bluuebunny/crossref_metadata_2025 huggingface dataset:
Renal and systemic hemodynamics in sustained essential hypertension.
Authors: London G M , Safar M E , Sassard J E , Levenson J A , Simon A C
Published: June 2012

Cardiac output (CO), renal blood flow (RBF), calf blood flow (CBF), and hepatic blood flow (HBF), glomerular filtration rate (GFR), and dopamine beta hydroxylase (D beta H) activity were studied in 198 men (67 normotensive controls and 131 hypertensive patients) of the same age with sustained uncomplicated essential hypertension. In the hypertensive men, the RBF and the RBF/CO ratio were significantly decreased (p less than 0.001). The RBF and RBF/CO ratio were negatively correlated with age (p less than 0.01), blood pressure (p less than 0.01), and D beta H activity (p less than 0.01). None of these relationships were observed with CBF and HBF. The observed decreases in RBF and the RBF/CO ratio in hypertensive men were reversed after administration of clonidine and alpha-methyldopa (p less than 0.01), but not after administration of propranolol. The study provides evidence that the reduction of renal perfusion in essential hypertension is partly reversible and related to an abnormality in the adrenergic system control.
Left ventricular mass reduction during salt depletion in arterial hypertension.
Authors: Ferrara L A , de Simone G , Pasanisi F , Mancini M , Mancini M
Published: June 2012

Long-term therapy with antihypertensive agents that reduce sympathetic nervous system activity has been demonstrated by echocardiographic measurements to reverse left ventricular hypertrophy. This investigation evaluated the effects of salt depletion obtained by both chlorthalidone (25 mg/day) and severe restriction of salt intake (about 1016 mg Na+/day) on left ventricular mass (LVM) in as short a time as 12 weeks. Before the study, the patients had been off medication and on a balanced diet without salt restriction for at least 2 weeks; they were then randomly allocated to either the diuretic or low-salt regimen for 6 weeks and finally to alternative treatment according to a crossover model. Blood pressure, body weight, myocardial mass, and noninvasive measurements of left ventricular function (LVF) were determined at baseline and at the end of both periods of treatment. Results were evaluated by two-way analysis of variance in randomized blocks. Systolic and diastolic blood pressure and LVM were significantly and similarly reduced by diuretic therapy or salt restriction. A significant correlation was demonstrated between noninvasive measurements of LVM, expressed as cross-sectional area, and systolic blood pressure. No impairment of LVF could be detected over the treatment period.
Partial deficiency of adrenal 11-hydroxylase. A possible cause of primary hypertension.
Authors: de Simone G , Tommaselli A P , Rossi R , Valentino R , Lauria R , Scopacasa F , Lombardi G
Published: June 2012

Results of supraphysiological adrenocorticotropic hormone (ACTH) stimulation of biosynthetic pathways of adrenal zona fasciculata indicate that a deficiency of 11-hydroxylase exists in patients with essential hypertension. The deficiency is suggested by the much greater stimulus of synthesis of deoxycorticosterone (DOC) and deoxycortisol in hypertensive subjects than in controls (p less than 0.001). No significant difference in the synthesis of cortisol, corticosterone, progesterone, 17-hydroxyprogesterone (17-OHP), and delta-4-androstenedione (D4) was observed between the two groups. The ratios for synthesis of DOC and corticosterone and for deoxycortisol and cortisol found in hypertensive patients were significantly higher than those found in controls (p less than 0.001); no significant difference was observed in the synthesis of 17-OHP and progesterone. The synthesis of DOC and deoxycortisol was not significantly correlated with either blood pressure or plasma renin activity. Plasma renin activity was significantly lower in hypertensive subjects than in normotensive subjects (p less than 0.0001), while no difference was found in aldosterone secretion between the two groups. The 11-hydroxylase deficiency in the adrenal zona fasciculata may be one of the genetic factors causing hypertension together with environmental factors (particularly salt intake and work-related stress). The investigation performed in our study may be useful for the evaluation of adrenal zona fasciculata enzymatic activities during the study of hypertensive patients.
The contribution of vasopressin and angiotensin to the maintenance of blood pressure after autonomic blockade.
Authors: Hiwatari M , Nolan P L , Johnston C I
Published: June 2012

The contribution of vasopressin and angiotensin II to the maintenance of blood pressure after short-term autonomic blockade was investigated in conscious Long-Evans and Brattleboro (vasopressin-deficient; hereditary diabetes insipidus) rats. After short-term autonomic blockade by atropine (1 mg/kg), propranolol (5 mg/kg), and pentolinium (5 mg/kg and 10 mg/kg/hr), the fall in blood pressure was significantly greater in Brattleboro rats than in Long-Evans rats (48 +/- 3 vs 32 +/- 2 mm Hg; p less than 0.01). Administration of the vasopressin vascular receptor antagonist D(CH2)5Tyr-(Me)AVP (2 micrograms/kg) caused further blood pressure decreases only in Long-Evans rats, so that the final blood pressure in both groups was identical. Administration of enalaprilat (10 mg/kg), an angiotensin converting enzyme inhibitor, further reduced blood pressure in both strains. When enalaprilat was given first after autonomic blockade, it reduced blood pressure in Brattleboro rats but not in Long-Evans rats. Administration of the vasopressin antagonist after enalaprilat further reduced blood pressure only in Long-Evans rats. The fall in blood pressure following vasopressin blockade was greater than that occurring after angiotensin converting enzyme inhibition (14 +/- 1 vs 6 +/- 1 mm Hg; p less than 0.05) in autonomic blockade Long-Evans rats. Plasma levels of vasopressin in Long-Evans rats increased markedly after short-term autonomic blockade, whereas plasma renin and angiotensin II levels were unchanged. Plasma angiotensin II levels were increased by the vasopressin antagonist and decreased by enalaprilat. We conclude that, due to sympathetic nervous system blockade and consequent blunting of renal renin release, vasopressin has a greater capacity than the renin-angiotensin system for maintaining blood pressure after short-term autonomic blockade.
Lack of alerting reactions to intermittent cuff inflations during noninvasive blood pressure monitoring.
Authors: Parati G , Pomidossi G , Casadei R , Mancia G
Published: June 2012

