) and 10(-5) mol/L of the subtype 1 Ang II receptor antagonist losartan, respectively. Losartan by itself (10(-6) mol/L) caused a 14% reduction of norepinephrine release. The subtype 2 Ang II receptor ligand PD 123319 (1-[[4-(dimethylamino)-3-methylphenyl]methyl]-5-(diphenylacetyl)- 4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid ditrifluoroacetate) in a concentration of 10(-4) mol/L had no detectable influence on transmitter release and did not antagonize the effect of Ang II. Angiotensin I (10(-6) and 10(-5) mol/L) increased norepinephrine release maximally by 23%. This effect was antagonized by 10(-5) mol/L losartan and did not appear in the presence of 10(-6) mol/L of the converting enzyme inhibitor ramiprilat. These results suggest that Ang II increases norepinephrine release by an activation of subtype 1 receptors, whereas angiotensin I is converted to Ang II to become effective.
Normotensive blacks have heightened sympathetic response to cold pressor test.
Authors: Calhoun D A , Mutinga M L , Collins A S , Wyss J M , Oparil S
Published: June 2012

The purpose of this study was to compare sympathetic nerve activity responses to the cold pressor test in black and white normotensive subjects. We recorded muscle sympathetic nerve activity (microneurography of the peroneal nerve), arterial blood pressure, and heart rate in 9 normotensive American blacks (24 +/- 2 years, mean +/- SEM) and 10 normotensive American whites (28 +/- 2 years) at rest and during hand immersion in ice water (cold pressor test). Body weight was not different in the two groups (72.4 +/- 3.7 versus 74.1 +/- 3.8 kg, black versus white subjects). During supine rest, mean arterial pressure (92 +/- 2 versus 93 +/- 3 mm Hg, black versus white), heart rate (66 +/- 4 versus 62 +/- 3 beats per minute, black versus white), and muscle sympathetic nerve burst frequency (12 +/- 2 versus 17 +/- 3 bursts per minute, black versus white) were not different in the two groups. During the cold pressor test, mean arterial pressure, heart rate, and muscle sympathetic nerve activity increased from supine rest in both groups. The magnitudes of increases in mean arterial pressure and total minute muscle sympathetic nerve activity were significantly greater in blacks than whites (33.5 +/- 3 versus 22.4 +/- 3 mm Hg and 416 +/- 24% versus 243 +/- 31% of control, respectively, black versus white, P < .05). The increases in heart rate were most significantly different for the two groups. These data suggest that the enhanced pressor response to cold stress observed in normotensive blacks is attributable to greater increases in peripheral sympathetic nerve activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Arterial hemodynamics in human hypertension. Effects of angiotensin converting enzyme inhibition.
Authors: Ting C T , Yang T M , Chen J W , Chang M S , Yin F C
Published: June 2012

Previous studies have shown some distinct hemodynamic alterations in essential hypertension, including increased resistance, wave reflections, and pulse wave velocity and decreased systemic compliance. These abnormalities are completely normalized by nonspecific smooth muscle dilation with nitroprusside but not by combined alpha- and beta-adrenergic blockade. The renin-angiotensin system, acting possibly via both circulating and local tissue effects, is thought to play an important role in essential hypertension, so its role in the altered hemodynamics deserves careful investigation. A hypertensive patient group was compared with a normotensive group similar in age, body size, and proportion of men and women. During diagnostic cardiac catheterization, ascending aortic micromanometer pressures and electromagnetic flows were measured in the baseline state. Intravenous captopril of a sufficient dosage (11 mg) to normalize blood pressure then was given to the hypertensive patients while measurements were repeated. From the pressures and flows, aortic input impedance, wave reflection magnitude, and compliance were computed. In the hypertensive group, the important hemodynamic alterations consisted of increased peripheral resistance, first zero crossing of aortic impedance phase angle, and wave reflections and decreased systemic compliance. Captopril had a pronounced hemodynamic effect. It normalized blood pressure, resistance, and impedance phase angle zero crossing. Compliance, although increased substantially by captopril, was still slightly lower than normotensive levels. The magnitude of wave reflections, although substantially lowered by angiotensin converting enzyme inhibition, was still persistently greater than normal. The present results, together with those previously reported, demonstrate that a complex interplay of factors underlies the increased smooth muscle tone in essential hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
Short-term variability of blood pressure and heart rate in borderline and mildly hypertensive subjects.
Authors: Takalo R , Korhonen I , Turjanmaa V , Majahalme S , Tuomisto M , Uusitalo A
Published: June 2012

