bluuebunny/crossref_metadata_2025 huggingface dataset:
Sodium and glucose transport across renal brush border membranes of Milan hypertensive rats.
Authors: Parenti P , Hanozet G M , Bianchi G
Published: June 2012

Sodium transport across luminal membranes of proximal tubules isolated from the kidney cortex of young, prehypertensive rats of the Milan hypertensive strain (MHS) and their corresponding normotensive controls, the Milan normotensive strain (MNS), was measured. A higher sodium uptake was observed in vesicles from MHS, although membrane preparations from both strains behaved similarly as far as enzyme profile and sodium-dependent glucose transport were concerned. In the presence of an inwardly directed sodium gradient, sodium uptake depended on the relative permeability of the counterion: in the presence of 100 mM NaCl, sodium transport in MHS was 26% higher than that in normotensive controls (p less than 0.05). Also, a significantly faster sodium uptake by membrane vesicles from MHS was observed when a pH gradient and an electrical potential difference (inside-negative) were imposed across the membrane. In this condition, sodium uptake by membrane vesicles from MHS was up to 39% higher than that in control MNS (p less than 0.01). Therefore, the difference in sodium transport observed between preparations of luminal membrane from the proximal tubule of MNS and MHS seems to be due to a higher rheogenic sodium pathway in the MHS. The present results are in keeping with previous data showing an increased sodium transport across renal tubules of the MHS and support the hypothesis that the abnormality in sodium and water handling by kidneys from MHS can be related to an alteration in sodium transport across the luminal membrane of the proximal tubule cells.
Dietary calcium and blood pressure in National Health and Nutrition Examination Surveys I and II.
Authors: Sempos C , Cooper R , Kovar M G , Johnson C , Drizd T , Yetley E
Published: June 2012

It has recently been reported that a low intake of calcium may be a risk factor for hypertension. In view of the contradictory results, even when the same survey data base has been used by different researchers, an in-depth analysis was undertaken of the data provided by the two cycles of the National Health and Nutrition Examination Survey (NHANES). Both surveys, conducted in consecutive 4-year intervals during the 1970s, were designed to examine representative samples of the U.S. civilian noninstitutionalized population. The overall descriptive findings in relation to mean blood pressure and calcium intake were virtually identical in the two surveys. Based on "quantile" analysis, neither mean levels of blood pressure nor the prevalence of hypertension was related to calcium intake. Only among black men in NHANES I was a relationship between calcium intake and blood pressure noted. This finding was not apparent among black men in NHANES II or among any of the other sex-race groups in either survey. We conclude that the data of NHANES I and II do not show an association between low calcium intake and blood pressure.
Controlled trial of long-term oral calcium supplementation in essential hypertension.
Authors: Strazzullo P , Siani A , Gugliemi S , Di Carlo A , Galletti F , Cirillo M , Mancini M
Published: June 2012

A randomized, double-blind, placebo-controlled crossover trial of oral calcium supplementation was carried out in 18 patients with uncomplicated essential hypertension. After 15 weeks of oral calcium supplementation, 1 g/day, of the patients' habitual diet, the only blood pressure change (compared with the results of placebo treatment) was in the average standing systolic blood pressure, which was significantly reduced (-8.6 mm Hg; p less than 0.01). The 24-hour urinary calcium excretion and the total serum calcium concentration increased significantly during calcium supplementation (p less than 0.05), indicating good compliance with the treatment. The individual blood pressure changes with high calcium intake were found to be inversely related to basal 24-hour urinary calcium excretion (r = -0.69, p less than 0.001 for standing systolic pressure; r = -0.55, p less than 0.002 for standing diastolic pressure). This correlation was independent of age, basal blood pressure, serum calcium concentration, basal 24-hour urinary sodium excretion, and body weight changes during the trial. In particular, a subgroup of six patients, who had a basal 24-hour urinary calcium excretion higher than the mean + 2 SD of a reference healthy population previously described, showed a substantial average blood pressure fall at variance with the other patients in the study. These results do not support the usefulness of an oral calcium supplement in the majority of subjects with mild essential hypertension; however, they suggest that a group of patients with a previously reported abnormality of calcium metabolism may be responsive to this therapeutic measure.
Similarities of essential and spontaneous hypertension. Volume and number of blood cells.
Authors: Bruschi G , Minari M , Bruschi M E , Tacinelli L , Milani B , Cavatorta A , Borghetti A
Published: June 2012