Intermittent noninvasive blood pressure monitoring is becoming increasingly popular because of the belief that a daytime blood pressure profile can provide a better clinical evaluation of hypertension than that provided by casual blood pressure measurements. This approach has potential limitations, however, one of which is that the cuff inflations permitting blood pressure to be repeatedly measured may induce an alerting reaction and a pressor response in the patients and lead to an overestimation of their daytime blood pressure. Blood pressure in 22 subjects was invasively recorded for 24 hours by the Oxford method. During the day of the recording blood pressure was also measured by a noninvasive device (Vita-Stat 901), which had its cuff applied to the opposite arm from which the intra-arterial signal was derived. For 2 hours the device provided automatic cuff inflations at 10-minutes intervals. For another 2 hours it was programmed to provide cuff inflations only following patients' commands, also at 10-minute intervals. Analysis of the intra-arterial blood pressure trace during the periods preceding and following the automatically or semiautomatically induced cuff inflations showed that these procedures caused no increment in systolic and diastolic blood pressure. This finding applied not only to the mean data but also to each individual measurement considered separately, including the initial one. Our results indicate that automatic and semiautomatic blood pressure monitorings do not induce an alarm reaction and a blood pressure rise and thus do not overestimate daytime blood pressure values.
Evidence of early degenerative changes in large arteries in human essential hypertension.
Authors: Simon A C , Levenson J , Bouthier J , Safar M E , Avolio A P
Published: June 2012

Noninvasive evaluation of brachial artery diameter (pulsed Doppler velocimetry) and pulse wave velocity (strain gauge mechanography) was performed in 23 normal subjects and 49 patients with uncomplicated essential hypertension. Pulsatile arterial function was described in terms of derived characteristic impedance and arterial compliance. Compared with normal controls, hypertensive patients had greater arterial diameter (p less than 0.01) and pulse wave velocity (p less than 0.001). Two nomograms obtained from normal subjects relating the product of age and diastolic pressure to diameter and pulse wave velocity were used for analysis of the hypertensive group; 35 patients were inside the 95% confidence limits of the diameter and pulse wave velocity nomograms (Group 1), while 14 patients were outside the pulse wave velocity nomogram (Group 2). Age and mean pressure were similar, but pulse wave velocity was higher (p less than 0.001), arterial compliance lower (p less than 0.001), and characteristic impedance higher (p less than 0.001) in Group 2 than in Group 1. The amplitude of pulse pressure was higher in Group 2 than in Group 1 (p less than 0.001), and a negative correlation was found between pulse pressure and arterial compliance in Group 2, but not in Group 1. Thus, in the majority of hypertensive patients, arterial modifications could be related to the normal influence of age and pressure. In contrast, other patients exhibited features suggesting excessive arterial stiffness, manifested by abnormally high pulse wave velocity, decreased arterial compliance, and increased characteristic impedance.
Evidence for a direct effect of alcohol consumption on blood pressure in normotensive men. A randomized controlled trial.
Authors: Puddey I B , Beilin L J , Vandongen R , Rouse I L , Rogers P
Published: June 2012

A direct pressor effect of alcohol is proposed as the basis for the association between regular alcohol consumption and an increase in blood pressure found in population studies. To examine this further, a randomized controlled crossover trial of the effects of varying alcohol intake on blood pressure in 46 healthy male drinkers was conducted. From an average of 336 ml of ethanol per week, alcohol consumption was reduced by 80% for 6 weeks by drinking a low alcohol content beer alone. This reduction was associated with a significant reduction in systolic and diastolic blood pressure (p less than 0.001 and p less than 0.05 respectively). The mean difference in supine systolic blood pressure during the last 2 weeks of normal or low alcohol intake was 3.8 mm Hg, which correlated significantly with change in alcohol consumption (r = 0.53, p less than 0.001). Reduction of alcohol intake also caused a significant decrease in weight (p less than 0.001). After adjustment for weight change, an independent effect of alcohol on systolic but not diastolic blood pressure was still evident, with a 3.1 mm Hg fall predicted for a decrease in consumption from 350 ml of ethanol equivalent per week to 70 ml per week (p less than 0.01). Systolic blood pressure rose again when normal drinking habits were resumed. These results provide clear evidence for a direct and reversible pressor effect of regular moderate alcohol consumption in normotensive men and suggest that alcohol may play a major role in the genesis of early stages of blood pressure elevation.
Autoregulation of tissue blood flow in essential hypertension.
Authors: Blake S , Carey M , McShane A , Walley T
Published: June 2012