Electrocardiogram and intra-arterial blood pressure were recorded in 96 men (aged 35 to 45 years) by the Oxford method over a 30-hour period. The study involved 33 normotensive, 29 borderline hypertensive, and 34 mildly hypertensive individuals, as assessed by the cuff method. Five-minute periods during sleep and with subjects in supine, sitting, and standing positions were extracted from the recordings for frequency domain analysis. Power spectrum density estimates of systolic blood pressure, diastolic blood pressure, and heart rate were calculated by an autoregressive method over the bandwidths of 0.02 to 0.075 (low-frequency), 0.075 to 0.15 (midfrequency), and 0.15 to 0.35 Hz (high-frequency), attributable to thermoregulatory, baroreceptor, and respiratory activity. No significant intergroup differences were observed at nighttime, but in different body positions the borderline hypertensive subjects frequently had either greater low-frequency variability or smaller midfrequency variability than the other groups. In this respect, the power spectra for systolic and diastolic blood pressures provided better statistical differentiation between the groups than those for heart rate. Furthermore, the borderline hypertensive subjects exhibited attenuated night-day changes in the low-frequency band for all time series. The results suggest that in borderline hypertension the baroreceptor oscillations are shifted to lower frequencies, presumably reflecting altered function of the sympathetic nervous system. In conclusion, spectral analysis of blood pressure variability for controlled test situations made it possible to detect differences in the cardiovascular regulatory systems between normotensive, borderline hypertensive, and mildly hypertensive individuals.
Effects of a beta-blocker or a converting enzyme inhibitor on resistance arteries in essential hypertension.
Authors: Schiffrin E L , Deng L Y , Larochelle P
Published: June 2012

Seventeen male untreated mild essential hypertensive patients aged 41 +/- 2 years agreed to participate in a double-blind randomized trial to test the effects of antihypertensive treatment on the structure and function of subcutaneous resistance arteries. Patients were treated with either 50 to 100 mg/d atenolol or 2.5 to 5 mg/d cilazapril. Blood pressure before treatment was 148 +/- 6/99 +/- 1 and 147 +/- 2/99 +/- 1 mm Hg, respectively. At 1 year of treatment blood pressure was 131 +/- 4/85 +/- 2 and 132 +/- 2/87 +/- 1 mm Hg, respectively. Resistance arteries (200 to 400 microns lumen diameter) dissected from subcutaneous gluteal biopsies obtained before treatment and at 1 year showed that the media-lumen ratio of arteries from patients treated with cilazapril was reduced to 6.31 +/- 0.21% from 7.54 +/- 0.31% before treatment (P < .05), still slightly but significantly larger (P < .05) than the media-lumen ratio of resistance arteries of normotensive control subjects (5.15 +/- 0.30%). In contrast, in arteries from patients treated with atenolol there was no significant change with treatment (7.97 +/- 0.60% before and 8.07 +/- 0.45% after 1 year of treatment). Active wall tension responses to endothelin-1 were blunted in hypertensive patients and normalized in the cilazapril-treated patients. Depressed active media stress responses to norepinephrine, arginine vasopressin, and endothelin-1 were accordingly normalized in the patients receiving cilazapril as the media width became thinner but were unchanged in those taking atenolol.(ABSTRACT TRUNCATED AT 250 WORDS)
Differential effects of digitalis on chemoreflex responses in humans.
Authors: Schobel H P , Ferguson D W , Clary M P , Somers V K
Published: June 2012

To investigate the effects of digitalis on chemoreflexes in humans, we measured muscle sympathetic nerve activity (microneurography), minute ventilation, oxygen saturation, end-tidal carbon dioxide, mean arterial pressure, heart rate, and central venous pressure during stimulation of peripheral chemoreceptors with hypoxia, during stimulation of central chemoreceptors with hypercapnia, and during a cold pressor test before and after digitalis and placebo in 10 healthy volunteers on two different days (randomized, double-blind, cross-over design). Digitalis did not affect baseline measurements significantly. Despite similar changes in oxygen saturation and end-tidal carbon dioxide during hypoxia and hypercapnia with both placebo and digitalis, digitalis significantly potentiated overall ventilatory responses to hypoxia (+67 +/- 12% before versus +98 +/- 3% after digitalis; mean +/- SEM; P < .01) but did not affect the response to hypercapnia. Sympathetic nerve activity increased by 25 +/- 9% during hypoxia before digitalis and 30 +/- 10% during hypoxia after digitalis (P = NS) and increased by 38 +/- 18% during hypercapnia before digitalis and 26 +/- 11% during hypercapnia after digitalis (P = NS). Digitalis did not significantly change responses to the cold pressor test. Placebo had no effect on ventilatory and sympathetic nerve activity responses. We conclude that digitalis selectively augments ventilatory responses to peripheral chemoreceptor stimulation by hypoxia.
Kinins contribute to the improvement of insulin sensitivity during treatment with angiotensin converting enzyme inhibitor.
Authors: Tomiyama H , Kushiro T , Abeta H , Ishii T , Takahashi A , Furukawa L , Asagami T , Hino T , Saito F , Otsuka Y
Published: June 2012