Spontaneously hypertensive rats have long been used as an animal counterpart of human essential hypertension. The validation of this strain as a model rests mainly on the "clinical" similarity of the two syndromes, but it has scarcely been founded on numerical comparison of measurable parameters. We investigated three hematological indexes previously recognized to be altered in spontaneously hypertensive rats: the single-cell volume of erythrocytes, the single-cell volume of platelets, and the erythrocyte number. Erythrocyte volume was lower by 7%, platelet volume was higher by 12%, and erythrocyte count was higher by 22% in spontaneously hypertensive rats in comparison with Wistar-Kyoto controls. More unexpectedly, it was found that erythrocyte volume is lower by 2%, platelet volume is higher by 3%, and erythrocyte number is higher by 6% in essential hypertensive subjects when compared with normotensive healthy subjects. These results, combined with previously reported blood cell alterations in subjects and rats, reinforce the evidence of a biological similarity between essential and spontaneous hypertension.
Regulation of primate angiotensin II receptors during altered sodium intake.
Authors: Platia M P , Catt K J , Hodgen G D , Aguilera G
Published: June 2012

In the rat, angiotensin II receptors of the adrenal glomerulosa and smooth muscle undergo reciprocal regulatory changes that parallel the changes in target cell sensitivity to angiotensin II during altered sodium intake. In primates, the relative importance of angiotensin II receptor regulation during sodium-induced changes in angiotensin II sensitivity is not clear. To evaluate the role of angiotensin II receptor regulation in the primate, we analyzed the changes in angiotensin II receptors of adrenal and bladder membrane-rich particles after 4 to 6 days of high or low sodium intake in the monkey (Macaca fascicularis). Consistent with the decreased pressor response to angiotensin II, smooth muscle angiotensin II receptors were fewer in sodium-restricted monkeys (93 +/- 17 fmol/mg) than in sodium-loaded monkeys (171 +/- 6 fmol/mg). However, in contrast to the rat, changes in zona glomerulosa angiotensin II receptors in monkey adrenal were similar to those in smooth muscle, decreasing with sodium restriction and increasing with sodium loading (344 +/- 64 and 660 +/- 68 fmol/mg, respectively). There was no change in angiotensin II receptor affinity in either smooth muscle or adrenal particles during altered sodium intake. Concomitant with the decrease in adrenal angiotensin II receptors, 18-hydroxylase activity was increased twofold in adrenal mitochondria from sodium-restricted monkeys (74 +/- 8 fmol/mg/min) compared with sodium-loaded animals (28 +/- 11 fmol/mg/min). The increased sensitivity of the primate adrenal to angiotensin II despite a fall in angiotensin II receptors indicates that full activation of steroidogenesis by angiotensin II can be maintained with partial receptor occupancy.(ABSTRACT TRUNCATED AT 250 WORDS)
Management of hypertension in high school students by using new salt titrator tape.
Authors: Tochikubo O , Sasaki O , Umemura S , Kaneko Y
Published: June 2012

In a blood pressure screening program involving 6589 high school students, 180 male (4.7%) and 17 female (0.6%) students were identified as borderline hypertensive. The 174 hypertensive male adolescents studied further showed pathophysiological features such as a significantly higher frequency of obesity, higher 24-hour urinary sodium excretion, higher hematocrit value, higher sodium and lower potassium concentration in red blood cells, and higher ouabain-sensitive sodium efflux compared with the control group (231 male students; p less than 0.05). When used alone, the ordinary 10-week period of counseling about a low salt diet failed to significantly reduce the blood pressure of hypertensive students. However, when education and counseling efforts were combined with self-monitoring of salt (chloride) excretion in overnight urine samples using a new salt titrator tape developed in our laboratory, 24-hour urinary sodium excretion, weight, and blood pressure decreased significantly over 10 weeks (mean reduction: 52 mEq/day for 24-hour urinary sodium excretion, 1.7 kg for weight, 12/7 mm Hg for blood pressure). These results indicate that blood pressure of borderline hypertensive adolescents could be effectively reduced with this nonpharmacological method of dietary education. Such systematic management might be of importance for the prevention of essential hypertension.
Felodipine, blood pressure, and cardiovascular reflexes in hypertensive humans.
Authors: Smith S A , Mace P J , Littler W A
Published: June 2012