Autoregulation of tissue blood flow is a mechanism by which tissues control their own blood supply. The mechanism is dependent on an intrinsic capacity of tissues to vary their arteriolar resistance in relation to their needs. One view of the nature of the increased peripheral resistance in essential hypertension is that it represents autoregulatory vasoconstriction functioning to hold in check a cardiac output that would otherwise be excessive; in this situation autoregulation would be functioning normally. An alternative view is that the increased peripheral resistance represents the effect of a direct-acting vasoconstrictor substance; in this situation autoregulation would be rendered defective in its vasodilator capacity. A study of autoregulatory vasodilatation in eight subjects with essential hypertension supported an autoregulatory mechanism as the cause of the increased peripheral resistance.
Effect of dietary chloride on salt-sensitive and renin-dependent hypertension.
Authors: Whitescarver S A , Holtzclaw B J , Downs J H , Ott C E , Sowers J R , Kotchen T A
Published: June 2012

We have previously reported that 1) selective dietary sodium loading (without chloride) does not produce hypertension in rats of the Dahl salt-sensitive strain (DS) and 2) selective chloride loading (without sodium) lowers plasma renin activity in the intact Sprague-Dawley rat maintained on a low NaCl diet. The present study examined the effect of selective dietary chloride loading on two models of hypertension: the DS and the renin-dependent one-kidney, one clip Sprague-Dawley rat. The DS were pair-fed (n = 7/group) a "normal" NaCl, a high NaCl (4%), or a "normal" sodium-high chloride diet for 11 weeks. From Week 7 until the end of the experiment, the high NaCl-fed animals had higher (p less than or equal to 0.05) blood pressures than animals fed either the normal NaCl or normal sodium-high chloride diet, which were not different from each other. Thus, in the DS, hypertension depends on high dietary intakes of both sodium and chloride. In one-kidney, one clip hypertensive rats, selective chloride loading failed to lower plasma renin activity (9 +/- 1 vs 7 +/- 1 ng angiotensin I/ml/hr) or to prevent hypertension (160 +/- 10 vs 166 +/- 9 mm Hg). Thus, selective dietary chloride loading (without sodium) does not alter blood pressure in either salt-sensitive or renin-dependent hypertension.
How does salt raise blood pressure? A hypothesis.
Authors: Gavras H
Published: June 2012

Existing data in the literature indicate that alpha 2-adrenergic receptor agonists have a profound hypotensive action, that sodium attenuates the affinity of alpha 2-adrenergic receptors for agonists, that the location of these receptors in the central nervous system is mainly at the sites of cardiovascular regulation, and that these sites exert a constant tonic inhibition of sympathetic vasoconstrictor tone. This article proposes the theory that sodium exerts its hypertensive action by decreasing the state of affinity of the alpha 2-adrenergic receptors of the central nervous system for locally occurring agonist neurotransmitters, which results in disinhibition of sympathoinhibitory neurons and leads to the hyperadrenergic state characteristic of salt-induced hypertension.
Factors related to blood pressure in a biracial adolescent female population.
Authors: Liebman M , Chopin L F , Carter E , Clark A J , Disney G W , Hegsted M , Kenney M A , Kirmani Z A , Koonce K L , Korslund M K
Published: June 2012

Blood pressure levels, anthropometric parameters, and dietary intakes were assessed in 1981 and 1983 in a population of black (n = 236) and white (n = 296) adolescent girls, aged 14 and 16 years in 1983. The 14-year-old black girls exhibited significantly higher mean systolic and diastolic blood pressures than whites in both years. Body weight and Quetelet index were more strongly associated with blood pressure than were height and triceps skinfold thickness. Correcting blood pressures for weight, Quetelet index, 2-year changes in height, and age at menarche decreased in each case (but did not negate) the observed race differences in blood pressure. Dietary calcium and potassium intakes were inversely related to blood pressure, and a race difference in the intake of these nutrients (whites greater than blacks) was observed. Covariate adjustment for calcium, but not for potassium, decreased the magnitude of race differences in blood pressure. Family type (single-parent vs nuclear) and place of residence (urban vs nonurban) appeared to be the most important confounding variables for race differences in blood pressure, since differences largely were eliminated by controlling for these factors. Conflicting reports in the literature regarding the age range during which race differences in blood pressure become apparent may be partially attributed to the complex interrelationships among these factors and the potential influence of other genetic-environmental interactions that may also play a role in blood pressure regulation.
Vasodepressor role of endogenous bradykinin assessed by a bradykinin antagonist.
Authors: Benetos A , Gavras H , Stewart J M , Vavrek R J , Hatinoglou S , Gavras I
Published: June 2012

This study was designed to examine the contribution of bradykinin to the depressor effect of different antihypertensive drugs in two-kidney renovascular hypertensive rats, using a new specific antagonist of bradykinin. First, the inhibitory capacity of this peptide for exogenously injected bradykinin (75-200 ng) was tested. An inhibition of the vasodepressor action of bradykinin by over 50% was found when the bradykinin inhibitor was infused at a rate of 40 micrograms/min, with little difference at higher rates of infusion. This inhibitor then was infused in three groups of renovascular hypertensive rats after their blood pressure had been decreased by pretreatment with the converting enzyme inhibitor enalapril (MK 421), saralasin, or sodium nitroprusside, respectively. Infusion of the inhibitor produced an immediate 30% increase in blood pressure only in the enalapril-treated group. These results indicate that bradykinin is involved in the decrease of blood pressure produced by converting enzyme inhibition in experimental renovascular hypertension.
Experimental hypertension in young and adult animals.
Authors: Zicha J , Kunes J , Jelínek J
Published: June 2012