Although angiotensin converting enzyme inhibitors and alpha 1-blockers have been reported to improve insulin sensitivity, their mechanisms of action have not been elucidated. To investigate the role of kinins in insulin sensitivity, we treated 4-week-old spontaneously hypertensive rats with either an angiotensin converting enzyme inhibitor (enalapril), an alpha 1-blocker (doxazosin), or an angiotensin II antagonist (losartan) for 3 weeks. A control group received no drugs. In addition, 18 rats treated with enalapril or doxazosin received a simultaneous administration of a kinin antagonist (Hoe 140). Glucose clamp testing was performed in each group. Enalapril (128 +/- 1 mmHg) and doxazosin (132 +/- 2 mmHg) decreased mean blood pressure compared with control levels (148 +/- 1 mmHg) (P < .01). The glucose requirement for the clamp test during the administration of enalapril (25.8 +/- 0.5 mg/kg per minute) or doxazosin (28.6 +/- 0.7 mg/kg per minute) was higher than that of the control group (19.8 +/- 0.5 mg/kg per minute) (P < .05). Although Hoe 140 did not alter the glucose requirement of doxazosin (27.8 +/- 0.5 mg/kg per minute), it decreased that of enalapril (22.6 +/- 0.9 mg/kg per minute) (P < .05) without affecting the changes in mean blood pressure induced by enalapril. In addition, losartan decreased mean blood pressure but did not affect the glucose requirement. Thus, the improvement in insulin sensitivity produced by an angiotensin converting enzyme inhibitor is mostly dependent on kinins but not on angiotensin II antagonism, and an alpha 1-blocker improves insulin sensitivity irrespective of kinins.
High-fructose feeding elicits insulin resistance, hyperinsulinism, and hypertension in normal mongrel dogs.
Authors: Martinez F J , Rizza R A , Romero J C
Published: June 2012

To determine whether chronic high-fructose feeding causes insulin resistance and hypertension in normal dogs, we fed 10 male dogs a normosodic diet containing 60% of the calories as fructose for 20 to 28 days; a control group of 8 dogs was fed a similar diet containing dextrose instead of fructose. In the fructose-fed group, (1) fasting triglyceridemia increased from 35.3 +/- 0.63 to 91.9 +/- 11.55 mg/dL after 25 days (P < .001); (2) fasting insulinemia increased from 19.0 +/- 1.9 to 58.9 +/- 7.22 microU/mL after 25 days (P < .001); (3) insulin resistance, which was estimated by steady-state glycemia during an insulin suppression test, increased from 105.8 +/- 21.5 to 187.8 +/- 32.6 mg/dL after 15 days (P < .001), whereas steady-state insulinemia did not change; (4) mean arterial pressure increased from 100.4 +/- 1.6 to 122.6 +/- 2.3 mm Hg after 28 days (P < .01); and (5) cumulative sodium balance was increased on days 7 through 11 (111.60 +/- 4.44 mEq on day 8, P < .01), returning to normal for the rest of the experiment. All these parameters were similar between the fructose-fed and dextrose-fed groups before the diets were started and remained constant in the dextrose-fed group. Neither group showed any change in body weight, fasting plasma glucose, atrial natriuretic factor, or endothelin-1 levels. We conclude that chronic high-fructose feeding elicits hypertriglyceridemia, insulin resistance, hyperinsulinemia, hypertension, and a transient sodium retention in dogs without fostering fasting hyperglycemia or weight gain.(ABSTRACT TRUNCATED AT 250 WORDS)
Baroreflex failure in a patient with central nervous system lesions involving the nucleus tractus solitarii.
Authors: Biaggioni I , Whetsell W O , Jobe J , Nadeau J H
Published: June 2012

Animal studies have shown the importance of the nucleus tractus solitarii, a collection of neurons in the brain stem, in the acute regulation of blood pressure. Impulses arising from the carotid and aortic baroreceptors converge in this center, where the first synapse of the baroreflex is located. Stimulation of the nucleus tractus solitarii provides an inhibitory signal to other brain stem structures, particularly the rostral ventrolateral medulla, resulting in a reduction in sympathetic outflow and a decrease in blood pressure. Conversely, experimental lesions of the nucleus tractus solitarii lead to loss of baroreflex control of blood pressure, sympathetic activation, and severe hypertension in animals. In humans, baroreflex failure due to deafferentation of baroreceptors has been previously reported and is characterized by episodes of severe hypertension and tachycardia. We present a patient with an undetermined process of the central nervous system characterized pathologically by ubiquitous infarctions that were particularly prominent in the nucleus tractus solitarii bilaterally but spared the rostral ventrolateral medulla. Absence of a functioning baroreflex was evidenced by the lack of reflex tachycardia to the hypotensive effects of sodium nitroprusside, exaggerated pressor responses to handgrip and cold pressor test, and exaggerated depressor responses to meals and centrally acting alpha 2-agonists. This clinicopathological correlate suggests that the patient's baroreflex failure can be explained by the unique combination of the destruction of sympathetic inhibitory centers (ie, the nucleus tractus solitarii) and preservation of centers that exert a positive modulation on sympathetic tone (ie, the rostral ventrolateral medulla).
Dietary calcium and blood pressure in experimental models of hypertension. A review.
Authors: Hatton D C , McCarron D A
Published: June 2012