The influence of acute and chronic treatment with felodipine on ambulatory intra-arterial blood pressure, certain cardiac reflexes, and plasma renin activity was studied in nine patients with essential hypertension. Acute oral administration of the drug caused a significant reduction in blood pressure associated with an increase in heart rate mediated by the sinoaortic baroreceptor-heart rate reflex. After 1 week of treatment reflex resetting had occurred, returning heart rate to normal despite continuing blood pressure reduction. This effect was maintained throughout 6 weeks of treatment. Withdrawal of treatment was followed by return of the blood pressure to control levels associated with significant bradycardia caused by reflex reactivation at its reset level. No change was observed in response to tilting or Valsalva's maneuver or in plasma renin activity. Ambulatory intra-arterial data suggested that the clinically useful antihypertensive action of felodipine persists for 9 hours.
Metabolic characteristics of aorta from spontaneously hypertensive and renal and deoxycorticosterone acetate-salt hypertensive rats.
Authors: Seidel C L , Strong R
Published: June 2012

The purpose of this study was to determine if any changes occurred in the basal and stimulated rates of oxygen consumption and lactate production of thoracic aortas from spontaneously hypertensive rats (SHR) and renal and deoxycorticosterone acetate (DOCA)-salt hypertensive rats, and, if so, whether these changes were similar in these three models of hypertension. Rings of thoracic aorta were placed in an isothermic (37 degrees C) muscle bath, and isometric tension development, oxygen consumption, and lactate production were measured. The results indicated that under basal conditions oxygen consumption, but not lactate production, was higher in aortas from all three hypertensive models; the elevation above control was greatest in the renal model (95%) and smallest in SHR (34%). On stimulation with 60 mM KCl, a significant increase in oxygen consumption above basal value occurred in all aorta samples (p less than 0.05); however, lactate production was increased above basal only in aortas from hypertensive animals. Only in aortas from renal and DOCA-salt models was the rate of oxygen consumption during stimulation significantly greater than that of their normotensive controls (p less than 0.05). Developed active stress in response to KCl was the same in all groups, and when the change in lactate production or oxygen consumption was expressed relative to the amount of active stress developed, no differences were observed. These results suggest that, 1) compared to values in aortas from normotensive animals, only the basal rate of oxygen consumption is higher; 2) this higher level of basal metabolic activity is not associated with an alteration in the metabolic cost of force development.(ABSTRACT TRUNCATED AT 250 WORDS)
Aldosterone excretion rates in children and adults during sleep.
Authors: Pratt J H , Miller J Z , Fineberg N S , Parkinson C A
Published: June 2012

The present study undertook to examine aldosterone excretion during sleep as an integrated measurement of aldosterone production. A 24-hour urine collection was divided into awake and sleep fractions. Urinary aldosterone and electrolyte excretion were measured in 26 healthy children (mean age, 8.9 +/- 1.9 [SD] years) and 28 adults (mean age, 29.9 +/- 9.5 years). Aldosterone excretion in children was 5.6 +/- 3.9 (SD) micrograms/g creatinine during the awake period, which was significantly different from the 3.9 +/- 4.1 micrograms/g creatinine value recorded during sleep (p less than 0.002). In adults, awake aldosterone excretion was significantly greater than that during sleep; 4.9 +/- 2.7 versus 3.2 +/- 1.6 micrograms/g creatinine (p less than 0.001). Sleep aldosterone excretion values were highly correlated with the corresponding 24-hour aldosterone excretion values (r = 0.85, p less than 0.001) in children and in adults (r = 0.64, p less than 0.001). Sleep aldosterone excretion was correlated with 24-hour potassium excretion (p less than 0.02) only in children. Sleep aldosterone excretion correlated with neither sleep nor 24-hour sodium excretion in children or adults. Sleep electrolyte excretion rates were highly correlated with 24-hour excretion rates in both children and adults. Dexamethasone, 1 mg, administered the night before to suppress the normally high morning levels of endogenous adrenocorticotropic hormone, had no discernible effect on sleep aldosterone excretion. These results indicate that measurement of aldosterone excretion in an easily collected sleep urine sample provides a reliable index of aldosterone production in children and adults.
Platelet-activating factor stimulates prostaglandin synthesis in cultured cells.
Authors: Kawaguchi H , Yasuda H
Published: June 2012