The susceptibility of immature and adult animals to various environmental factors often differs because the response of the young organism can only involve those regulatory mechanisms that are available at the particular stage of development. Increased sensitivity to certain (e.g., hypertensive) stimuli may be limited to a relatively short age period that is usually characterized by the maturation of some important physiological functions. High salt intake seems to influence the animals especially during the weaning period and prepuberty, in the course of which profound developmental changes of circulation, electrolyte metabolism, and neurohumoral regulation have been demonstrated. Indeed, salt-dependent forms of experimental hypertension are more severe when they are induced in immature animals. Moreover, substantial differences in hemodynamics, distribution of body fluids, and involvement of pressor and natriuretic agents indicate that the mechanisms of salt hypertension need not be the same in immature and adult animals. For this reason, increased attention should be paid to developmental factors in the study of induced forms of experimental hypertension.
Thromboxane synthesis and blood pressure in spontaneously hypertensive rats.
Authors: Purkerson M L , Martin K J , Yates J , Kissane J M , Klahr S
Published: June 2012

The present study examines effects of administration of OKY 046, an inhibitor of thromboxane synthesis, for 100 days on systemic blood pressure and renal function in spontaneously hypertensive rats and in normotensive control rats. Untreated spontaneously hypertensive rats had higher values for thromboxane excretion in the urine and higher values for blood pressure than did normotensive control rats. Administration of OKY 046 decreased systolic and mean arterial blood pressure and urinary excretion of thromboxane and protein in spontaneously hypertensive rats. Administration of OKY 046 decreased thromboxane excretion in the urine of normotensive control rats but had no effect on blood pressure or protein excretion. Renal function, as assessed by the clearances of inulin and p-aminohippuric acid, was greater in spontaneously hypertensive rats treated with OKY 046 than in those receiving vehicle alone. In normotensive control rats, OKY 046 administration did not affect renal function. These results suggest that increased renal synthesis of thromboxane may play a role in the pathogenesis of the elevated blood pressure of spontaneously hypertensive rats.
Hypertensive potency of 18-oxocortisol in the rat.
Authors: Hall C E , Gomez-Sanchez C E
Published: June 2012

The hypertensogenic effect of 18-oxocortisol, an aldosterone analogue possessing both mineralocorticoid and glucocorticoid properties, was studied at the same dosage but under different experimental conditions in two experiments. Under experimental conditions conducive to the development of mineralocorticoid hypertension (i.e., rats with a single kidney on a high NaCl intake), there was an extremely rapid onset of saline polydipsia and hypertension accompanied by cardiac and renal enlargement, marked thymic involution without adrenal atrophy, cardiovascular lesions, and hypokalemia. With the exception of the thymic changes, the same changes occurred in rats given the biologically equivalent dose of deoxycorticosterone acetate. Under circumstances favoring the development of glucocorticoid hypertension (i.e., intact rats on a normal sodium intake), the same dose had only a transient blood pressure-elevating effect, attaining prehypertensive levels at most, and caused neither chronic hypertension nor hypokalemia. The biologically equivalent glucocorticoid dosage of cortisol was similarly ineffective. Under these circumstances, both steroids caused thymus involution but only 18-oxocortisol caused kidney enlargement.
Endothelium-dependent contractions to acetylcholine in the aorta of the spontaneously hypertensive rat.
Authors: Lüscher T F , Vanhoutte P M
Published: June 2012

To study the mechanism of decreased endothelium-dependent relaxations in spontaneously hypertensive rats (SHR), rings of thoracic aorta with and without endothelium were taken from age-matched male SHR and normotensive Wistar-Kyoto rats (WKY) and suspended for isometric tension recording. Acetylcholine caused endothelium-dependent contractions in quiescent rings from SHR but not in those from WKY. These contractions were inhibited by atropine but not by hexamethonium and were prevented by inhibitors of phospholipase A2 or cyclooxygenase but not by inhibitors of prostacyclin synthetase, thromboxane synthetase, or leukotriene synthetase. Prostaglandin D2, E1, E2, and F2 alpha caused concentration-dependent contractions in rings without endothelium from both SHR and WKY; the responses to the highest concentration (10(-5) M) of the individual prostaglandins were comparable in both strains. Endothelium-dependent relaxations evoked by high but not by low concentrations of acetylcholine were significantly depressed in SHR as compared with those in WKY (p less than 0.05). Indomethacin normalized endothelium-dependent relaxations in SHR. Thus, acetylcholine can activate muscarinic receptors that evoke endothelium-dependent contractions in the aorta of SHR but not in that of WKY. The contraction probably is mediated by a cyclooxygenase product(s) other than prostacyclin or thromboxane A2. The reduced endothelium-dependent relaxations to acetylcholine in the SHR probably are not due to a decreased release of endothelium-derived relaxing factor(s) but to the simultaneous release of endothelium-derived contracting substance(s).
Evidence for increased levels of a circulating ouabainlike factor in essential hypertension.
Authors: Sagnella G A , Jones J C , Shore A C , Markandu N D , MacGregor G A
Published: June 2012