More than 80 studies have reported lowered blood pressure after dietary calcium enrichment in experimental models of hypertension. The evidence presented here suggests that dietary calcium may act concurrently through a number of physiological mechanisms to influence blood pressure. The importance of any given mechanism may vary depending on the experimental model under consideration. Supplemental dietary calcium is associated with reduced membrane permeability, increased Ca(2+)-ATPase and Na,K-ATPase, and reduced intracellular calcium. These results suggest that supplemental calcium may limit calcium influx into the cell and improve the ability of the VSMC to extrude calcium. This could be a direct effect of calcium on the VSMC or an indirect effect mediated hormonally. The calcium-regulating hormones have all been found to have vasoactive properties and therefore may influence blood pressure. Furthermore, CGRP and the proposed parathyroid hypertensive factor are both vasoactive substances that are responsive to dietary calcium. Therefore, diet-induced variations in calcium-regulating hormones may influence blood pressure. Modulation of the sympathetic nervous system is another important way that dietary calcium can influence blood pressure. There is evidence of altered norepinephrine levels in the hypothalamus as a consequence of manipulations of dietary calcium as well as changes in central sympathetic nervous system outflow. Dietary calcium has also been shown to specifically modify alpha 1-adrenergic receptor activity in the periphery. In some experimental models of hypertension, dietary calcium may alter blood pressure by changing the metabolism of other electrolytes. For example, the ability of calcium to prevent sodium chloride-induced elevations in blood pressure may be attributed to natriuresis. However, natriuresis does not account for all of the interactive effects of calcium and sodium chloride on blood pressure. Sodium chloride-induced hypertension may be due in part to calcium wasting and subsequent elevation of calcium-regulating hormones. Chloride is an important mediator of this effect because it appears that sodium does not cause calcium wasting when it is not combined with chloride. More attention to the central nervous system effects of dietary calcium is needed. Not only can calcium itself influence neural function, but many of the calcium-regulating hormones appear to affect the central nervous system. The influence of calcium and calcium-regulating hormones on central nervous system activity may have important implications for blood pressure regulation and also may extend to other aspects of physiology and behavior.
Salt sensitivity in hypertension. Renal and cardiovascular implications.
Authors: Campese V M
Published: June 2012

The mechanisms responsible for the increase in blood pressure response to high salt intake in salt-sensitive patients with essential hypertension are complex and only partially understood. A complex interaction between neuroendocrine factors and the kidney may underlie the propensity for such patients to retain salt and develop salt-dependent hypertension. The possible role of vasodilator and natriuretic agents, such as the prostaglandins, endothelium-derived relaxing factor, atrial natriuretic factor, and kinin-kallikrein system, requires further investigation. An association between salt sensitivity and a greater propensity to develop renal failure has been described in certain groups of hypertensive patients, such as blacks, the elderly, and those with diabetes mellitus. Salt-sensitive patients with essential hypertension manifest a deranged renal hemodynamic adaptation to a high dietary salt intake. During a low salt diet, salt-sensitive and salt-resistant patients have similar mean arterial pressure, glomerular filtration rate, effective renal plasma flow, and filtration fraction. On the other hand, during a high salt intake glomerular filtration rate does not change in either group, and effective renal blood flow increases in salt-resistant but decreases in salt-sensitive patients; filtration fraction and glomerular capillary pressure decrease in salt-resistant but increase in salt-sensitive patients. Salt-sensitive patients are also more likely than salt-resistant patients to manifest left ventricular hypertrophy, microalbuminuria, and metabolic abnormalities that may predispose them to cardiovascular diseases. In conclusion, salt sensitivity in hypertension is associated with substantial renal, hemodynamic, and metabolic abnormalities that may enhance the risk of cardiovascular and renal morbidity.
Human insulin-mediated enhancement of vascular beta-adrenergic responsiveness.
Authors: Gros R , Borkowski K R , Feldman R D
Published: June 2012