The effects of platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) on phospholipase activity were studied in aortic smooth muscle cells and renal epithelial cells. When platelet-activating factor was added to cells prelabeled with [3H]arachidonic acid, it induced rapid hydrolysis of phospholipids. Up to 28% of incorporated [3H]arachidonic acid was released into the medium from both aortic and renal cells. A transient rise of diacylglycerol was also seen after the addition of platelet-activating factor to these cells. The accumulation of diacylglycerol and monoacylglycerol was relatively small when compared with the total amount of released free arachidonic acid. The amount of [3H]arachidonic acid released was comparable to the loss of phosphatidylcholine, phosphatidylinositol, and phosphatidylethanolamine, which indicates that platelet-activating factor stimulates phospholipase A2 and C activity in aortic smooth muscle cells and renal epithelial cells. Platelet-activating factor also enhanced prostaglandin biosynthesis in these cells.
Renal effects of diltiazem in primary hypertension.
Authors: Sunderrajan S , Reams G , Bauer J H
Published: June 2012

Although the calcium channel blocker diltiazem has been shown to be an effective antihypertensive agent, its effect on renal function, salt and water excretion, and body fluid composition has not been well characterized in patients with primary hypertension. Therefore, these parameters were prospectively studied in 18 subjects with primary hypertension after placebo and 8 weeks of diltiazem monotherapy. Diltiazem monotherapy was confirmed to be an effective antihypertensive agent. Although mean arterial pressure was reduced from 121 to 108 mm Hg, diltiazem had no overall effect on glomerular filtration rate, renal plasma blood flow, salt and water excretion, or body fluid composition. Renal vascular resistance, however, was decreased. In subjects with pretreatment glomerular filtration rates of 80 ml/min/1.73 m2 or less, diltiazem therapy was associated with marked improvement in glomerular filtration rate (48%) and effective renal plasma flow (36%). Since the filtration fraction was unchanged, changes in glomerular filtration rate may have been related to the attenuated intrarenal effects of angiotensin II or norepinephrine, or both.
Cardiovascular effects of atrial natriuretic factor in anesthetized and conscious dogs.
Authors: Kleinert H D , Volpe M , Odell G , Marion D , Atlas S A , Camargo M J , Laragh J H , Maack T
Published: June 2012

Atrial natriuretic factor lowers blood pressure in normotensive and hypertensive animal models. The present study examined the mechanism of the blood pressure-lowering effect in 10 normotensive dogs. Four awake dogs previously instrumented with electromagnetic flow probes for measurement of cardiac output and catheters for systemic hemodynamic and cardiac dynamic measurements were studied. After a 30-minute control period, a 3 micrograms/kg bolus followed by 0.3 micrograms/min/kg of a 24-residue synthetic atrial natriuretic factor was infused for 30 minutes, followed by a 1-hour recovery period. Mean arterial pressure fell significantly during infusion (control, 125 +/- 4; infusion, 108 +/- 5; recovery, 125 +/- 9 mm Hg; p less than 0.05) and was accompanied by a slight but significant bradycardia (control, 144 +/- 7; infusion, 134 +/- 5; recovery, 145 +/- 7 beats/min; p less than 0.05). Significant reductions in cardiac output (control, 2.66 +/- 0.60; infusion, 2.18 +/- 0.60; recovery, 2.74 +/- 0.60 L/min; p less than 0.05), stroke volume (control, 18.4 +/- 3.9; infusion, 16.0 +/- 4.2; recovery, 19.0 +/- 3.7 ml/beat; p less than 0.05), and maximum increase in rate of change of left ventricular systolic pressure (control, 2475 +/- 200; infusion, 2088 +/- 216; recovery, 2487 +/- 243 mm Hg/sec; p less than 0.05) were also observed during infusion. No significant changes in total peripheral resistance or central venous pressure were noted, although the latter tended to fall during infusion. A similar pattern was observed in six pentobarbital-anesthetized dogs, except that infusion of atrial natriuretic factor did not induce bradycardia.(ABSTRACT TRUNCATED AT 250 WORDS)
Are hypertensive effects of aldosterone, angiotensin, vasopressin, and norepinephrine chronically additive?
Authors: Cowley A W , Skelton M M , Merrill D C
Published: June 2012