The effect of plasma from normotensive and hypertensive subjects on the binding of [3H]ouabain on human erythrocytes was investigated. The binding of [3H]ouabain on human erythrocytes was saturable and highly specific; linear Scatchard plots indicated the presence of a single type of binding site. Human plasma decreased the binding of [3H]ouabain on its receptor to a greater extent than could be accounted for by the plasma potassium concentration. The level of this circulating ouabainlike factor (or factors) was quantitated using a radioreceptor assay. Plasma from 22 hypertensive subjects (systolic blood pressure greater than 160 mm Hg or diastolic blood pressure greater than 90 mm Hg) displayed higher levels than that from 24 normotensive subjects; furthermore there was a positive and significant correlation (r = 0.42, n = 46, p less than 0.004) between the ouabainlike content and the individual subject's systolic blood pressure. The receptor assay described is relatively simple and should be useful for further work on the nature and clinical importance of the endogenous ouabainlike factor.
The effect of age and sodium depletion on cardiovascular response to orthostasis.
Authors: Shannon R P , Wei J Y , Rosa R M , Epstein F H , Rowe J W
Published: June 2012

To test the hypothesis that normal age-related limitations in cardiovascular homeostasis may become clinically significant under stress, the cardiovascular response to postural change was assessed in six young and six old healthy subjects before and after modest diuretic-induced sodium depletion. Before diuresis, systolic blood pressure was maintained (from 110 +/- 4 to 113 +/- 6 mm Hg) while heart rate increased 22% (from 67 +/- 2 to 82 +/- 5 beats/min) at 3 minutes after 60-degree upright tilt in young subjects. After a significant diuretic-induced weight reduction and natriuresis, the young again maintained systolic blood pressure (from 110 +/- 4 to 110 +/- 6 mm Hg) and increased heart rate 49% (from 68 +/- 2 to 101 +/- 5 beats/min; p less than 0.05, compared with prediuresis values) in response to the same postural stimulus. During the prediuresis tilt, the older subjects showed no change in systolic blood pressure (from 132 +/- 4 to 134 +/- 6 mm Hg) and a 9% increase in heart rate (from 68 +/- 3 to 74 +/- 2 beats/min). After a similar significant weight reduction and sodium loss, the older subjects showed a significant reduction in systolic blood pressure (from 132 +/- 6 to 108 +/- 6 mm Hg; p less than 0.05) and a 17% increase in heart rate (from 69 +/- 4 to 81 +/- 3 beats/min; p less than 0.05) during tilt compared with values in young subjects. Three of six elderly subjects noted postural symptoms. These results suggest that, although the healthy old may appear well compensated under optimal conditions, decreased cardiovascular reserve renders them susceptible to postural change following mild sodium depletion.
Up-regulation of renal prostaglandin receptors in genetic salt-dependent hypertension.
Authors: Limas C , Limas C J
Published: June 2012

Development of hypertension in Dahl salt-sensitive rats (DS) is accompanied by reduced renomedullary prostaglandin synthesis, which may be responsible for their lower natriuretic capacity. To examine the changes in renomedullary prostaglandin E2 synthesis, the effects of high (8.0%) and normal (0.6%) NaCl diets were examined in DS and in Dahl salt-resistant rats (DR). In response to an 8.0% NaCl diet, the number of prostaglandin E2 receptors in the renal outer medulla of DR increased (2.97 +/- 0.2 vs 2.18 +/- 0.2 pmol/mg on 0.6% NaCl diet) while no change was noted in their affinities (Kd, 9.5 +/- 0.2 vs 9.4 +/- 0.3 nM). Receptor number and affinity in the renal cortex, inner medulla, and liver of DR were not affected. In contrast, renomedullary receptors of DS had a lower affinity than those of age-matched DR (Kd, 13.9 +/- 0.2 nM on 0.6% NaCl diet and 14.0 +/- 0.3 nM on 8.0% NaCl diet) and did not increase in number after a high salt diet. This apparent inability of DS to modulate prostaglandin receptors may contribute to their susceptibility to salt-induced hypertension.
Synthetic atrial natriuretic factor does not dilate resistance-sized arteries.
Authors: Osol G , Halpern W , Tesfamariam B , Nakayama K , Weinberg D
Published: June 2012

The effects of synthetic atrial natriuretic factor and atriopeptin III on induced tone in resistance-sized arteries from the rat were examined in vitro. Cylindrical segments of small mesenteric or cerebral arteries were mounted on a microcannula and pressurized to a transmural pressure of 75 mm Hg. After equilibration, the level of tone in cerebral arteries was on the order of - 35 change in diameter; addition of atrial natriuretic factor or atriopeptin III in cumulative doses from 10(-10) to 10(-7) M did not produce any transient or sustained changes in diameter. Similarly, atrial natriuretic factor or atriopeptin III did not alter the contractile responses of cerebral vessels to serotonin or prostaglandin F2 alpha. Mesenteric arteries, which do not possess an intrinsic myogenic tone, were precontracted with potassium (30 mM), norepinephrine (10(-6) M), or prostaglandin F2 alpha (1.1 X 10(-5) M) and exposed to the synthetic natriuretic peptides, also without effect. Transmural electrical stimulation (0.3-msec pulses; 180 mA; 4/second) relaxed cerebral and contracted mesenteric arteries; preincubation in 10(-7) M atrial natriuretic factor or atriopeptin III did not alter subsequent responses. These observations suggest that the hypotensive action of atrial natriuretic factor cannot be attributed to direct vasodilation of splanchnic or cerebral resistance-sized arteries.
Differential renal function during angiotensin converting enzyme inhibition in renovascular hypertension.
Authors: Jackson B , McGrath B P , Matthews P G , Wong C , Johnston C I
Published: June 2012