Insulin may play an important role in the physiological and/or pathophysiological regulation of the cardiovascular system. Defects in insulin secretion and insulin receptor responsiveness have been associated with increased peripheral resistance and hypertension. The mechanisms linking these events remain unclear. To assess the effect of insulin on beta-adrenergic-mediated vasodilation, we examined aortic ring segments obtained from normotensive male Wistar and spontaneously hypertensive rats. Vessels were maximally preconstricted with phenylephrine (3 mumol/L). Relaxation was induced by either isoproterenol (10 mumol/L) or sodium nitroprusside (10 nmol/L), and the relaxant response was followed for 20 minutes. Insulin exposure did not alter phenylephrine-mediated constriction. However, insulin mediated a dose-dependent increase in isoproterenol-induced relaxation, to a maximum of 120 +/- 4% of baseline isoproterenol-mediated relaxation, with an EC50 for insulin of 32 pmol/L in aortic rings from Wistar rats. Insulin exposure also did not alter nitroprusside-mediated relaxation. In contrast to the results obtained in rings from Wistar rats, insulin did not enhance isoproterenol-mediated responses in rings from spontaneously hypertensive rats. Thus, insulin mediates a selective enhancement of vascular beta-adrenergic responsiveness in aortas from normotensive but not hypertensive animals.
Transforming growth factor-beta 1 gene activation and growth of smooth muscle from hypertensive rats.
Authors: Agrotis A , Saltis J , Bobik A
Published: June 2012

Cultured vascular smooth muscle cells derived from the spontaneously hypertensive rat (SHR) are known to replicate more rapidly than cells from the normotensive Wistar-Kyoto (WKY) rat. In this study we compared the responses of vascular smooth muscle cells from the two strains to transforming growth factor-beta 1 (TGF-beta 1) and evaluated its potential to account for the different growth properties of these cells in response to a number of vascular-derived growth factors. TGF-beta 1 potentiated the proliferative effects of epidermal growth factor, basic fibroblast growth factor, or the different isoforms of platelet-derived growth factor on vascular smooth muscle cells from SHR but inhibited growth factor-stimulated proliferation of vascular smooth muscle cells from WKY rats. These differential effects of TGF-beta 1 on proliferation could not be attributed to alterations in the expression of the type I, II, or III TGF-beta receptors but appeared more related to the ability of cells to autoinduce the TGF-beta 1 gene. TGF-beta 1 caused a time-dependent increase in its own mRNA levels in vascular smooth muscle cells of WKY rats but attenuated levels in vascular smooth muscle cells of SHR. This effect was specific to TGF-beta 1 autoinduction since similar elevations in TGF-beta 1 mRNA levels were observed when vascular smooth muscle cells from the two rat strains were exposed to phorbol myristate acetate, basic fibroblast growth factor, or platelet-derived growth factor-BB.(ABSTRACT TRUNCATED AT 250 WORDS)
Is microalbuminuria a marker of early intrarenal vascular dysfunction in essential hypertension?
Authors: Mimran A , Ribstein J , DuCailar G
Published: June 2012

The relation between basal intrarenal hemodynamics and the renal response to acute inhibition of angiotensin-converting enzyme by captopril and albuminuria was assessed in 106 lean patients with essential hypertension without detectable proteinuria. It was observed that the microalbuminuric group (24.5% of the total population) was characterized by a higher systemic arterial pressure, a lower level of high-density lipoprotein cholesterol, and similar mean values of age, duration of hypertension, glomerular filtration rate, renal plasma flow, filtration fraction, and plasma renin activity when compared with normoalbuminuric subjects. In response to captopril, a significant renal vasodilatation without a change in glomerular filtration rate or a fall in filtration fraction was observed in normoalbuminuric patients only. In contrast, the renal vasodilator response was abolished in microalbuminuric subjects, together with blunting of the rise in plasma renin activity associated with captopril. This occurred despite similar indexes of activity of the endogenous renin-angiotensin system. It is suggested that microalbuminuria may be a marker of early functional or fixed intrarenal vascular dysfunction in never-treated lean patients with essential hypertension.
Rat renal interstitial bradykinin, prostaglandin E2, and cyclic guanosine 3',5'-monophosphate. Effects of altered sodium intake.
Authors: Siragy H M , Ibrahim M M , Jaffa A A , Mayfield R , Margolius H S
Published: June 2012

Kinins generated intrarenally probably affect renal function by altering levels of various mediators and messengers, including prostaglandin E2 (PGE2) and cyclic guanosine 3',5'-monophosphate (cGMP). Using a microdialysis technique, we monitored levels of cortical and medullary renal interstitial fluid kinins, PGE2, and cGMP after 5 days of 0.15% (low), 0.28% (normal), or 4.0% (high) sodium intake. Samples were collected from anesthetized rats (n = 5 for each diet). During normal sodium intake, renal interstitial fluid kinin, PGE2, and cGMP levels in dialysate leaving the cortex were 113 +/- 8 pg/min, 1.23 +/- 0.11 pg/min, and 0.05 +/- 0.004 pmol/min, respectively. In the fluid leaving the medulla, the levels were 93.0 +/- 17 pg/min, 2.28 +/- 0.14 pg/min, and 0.08 +/- 0.005 pmol/min, respectively. In rats consuming a low sodium diet, renal cortical interstitial fluid kinin and cortical and medullary PGE2 and cGMP appearance rates were significantly increased (P < .01). Rats consuming a high sodium diet showed renal cortical and medullary kinin levels that were decreased 100-fold (P < .01), whereas PGE2 and cGMP were increased (P < .01) compared with levels in rats with normal sodium intake. Renal interstitial fluid kinin is extremely sensitive to dietary sodium, but changes in interstitial fluid PGE2 and cGMP are not always directionally similar, suggesting different regulations of these substances in response to sodium intake.
Body mass index and associations of sodium and potassium with blood pressure in INTERSALT.
Authors: Dyer A R , Elliott P , Shipley M , Stamler R , Stamler J
Published: June 2012