The effects of chronic combined administration of angiotensin II, norepinephrine, aldosterone, and arginine vasopressin were compared with the response to each of these hormones administered alone. The studies were performed in dogs to determine the extent to which moderately inappropriate elevations of these hormones could enhance each other's ability to produce chronic hypertension and influence Na and water homeostasis. Blood pressure sensitivity to Na intake was also evaluated by infusing the hormones for 11 days at normal levels of Na intake followed by 11 days at high Na intake with ad libitum drinking. Combined hormone administration did not enhance each hormone's singular hypertensive actions. With aldosterone infusion alone and normal Na intake, mean arterial pressure rose nearly 15 mm Hg and an additional 3 mm Hg during high Na intake. Combined hormone infusion also resulted in a nearly 15 mm Hg rise during normal Na intake and an additional 3 mm Hg rise in mean arterial pressure during high Na intake. Marked Na retention and hypernatremia were observed with aldosterone infusion, while hyponatremia characterized arginine vasopressin infusion. The combined hormone infusion resulted in a tendency toward hypernatremia, although daily Na balance was not significantly changed. Daily water turnover was substantially increased and urine osmolality fell to hypoosmotic levels, despite elevated arginine vasopressin levels. Even with high Na intake, dogs receiving either angiotensin II, arginine vasopressin, or norepinephrine at the same concentrations showed 4 to 10 mm Hg increases in mean arterial pressure. Thus, humoral summation or synergism of these hormones probably does not play a major role in the development of chronic hypertension.
Bumetanide-sensitive sodium-22 transport in vascular smooth muscle cell of the spontaneously hypertensive rat.
Authors: Tokushige A , Kino M , Tamura H , Hopp L , Searle B M , Aviv A
Published: June 2012

The effect of bumetanide, a known probe of Na+, K+ cotransport, on 22Na+ uptake and washout was examined in serially passed cultured vascular smooth muscle cells of spontaneously hypertensive rats (SHR), Wistar-Kyoto rats (WKY), and Wistar rats. In Ca2+-deficient medium, the drug exerted the greatest effect on 22Na+ washout in vascular smooth muscle cells from SHR and the least effect on cells from WKY. The respective mean values for the apparent bumetanide-sensitive 22Na+ washout rate constants (Ke; X 10(-2)/min) were 7.2, 4.3, and 1.7 for cells from SHR, WKY, and Wistar rats. In both 1 mM Ca2+ and Ca2+-deficient medium, in the presence of 1 mM ouabain, vascular smooth muscle cells from SHR had the highest plateau phase of 22Na+ uptake among the three cell preparations. All cells exhibited higher 22Na+ uptake in Ca2+-deficient medium than in 1 mM Ca2+ medium. Under this condition, bumetanide caused an additional rise in steady state 22Na+ uptake that was most pronounced in cells from SHR (21.3% versus 16.6% for Wistar rats and 4.8% for WKY). This finding indicates that a quantitatively greater inhibition of washout than of the uptake component of the bumetanide-sensitive 22Na+ transport occurs in Ca2+-deficient medium. It is concluded that, in Ca2+-deficient medium, the bumetanide-sensitive 22Na+ washout is higher in vascular smooth muscle cells of SHR than in those of normotensive controls and that this phenomenon reflects a higher Na+ turnover in vascular smooth muscle cell in the hypertensive rat strain.
Effects of converting enzyme inhibition on split renal function in renovascular hypertension.
Authors: Miyamori I , Yasuhara S , Takeda Y , Koshida H , Ikeda M , Nagai K , Okamoto H , Morise T , Takeda R , Aburano T
Published: June 2012