Renal function was measured sequentially in 32 patients with proven renovascular hypertension who were treated with the oral angiotensin converting enzyme inhibitor captopril. Renal function was assessed by serial measurement of serum creatinine. Six patients showed acute rises in serum creatinine concentration compatible with acute renal failure. Acute renal failure was confined to those patients with stenosis to a solitary kidney (transplant or native, occurring in 3 of 8 patients) or bilateral renal artery stenosis (occurring in 3 of 13 patients). No rise in serum creatinine concentration was observed in 11 patients with unilateral renal artery stenosis during long-term angiotensin converting enzyme inhibitor therapy. Acute renal failure during angiotensin converting enzyme inhibitor therapy was not related to the degree of blood pressure fall or the plasma angiotensin II level. Eleven patients with renovascular hypertension were followed prospectively with estimation of renal function by 99mTc-diethylenetriaminepentaacetic acid (DTPA) clearance (determined by computer analysis of scintillation camera renography). In six patients with unilateral renal artery stenosis, total 99mTc-DTPA clearance and serum creatinine level remained constant following angiotensin converting enzyme inhibitor therapy, while in five patients with bilateral renal artery stenosis 99mTc-DTPA clearance fell from 40 +/- 9 to 27 +/- 5 ml/min (p less than 0.05). Split renal function studies revealed that 99mTc-DTPA clearance fell in most kidneys with stenosed arteries during angiotensin converting enzyme inhibition, including the stenosed kidney from patients with unilateral renal artery stenosis (16 stenosed kidneys studied; change in Tc-DTPA clearance, -7.5 +/- 2.7 ml/min).(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of long-term treatment with indomethacin on renal function.
Authors: Ruilope L M , Garcia Robles R , Paya C , Alcazar J M , Miravalles E , Sancho-Rof J , Rodicio J , Knox F G , Romero J C
Published: June 2012

The prolonged effects (42 days) of indomethacin treatment on the renin-angiotensin-aldosterone axis, renal hemodynamics, and renal excretory function in humans were studied. Indomethacin produced a 41% sustained depression in the 24-hour excretion of prostaglandin E2 and a mild (7%) decrease in inulin clearance but did not affect the clearance of p-aminohippurate, the 24-hour excretion of sodium and potassium, or the basal values of plasma aldosterone; however, it decreased the basal values of renin and prevented the stimulated (3 hours of walking) responses of plasma renin activity and plasma aldosterone. Indomethacin also produced a decrease in both the diuretic and saluretic response to furosemide and in the renal ability to concentrate urine. The indomethacin-induced hyporeninism and hypoaldosteronism were more pronounced when the subjects were receiving a sodium-restricted diet. This finding indicates that prolonged administration of anti-inflammatory drugs induces chronic hyporeninism and hypoaldosteronism. Prolonged treatment with indomethacin also produced some of the symptoms of a syndrome of hypoprostaglandinism, such as decreased plasma renin activity, plasma aldosterone, and urinary prostaglandin E2 in association with increases in plasma potassium levels and diastolic pressure.
Localization of specific binding sites for atrial natriuretic factor in peripheral tissues of the guinea pig, rat, and human.
Authors: Mantyh C R , Kruger L , Brecha N C , Mantyh P W
Published: June 2012

Specific, high affinity atrial natriuretic factor (ANF) binding sites were identified and localized by autoradiographic techniques in peripheral tissues of the guinea pig, rat, and human. In the guinea pig kidney, high concentrations of ANF binding sites were located in the glomerular apparatus, outer medulla, and small renal arteries. Other peripheral tissues containing ANF binding sites included the zona glomerulosa of the adrenal cortex, the smooth muscle layer of the aorta and gallbladder, the lung parenchyma, the posterior lobe of the pituitary, the ciliary body of the eye, and the leptomeninges and choroid plexus of the brain. The distribution of ANF binding sites in the rat and human kidney was nearly identical to those seen in the guinea pig kidney; high concentrations were present in the glomerular apparatus, outer medulla, and small renal arteries. These results are consistent with earlier physiological and pharmacological studies that suggested that ANF plays a functional role in the regulation of extracellular fluid volume and blood pressure. There appears to be little species variation in the location and concentration of renal ANF binding sites, suggesting that, at least in the kidney, the results in experimental animals are relevant to the actions of ANF in humans. The finding that ANF binding sites were stable and present in high concentrations in human postmortem kidneys further suggests that these tissues may be amenable to testing for the involvement of ANF receptor dysfunction in diseases such as hypertension and congestive heart failure.
Is beta 1-antagonism essential for the antihypertensive action of beta-blockers?
Authors: Vincent H H , Man in 't Veld A J , Boomsma F , Derkx F H , Schalekamp M A
Published: June 2012