This report further examines the relation of body mass index (BMI) to associations of 24-hour urinary sodium, potassium, and sodium-potassium ratio with blood pressure in INTERSALT, a 52-center international study of electrolytes and blood pressure. Analyses without adjustment for BMI indicated average systolic pressure greater by 6.00 mm Hg per 100 mmol higher sodium and diastolic by 2.52 mm Hg. With adjustment for BMI, these values were reduced to 3.14 and 0.14 mm Hg, respectively. For the sodium-potassium ratio, blood pressure associations were stronger when not adjusted for BMI, and for potassium, adjustment generally had little effect. To explore possible interactions of these variables with BMI in relation to blood pressure, the 52 centers were divided into two groups of 26 based on whether the center median for BMI was less than or greater than or equal to 24.5 kg/m2, and individuals within each of the 52 centers were classified into lower- or higher-BMI groups based on individual BMI less than or greater than or equal to 24.1 kg/m2. Sodium and the sodium-potassium ratio were positively and significantly and potassium inversely and significantly related to systolic pressure in all four of these subgroups, and the sodium-potassium ratio and potassium were related to diastolic pressure in two and three subgroups, respectively. Electrolyte-blood pressure associations did not differ significantly between the two subgroups of centers or between the two subgroups based on individuals.(ABSTRACT TRUNCATED AT 250 WORDS)
Genetic contamination of Dahl SS/Jr rats. Impact on studies of salt-sensitive hypertension.
Authors: St Lezin E M , Pravenec M , Wong A , Wang J M , Merriouns T , Newton S , Stec D E , Roman R J , Lau D , Morris R C
Published: June 2012

The Dahl salt-sensitive rat (SS/Jr) is a widely used animal model of salt-sensitive hypertension. SS/Jr rats are believed to be highly inbred and uniformly sensitive to the hypertensinogenic effects of sodium chloride, but we have recently observed that SS/Jr rats from Harlan Sprague Dawley, Inc, exhibit considerable variability in their blood pressure response to supplemental dietary salt. To test the possibility that commercially available SS/Jr rats are genetically contaminated and therefore no longer fully inbred, we performed molecular genetic studies and blood pressure measurements in several groups of SS/Jr rats purchased from Harlan Sprague Dawley. We found molecular evidence of heterozygosity and/or atypical allelic variants involving loci on at least five different chromosomes. Many of the rats also failed to exhibit a salt-sensitive blood pressure phenotype. We conclude that SS/Jr rats being sold by the only commercial vendor of Dahl rats in the United States are genetically contaminated and resistant to the hypertensinogenic effects of salt. These findings raise serious questions about the interpretation of research conducted with SS/Jr rats obtained from Harlan Sprague Dawley.
Structural remodeling in hypertensive heart disease and the role of hormones.
Authors: Weber K T , Sun Y , Guarda E
Published: June 2012

In hypertension, the risk of adverse cardiovascular events, including heart failure, is increased in the presence of left ventricular hypertrophy. Morphological studies suggest that it is not the quantity but rather the quality, or structure, of myocardium that confers such risk. Iterations in tissue structure that appear in hypertensive heart disease include a remodeling of intramyocardial coronary arterioles, similar to that found in systemic organs, and a disproportionate accumulation of fibrillar collagen within their adventitia and neighboring interstitial space. Microscopic scars replacing necrotic cardiac myocytes are also evident. These expressions of fibrosis appear in the normotensive, nonhypertrophied right and hypertensive, hypertrophied left ventricles and are linked to the renin-angiotensin-aldosterone system. Cardiac myocyte growth, the major determinant of myocardial mass, is related to ventricular loading. Mechanisms responsible for the reactive and reparative fibrosis with renin-angiotensin-aldosterone system activation are under investigation. In vitro quantitative autoradiography has identified angiotensin II, aldosterone, endothelin, and bradykinin receptors in the myocardium. A nonendothelial tissue angiotensin-converting enzyme, whose binding density is marked in the matrix of heart valves, adventitia, and sites of fibrosis, irrespective of its pathogenic basis, has also been found. This angiotensin-converting enzyme may be responsible for regulating local concentrations of angiotensin II and bradykinin that govern fibroblast collagen turnover. Based on a paradigm of discordant reciprocal regulation, in which a relative abundance of stimulators (eg, angiotensin II, aldosterone, and endothelins) of collagen synthesis exceeds inhibitors (eg, bradykinin, prostaglandins, and glucocorticoids), fibrous tissue appears.(ABSTRACT TRUNCATED AT 250 WORDS)
Microalbuminuria in 411 untreated individuals with established hypertension, white coat hypertension, and normotension.
Authors: Høegholm A , Bang L E , Kristensen K S , Nielsen J W , Holm J
Published: June 2012