The effects of captopril on effective renal plasma flow and glomerular filtration rate were studied using a noninvasive radioisotopic method on individual kidneys in eight patients with renovascular hypertension and 12 patients with essential hypertension with various renin levels. Four patients with renovascular hypertension had unilateral while three had bilateral renal artery stenosis. The effective renal plasma flow and glomerular filtration rate were determined by using 131I-iodohippurate sodium and 99mTc-diethylenetriamine pentaacetic acid, respectively. Glomerular filtration rate and effective renal plasma flow were significantly reduced in the stenotic kidneys of patients with renovascular hypertension compared with values in nonstenotic kidneys (p less than 0.01). Treatment with captopril, 37.5 to 75 mg/day for 1 to 48 weeks, further reduced the glomerular filtration rate only in stenotic kidneys, and effective renal plasma flow increased in both kidney types. In two of the three renal hypertensive patients with bilateral renal artery stenosis, captopril produced a reversible azotemia that was unrelated to the fall in blood pressure, as evidenced by the lack of azotemia seen after a moderate blood pressure reduction induced by other antihypertensive medications. These results indicate that endogenous angiotensin II is essential in maintaining the glomerular filtration rate in stenotic kidneys and suggest that a reduction in glomerular filtration rate during captopril administration could indicate the presence of renal artery stenosis.
Effects of calcium infusion on blood pressure in hypertensive and normotensive humans.
Authors: Ellison D H , Shneidman R , Morris C , McCarron D A
Published: June 2012

Disorders of calcium and parathyroid hormone homeostasis have been reported in subjects with essential hypertension. In many of these studies, dietary intakes of sodium and calcium were not carefully controlled. The present study was designed to compare calcium and parathyroid hormone homeostasis in normal and hypertensive subjects on controlled dietary sodium and calcium intakes and to examine the impact of dietary sodium loading on hemodynamic and metabolic responses to infused calcium. Seven subjects with essential hypertension and seven age-matched and sex-matched controls were studied while consuming a standard diet containing 600 mg of elemental calcium. Each subject was studied while consuming 10, 160, and 510 mEq of sodium per day, before, during, and after a 3-hour calcium infusion (3.75 mg/kg/hr). Before calcium infusion, hypertensive subjects had increased urinary cyclic adenosine 3',5'-monophosphate excretion independent of sodium intake (p less than 0.05). Urinary potassium excretion was greater in normotensive than in hypertensive subjects (p = 0.002). At baseline, dietary sodium intake had no effect on systolic, diastolic, or mean arterial pressure. During calcium infusion, systolic pressure increased in both groups, whereas diastolic pressure increased only when dietary sodium content was high and mean arterial pressure increased only in hypertensive subjects (p = 0.007). Together, these data provide evidence for interactions between dietary sodium intake and the cardiovascular response to calcium. They confirm that hypertensive subjects exhibit enhanced parathyroid gland function even when dietary factors are controlled, and they suggest that these subjects are more sensitive to the cardiovascular effects of short-term calcium infusion.
Does vasopressin sustain blood pressure in conscious spontaneously hypertensive rats?
Authors: Filep J , Fejes-Tóth G
Published: June 2012

To investigate the possible role of arginine vasopressin in maintaining high blood pressure of spontaneously hypertensive rats (SHR), the effect of two arginine vasopressin pressor antagonists on mean arterial pressure and the pressor responsiveness to exogenous arginine vasopressin were studied in conscious, freely moving SHR and in Wistar-Kyoto rats (WKY). Intravenous injections of either d(CH2)5Tyr(Me)arginine vasopressin, 10 micrograms/kg, or dPTyr(Me)arginine vasopressin, 20 micrograms/kg, had no effect on mean arterial pressure or heart rate of normohydrated SHR, although both antagonists almost completely abolished the pressor response to exogenous arginine vasopressin. Furthermore, dPTyr(Me)arginine vasopressin was ineffective in eliciting a depressor response, even after 24 or 48 hours of water deprivation. During converting enzyme inhibition with SQ 20881, mean arterial pressure and heart rate remained unchanged following arginine vasopressin blockade in both normohydrated and fluid-restricted animals. alpha-Adrenergic receptor blockade reduced the blood pressure of normohydrated SHR, from 160 +/- 7 to 81 +/- 8 mm Hg. When dPTyr(Me)arginine vasopressin was given during alpha-adrenergic receptor blockade there was a small, transient fall in mean arterial pressure. The pressor responsiveness to exogenous arginine vasopressin was similar in hypertensive and normotensive rats. These results suggest that arginine vasopressin does not function as an important pressor hormone in conscious SHR.
Bartter's syndrome and the atrial natriuretic factor gene.
Authors: Graham R M , Bloch K D , Delaney V B , Bourke E , Seidman J G
Published: June 2012