Both nonselective beta-blockers and beta 1-selective blockers are effective antihypertensive agents. beta 1-Blockade generally is considered to be responsible for their antihypertensive action, whereas beta 2-blockade is regarded as undesirable. These common assumptions notwithstanding, the mechanism by which beta-blockers lower blood pressure remains unknown. To examine the possibility that beta 2-blockade may contribute to the antihypertensive action of beta-blocker therapy, we studied the cardiovascular effects of compound ICI 118551, a beta 2-selective blocker. First, we showed that 50 mg t.i.d. orally is a beta 2-selective dose. In contrast to propranolol, 80 mg t.i.d., or atenolol, 100 mg once a day, 50 mg of ICI 118551 t.i.d. failed to block beta 1-mediated inotropic stimulation and stimulation of renin by isoproterenol. We then performed a double-blind, placebo-controlled trial in patients with mild essential hypertension to compare this compound with propranolol, 80 mg t.i.d., and showed that ICI 118551 significantly decreased systolic and diastolic blood pressure. This antihypertensive effect was demonstrated by direct as well as by indirect blood pressure measurements. Thus, contrary to prevailing thought, beta 2-blockade has an antihypertensive effect independent of, and distinct from, beta 1-blockade.
Antihypertensive and volume-depleting effects of mild exercise on essential hypertension.
Authors: Urata H , Tanabe Y , Kiyonaga A , Ikeda M , Tanaka H , Shindo M , Arakawa K
Published: June 2012

After a general clinical observation period of over 4 weeks, 20 essential hypertensive subjects (Japanese) were randomly divided into two groups. One group (n = 10; 4 men and 6 women; 51.4 +/- 2.8 years of age) agreed to physical training using bicycle ergometer exercise with the intensity at blood lactate threshold for 60 minutes three times a week for 10 weeks, while the other group (n = 10; 4 men and 6 women; 51.0 +/- 2.9 years of age) did no particular physical training and was followed once a week as the control. Changes in blood pressure, hemodynamics, and humoral factors of the exercised group were compared with values in the controls. The following significant changes were found only in the exercised group. Blood pressure was significantly (p less than 0.01) reduced. Whole blood and plasma volume indices were significantly reduced (p less than 0.05, p less than 0.01, respectively). The change in ratio of serum sodium to potassium positively correlated with the change in systolic blood pressure (r = 0.76, p less than 0.02). Plasma norepinephrine concentrations both at rest and at the workload of blood lactate threshold during graded exercise tests were significantly reduced (p less than 0.05, p less than 0.02 respectively) after 10 weeks of exercise training. The change in the resting level of plasma norepinephrine positively correlated with that in the mean blood pressure. No such changes were observed in the control group. In both groups, body weight and urinary sodium excretion showed no statistically significant changes.(ABSTRACT TRUNCATED AT 250 WORDS)
Characterization of vascular relaxant factor released from cultured endothelial cells.
Authors: Lückhoff A , Busse R , Winter I , Bassenge E
Published: June 2012

Cultured bovine endothelial cells were grown on microcarrier beads. Columns (0.2 ml) packed with microcarriers were perfused with oxygenated (20% O2) Tyrode's solution containing indomethacin (10 microM), and the effluent was passed through precontracted, endothelium-denuded detector arteries. When the endothelial cells were stimulated with bradykinin (3-100 nM), adenosine 5'-triphosphate (0.3-30 microM), or calcium ionophore A23187 (10-300 nM), they released dose-dependently a nonprostanoid compound that dilated the detector vessel. The factor, probably identical to the endothelium-derived relaxing factor of native endothelium, evoked dilations of the same magnitude in different types of detector vessels (rabbit thoracic aorta, rabbit femoral artery, canine coronary artery). However, this relaxant factor was significantly more effective in arteries precontracted by norepinephrine or serotonin than in arteries precontracted by potassium depolarization. Thus, its dilator action resembles that of the nitrovasodilators. The factor is labile, with an apparent half-life in the range of 20 to 30 seconds. Its dilator potency was inhibited by dithiothreitol (0.2 mM), metyrapone (0.2 mM), nordihydroguaiaretic acid (20 microM), and hemoglobin (1 microM), all of which apparently inactivated the factor. Synthesis or release (or both) of the relaxant factor was abolished by methylene blue (1 microM). High PO2 levels (greater than 400 mm Hg) in the perfusate markedly reduced the release of the relaxant factor from the cultured cells. This study demonstrates that a vascular relaxant factor is released from endothelial cells in monoculture by adenosine 5'-triphosphate, bradykinin, and A23187 and establishes such a culture as a useful tool for analyzing the mechanisms of endothelium-dependent vasomotion.
Paroxysmal hypertension due to sinoaortic baroreceptor denervation in humans.
Authors: Aksamit T R , Floras J S , Victor R G , Aylward P E
Published: June 2012

A 41-year-old man with a remote history of neck and mediastinal radiation was seen with severe paroxysms of hypertension, headache, and cutaneous flushing after bilateral carotid bypass surgery. Investigation revealed marked parallel fluctuations in blood pressure and heart rate and elevation of plasma norepinephrine to 1164 pg/ml during a paroxysm. We systematically evaluated his arterial and cardiopulmonary baroreceptor reflex function by assessing changes in heart rate, arterial pressure, and efferent muscle sympathetic nerve activity, which was measured directly by the microneurographic technique. Elevating resting arterial pressure from 130/88 to 164/100 mm Hg with phenylephrine or lowering it to 88/56 mm Hg with nitroprusside produced no reflex changes in heart rate or efferent sympathetic nerve activity. In contrast, decreases in cardiac filling pressures with lower body negative pressure produced a marked increase in sympathetic nerve activity. These findings indicate complete loss of the afferent limb of the arterial baroreceptor reflex but preservation of the cardiopulmonary baroreceptor reflex. They suggest that both carotid and aortic baroreceptors were impaired by the previous radiation and surgery. Despite the loss of arterial baroreceptor function, the patient did not have sustained hypertension. The paroxysms of hypertension appear to be due to spontaneous fluctuations in central sympathetic drive not buffered by arterial baroreceptors in a manner similar to that seen in sinoaortic-denervated animals.
Enhanced cerebral vascular regulation occurs by age 4 to 5 weeks in spontaneously hypertensive rats.
Authors: Bohlen H G
Published: June 2012