We compared urinary albumin excretion in normotensive subjects and patients with white coat and established hypertension. The study involved prospective comparison of office blood pressure, daytime ambulatory blood pressure, and urinary albumin excretion in consecutive patients (n = 284) who were selected from general practice with newly diagnosed mild to moderate hypertension before the institution of pharmacologic antihypertensive therapy. All patients had a diastolic office blood pressure above 90 mm Hg; 173 had a consistently elevated diastolic blood pressure (established hypertension), and 111 had an average daytime ambulatory blood pressure below 90 mm Hg (white coat hypertension). A sample of 127 subjects drawn from the Danish national register served as a normotensive control group. The main outcome measure was the ratio of early morning urinary albumin to creatinine. This ratio differed significantly among the three groups, being (on a molar basis) 21 +/- 69 x 10(-6) in the normotensive subjects, 22 +/- 39 x 10(-6) in the white coat hypertensive patients, and 51 +/- 177 x 10(-6) in patients with established hypertension. The difference remained significant after correction for covariables. The ratio of early morning urinary albumin to creatinine was weakly but significantly correlated to blood pressure, was more pronounced for ambulatory than for office measurements, was more pronounced for systolic than for diastolic pressure, and was more pronounced for hypertensive than for normotensive individuals. The ratio was as reproducible a measure as 24-hour albumin excretion. We conclude that white coat hypertensive patients have less renal involvement than patients with established hypertension but more than a normotensive control group.
Increased cardiac types I and III collagen mRNAs in aldosterone-salt hypertension.
Authors: Robert V , Van Thiem N , Cheav S L , Mouas C , Swynghedauw B , Delcayre C
Published: June 2012

Cardiac fibrosis is one of the deleterious events accompanying hypertension that may be implicated in the progression toward heart failure. To determine the mechanisms involved in fibrosis and the role of hemodynamic versus humoral factors, we studied the expression of genes involved in hypertrophy and fibrosis in the heart of rats treated with aldosterone for 2 months with addition of 1% NaCl and 0.3% KCl in water. This treatment induced arterial hypertension, a moderate left ventricular hypertrophy, and a decrease in plasma thyroxine. Equatorial sections of hearts from treated rats showed numerous foci of proliferating nonmuscular cells and a biventricular fibrosis. Computerized videodensitometry demonstrated an increase of collagen volume fraction by 152% and 146% and of the ratio of the perivascular collagen area and vascular area by 86% and 167% in left and right ventricles, respectively. As measured by slot blot, this cardiac fibrosis was accompanied by an increase in alpha 1-I procollagen mRNA by 75% and 160% (P < .01) and in alpha 1-III mRNA by 76% and 319% (P < .01) in left and right ventricles, respectively. Atrial natriuretic peptide mRNA was induced only in the hypertrophied left ventricle. We conclude that fibrosis is occurring and involves pretranslational regulation of collagen synthesis. Whereas hypertrophy and atrial natriuretic peptide mRNA increase are restricted to the left ventricle, fibrosis is initiated in both ventricles, supporting the hypothesis that this cardiac response is independent of hemodynamic factors.
Exercise blood pressure predicts cardiovascular mortality in middle-aged men.
Authors: Mundal R , Kjeldsen S E , Sandvik L , Erikssen G , Thaulow E , Erikssen J
Published: June 2012

The outcome of 1999 apparently healthy men aged 40 to 59 years investigated from 1972 through 1975 was ascertained after 16 years to determine whether systolic blood pressure measured with subjects in the sitting position during a bicycle ergometer exercise test adds prognostic information on cardiovascular mortality beyond that of casual blood pressure measured after 5 minutes of supine rest. During a total follow-up of 31,984 patient years, 278 patients died, 150 from cardiovascular causes. Casual blood pressure and pulse pressure as well as peak exercise systolic blood pressure during 6 minutes on the starting workload of 600 kpm/min (approximately 100 W, 5880 J/min) were all related to cardiovascular mortality. The relative risk (RR) of dying from cardiovascular causes associated with an increment of 48.5 mmHg (= 2 SD) in systolic blood pressure at 600 kilopondmeter (kpm)/min was significant (RR = 1.5, 95% confidence interval [CI] = 1.1-2.3, P = .040) even when adjusting for a large number of variables measured in the present study, including age, exercise capacity, smoking habits, and casual blood pressures. The influence of blood pressure at 600 kpm/min was so strong that the predictive value of resting casual blood pressures became nonsignificant when these were analyzed as continuous variables also including exercise blood pressure as a covariate. However, the maximal systolic blood pressure during the exercise test was unrelated to cardiovascular mortality.(ABSTRACT TRUNCATED AT 250 WORDS)
Adaptation, allometry, and hypertension.
Authors: Weder A B , Schork N J
Published: June 2012