We investigated whether the gene for atrial natriuretic factor, a recently discovered peptide hormone with potent natriuretic, diuretic, and vasorelaxant properties, was pathogenetically linked to an uncommon but well-defined fluid and electrolyte disorder, Bartter's syndrome. Restriction fragment length polymorphisms in the atrial natriuretic factor gene were sought in a large kindred with six of 23 family members being affected. A Bgl II polymorphism, identified in two of 40 (5%) apparently normal subjects, was found in one of two first-generation family members. This polymorphism was also present in five of seven unaffected second-generation siblings but in only three of six affected siblings. The failure of the absence or the presence of the polymorphism to cosegregate with the disease clearly indicates that in this kindred, the gene for atrial natriuretic factor is not linked to Bartter's syndrome.
Alterations in the plasma membrane properties of the myocardium of spontaneously hypertensive rats.
Authors: Sharma R V , Butters C A , Bhalla R C
Published: June 2012

Spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats were used to investigate the adaptive biochemical changes in the myocardium in response to chronic afterload. Ouabain-inhibited Na+,K+-adenosine triphosphatase (ATPase) activity was decreased by 40% in myocardium of SHR compared with that from WKY, which may lead to increased intracellular Ca2+ through Na+-Ca2+ exchange. Similarly, alpha 1-adrenergic receptor density, estimated by [3H]prazosin binding, was decreased by 42% in myocardial membranes of SHR, while the affinity for the agonist and the antagonist was not altered. In contrast, the number of Ca2+ channels estimated by [3H]nitrendipine binding was increased by 45% in myocardial membranes of SHR, while the affinity was comparable between SHR and WKY. These differences between WKY and SHR in the membrane properties were not due to differential contamination of plasma membranes because the activities of other putative plasma membrane marker enzymes were comparable between WKY and SHR. There were no differences between WKY and SHR in the myosin ATPase activity estimated using myofibrils, actomyosin, and myosin. These results suggest that specific alterations have occurred in the plasma membrane properties of myocardium of SHR that result in altered intracellular Ca2+ metabolism. These alterations may have an important bearing on excitation-contraction coupling in myocardium of SHR.
Effects of clonidine on central and peripheral nerve tone in primary hypertension.
Authors: Sullivan P A , De Quattro V , Foti A , Curzon G
Published: June 2012

To define the mechanisms whereby clonidine lowers blood pressure, we measured cerebrospinal fluid and plasma levels of norepinephrine, normetanephrine, epinephrine, dopamine, and the dopamine metabolite homovanillic acid in 10 primary hypertensive subjects before and after 3 months of clonidine treatment (mean dose, 0.68 mg/day). Catecholamines were measured by radioenzymatic methods. Cerebrospinal fluid and plasma sampling was performed after subjects had fasted and remained supine overnight, and plasma sampling was repeated 2 hours later, after subjects had ambulated. Supine and upright blood pressure fell, as might be expected. Cerebrospinal fluid levels of norepinephrine and normetanephrine fell significantly, but dopamine and homovanillic acid levels were unchanged. Plasma norepinephrine, normetanephrine, and epinephrine levels decreased 30 to 50%, and supine dopamine levels also fell. The percent fall in supine blood pressure was related to the fall of cerebrospinal fluid and plasma norepinephrine. There were also positive relationships between the decreases of plasma norepinephrine and of normetanephrine and dopamine. The cerebrospinal fluid/plasma norepinephrine ratio was unaffected by clonidine, suggesting that the drug lowered both pools equally. Our findings indicate that clonidine decreases both central and peripheral norepinephrine activity. The dopaminergic activity of cerebrospinal fluid was unaffected by clonidine, and though plasma dopamine levels tended to be lower after treatment, mean plasma prolactin level, an index of dopaminergic activity, was also unchanged. The fall in plasma epinephrine level is probably related to diminished sympathetic adrenomedullary stimulation and is unlikely to contribute to clonidine's antihypertensive action. These results also suggest that measurement of normetanephrine in cerebrospinal fluid and plasma provides a good index of norepinephrine activity.
Enhanced platelet cyclic AMP response to prostaglandin E1 in essential hypertension.
Authors: Resink T J , Bürgisser E , Bühler F R
Published: June 2012