Although the primary emphasis of research on spontaneously hypertensive rats (SHR) tends to be on adult animals, the young SHR can have a mean arterial pressure that is elevated above normal almost proportionately as much as in adult SHR. This study attempted to determine whether the cerebral vasculature of 4- to 5-week-old SHR used existing normal mechanisms to tolerate hypertension or had microvascular characteristics uniquely suited for hypertensive life. At mean arterial pressures above about 60 mm Hg, the arterioles of SHR were constricted compared with similar branch order vessels of normal Wistar-Kyoto rats (WKY). At arterial pressures below 60 mm Hg, however, the inner diameters of arterioles in normal and hypertensive rats can be similar. At arterial pressures of 40 to 120 mm Hg, normal WKY maintained blood flow within +/- 10 of that at the resting arterial pressure of 90 mm Hg; SHR with a mean arterial pressure of 120 mm Hg regulated blood flow over a pressure range of 60 to 160 mm Hg. Normal WKY had petechial hemorrhages from venules and sustained loss of arteriolar tone at arterial pressures above 120 mm Hg, which is the resting arterial pressure of 4- to 5-week-old SHR. Microvascular pressure measurements indicated that the resistance of cerebral arteries was increased, because they dissipated about 50% of the arterial pressure in SHR compared with about 40% in WKY.(ABSTRACT TRUNCATED AT 250 WORDS)
Double-blind, placebo-controlled trial of potassium chloride in the treatment of mild hypertension.
Authors: Svetkey L P , Yarger W E , Feussner J R , DeLong E , Klotman P E
Published: June 2012

Epidemiological and experimental data suggest blood pressure-lowering effects of dietary potassium. A randomized, double-blind clinical trial was used to assess blood pressure response to orally administered potassium, 120 mEq/day, and to placebo in 101 adults with mild hypertension. Blood pressure was measured with a random-zero sphygmomanometer every 2 weeks of this 8-week trial. Systolic blood pressure in the potassium-treated group decreased by 6.4 +/- 13.7 (SD) mm Hg (p less than or equal to 0.025) compared with 0.11 +/- 13.0 mm Hg in the placebo-treated group (p = 0.96). Diastolic blood pressure in the potassium-treated group decreased by 4.1 +/- 8.3 mm Hg (p less than or equal to 0.05) compared with a 1.6 +/- 6.5 mm Hg decrease in placebo-treated subjects (p = 0.09). Baseline blood pressure of potassium-treated subjects was unexpectedly higher than that of controls. After correcting for baseline variation, blood pressure still decreased 3.4/1.8 mm Hg more in potassium recipients than in placebo recipients (p = 0.14 and 0.24, respectively). Blood pressure decreased by 19/13 mm Hg in five blacks taking potassium versus a 1/0 mm Hg increase in seven blacks taking placebo. Compliance with the potassium regimen was 91.5% by pill count; only one subject discontinued treatment because of side effects. In conclusion, 120 mEq/day of microencapsulated potassium chloride was well tolerated in adults with mild hypertension. An antihypertensive effect of potassium cannot be ruled out despite the fact that there was no statistically significant difference between potassium-treated and placebo-treated subjects after adjustment for differences in baseline blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
Renovascular hypertension identified by captopril-induced changes in the renogram.
Authors: Geyskes G G , Oei H Y , Puylaert C B , Mees E J
Published: June 2012

Radioisotope renography was performed in 21 patients with hypertension and unilateral renal artery stenosis with and without premedication with 25 mg of captopril, and the results were compared with the effect of percutaneous transluminal angioplasty on the blood pressure, assessed 6 weeks after angioplasty. Angioplasty caused a considerable decrease in blood pressure in 15 of the 21 patients. In 12 of these 15 patients, captopril induced changes in the time-activity curves of the affected kidney only, suggesting deterioration of the excretory function of that kidney, while the function of the contralateral kidney remained normal. After angioplasty the asymmetry in the time-activity curves diminished despite identical pretreatment with captopril. Such captopril-induced unilateral impairment of the renal function was not seen in the six patients with unilateral renal artery stenosis whose blood pressure did not change after percutaneous transluminal angioplasty or in 13 patients with hypertension and normal renal arteries. The functional impairment of the affected kidneys was characterized by a decrease of 99mTc-diethylenetriamine pentaacetic acid uptake and a delay of 131I-hippurate excretion, while the 131I-hippurate uptake remained unaffected. These data are in agreement with a reduced glomerular filtration rate and diuresis during preservation of the renal blood flow, changes that can be expected after converting enzyme inhibition in a kidney with low perfusion and an active, renin-mediated autoregulation of the glomerular filtration rate. These data suggest that functional captopril-induced unilateral changes, shown by split renal function studies with noninvasive gamma camera scintigraphy, can be used as a diagnostic test for renovascular hypertension caused by unilateral renal artery stenosis.(ABSTRACT TRUNCATED AT 250 WORDS)