Essential hypertension is a "disease of civilization" but has a clear genetic component. From an evolutionary perspective, persistence in the human genome of elements capable of raising blood pressure presupposes their adaptive significance. Recently, two hypotheses that explicitly appeal to selectionist arguments, the "slavery" and "thrifty gene" theories, have been forwarded. We find neither completely successful, and we advance an alternative explanation of the adaptive importance of genes responsible for hypertension. We propose that blood pressure rises during childhood and adolescence to subserve homeostatic needs of the organism. Specifically, we contend that blood pressure is a flexible element in the repertoire of renal homeostatic mechanisms serving to match renal function to growth. The effect of modern diet and lifestyle on human growth stimulates earlier and more vigorous development, straining biologically necessary relationships between renal and general somatic growth and requiring compensation via homeostatic mechanisms preserved during evolution. Prime among such mechanisms is blood pressure, which rises as a compensation to maintain renal function in the face of greater growth. Since virtually all members of acculturated societies share in the modern lifestyle, the demands imposed by accelerated growth and development result in a populational shift to higher blood pressures, with a consequent increase in the prevalence of hypertension. We propose that hypertension is the product of maladaptation of highly genetically conserved mechanisms subserving important biological homeostatic needs. Elucidation of the mechanisms underlying hypertension will require approaches that examine the developmental processes linking growth to blood pressure.
Effects of pioglitazone on calcium channels in vascular smooth muscle.
Authors: Zhang F , Sowers J R , Ram J L , Standley P R , Peuler J D
Published: June 2012

Pioglitazone, an insulin-sensitizing, antidiabetic agent, has blood pressure-lowering effects in insulin-resistant hypertensive rats and attenuates growth factor-induced increases of intracellular Ca2+ in rat aortic vascular smooth muscle cells. To determine whether modulation of voltage-dependent Ca2+ channels plays a role in this association, we investigated the effects of pioglitazone on voltage-dependent current in cultured rat aortic (a7r5) and freshly dissociated rat tail artery vascular smooth muscle cells. Both cell types were studied with whole-cell patch-clamp techniques. Current through L-type Ca2+ channels was elicited with a voltage ramp in the presence of Ba2+ substituted for Ca2+. T-type Ca2+ current was studied using a two-pulse protocol that enabled the isolation of transient current. In a7r5 vascular smooth muscle cells, 2-minute application of pioglitazone (5 and 10 mumol/L) reduced L-type current by 7.9 +/- 1.0% (n = 8) (mean +/- SEM, number of cells) and 14.5 +/- 3.0% (n = 9) (P < .01, two-tailed paired t test), respectively. In contrast, 2-minute application of pioglitazone had no significant effect on T-type Ca2+ current. In freshly dissociated tail artery vascular smooth muscle cells, 2-minute application of 10 mumol/L pioglitazone had an insignificant effect (4.8 +/- 5.6% reduction); however, 25 mumol/L pioglitazone reduced L-type current by 27.3 +/- 7.2% (n = 5) (P < .01). Two-minute application of 0.1% or 0.2% dimethyl sulfoxide (vehicle) alone had no significant effects on currents in either type of vascular smooth muscle cell.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of a nonselective endothelin antagonist on vascular remodeling in deoxycorticosterone acetate-salt hypertensive rats. Evidence for a role of endothelin in vascular hypertrophy.
Authors: Li J S , Larivière R , Schiffrin E L
Published: June 2012

We have previously shown that the endothelin content in arteries of deoxycorticosterone acetate (DOCA)-salt hypertensive rats is increased. We designed this study to examine, using the new orally active nonselective endothelin receptor antagonist bosentan, whether this increase in vascular endothelin may contribute to elevated blood pressure and vascular hypertrophy in DOCA-salt hypertensive rats. Rats received bosentan (100 mg/kg body wt per day) for 3 weeks mixed with their food. Systolic blood pressure of DOCA-salt hypertensive rats rose to 197 +/- 5 mm Hg, and that of bosentan-treated DOCA-salt hypertensive rats was 177 +/- 4 mm Hg (P < .01). Mesenteric resistance arteries were studied on a wire myograph. The media width, ratio of media width to lumen diameter, and cross-sectional area of the media of resistance arteries of bosentan-treated DOCA-salt hypertensive rats were significantly smaller than those of untreated DOCA-salt hypertensive rats. The lumen diameter and cross-sectional area of the media of vessels of bosentan-treated rats were not different from those of uninephrectomized control rats. Vasoconstrictor responses, which were altered in DOCA-salt hypertensive rats, approached control in the bosentan-treated rats. We conclude that these results with a nonselective endothelin receptor antagonist may suggest a role for endothelin in the elevation of blood pressure and vascular hypertrophy and remodeling in DOCA-salt hypertensive rats.