Platelets provide an accessible and homogeneous cellular system for investigative studies on hypertension. Hypertension-associated abnormalities of cyclic adenosine 3',5'-monophosphate (AMP) metabolism were studied in human platelets. Platelets from hypertensive subjects had an enhanced cyclic AMP accumulation response to prostaglandin E1 (twofold increase in prostaglandin E1 sensitivity). The degree of adenylate cyclase activation in response to both prostaglandin E1 (receptor-mediated) and forskolin (non-receptor-mediated) was greater in hypertensive than normotensive subjects, and prostaglandin E1-stimulated and forskolin-stimulated adenylate cyclase activity correlated directly (r = 0.71, p less than 0.001, n = 26). This finding suggests that the catalytic subunit of the enzyme is the rate-limiting step of this hormonal information transduction. Platelets from hypertensive subjects were more sensitive to epinephrine-induced inhibition of the stimulatory effects of prostaglandin E1 on both cyclic AMP accumulation (fourfold) and activation of cyclic AMP-dependent protein kinase. These findings suggest that the enhanced cyclic AMP metabolic response to prostaglandin E1 in platelets from subjects with established essential hypertension may function as a negative feedback mechanism to protect the cells against calcium overload and to reduce their stimulated participation in hemostatic and thrombotic processes.
Increased aortic DNA synthesis precedes renal hypertension in rats. An obligatory step?
Authors: Loeb A L , Mandel H G , Straw J A , Bean B L
Published: June 2012

The rate of DNA synthesis was determined in rats with developing and established two-kidney, one clip renal hypertension. Rate of DNA synthesis was measured as [3H]thymidine incorporation into DNA per hour. After stenosis of the renal artery, blood pressure increased over a 2-week period. Five days after clipping, there was an increase in the rate of aortic DNA synthesis before an increase in blood pressure was detected, whereas there was no DNA effect in sham-operated animals. This difference in [3H]thymidine incorporation into aortic DNA could not be accounted for by alterations in thymidine pool sizes. The increase in DNA synthesis was still present 3 weeks after renal artery stenosis, although by that time blood pressure had plateaued. The role of DNA synthesis in the development of renal hypertension was investigated by determining whether inhibition of DNA synthesis with cytosine arabinoside could prevent the increase in blood pressure. Treatment of clipped rats with cytosine arabinoside for 5 days delayed the increase in blood pressure for more than 4 days, as compared with the effect of saline treatment in clipped rats. Although the possibility remains that some effect of cytosine arabinoside other than its effect on DNA synthesis could have influenced blood pressure, there were no differences in body weight, food intake, water intake, or urine output between cytosine arabinoside-treated and saline-treated rats with renal artery clips, and cytosine arabinoside treatment had no effect on blood pressure or body weight in normal rats. These results suggest that an increase in DNA synthesis may be an obligatory step in the genesis of renal hypertension.
Norepinephrine removal and release in the forearm of healthy subjects.
Authors: Chang P C , van der Krogt J A , Vermeij P , van Brummelen P
Published: June 2012

The relevance of local removal and release of norepinephrine (NE) for antecubital venous plasma NE concentration was studied in 22 healthy subjects. Arterial and venous plasma NE and forearm blood flow were measured during intra-arterial infusion of two doses of NE, intra-arterial NE infusion with two doses of sodium nitroprusside, intravenous infusion of NE with intra-arterial infusion of four doses of sodium nitroprusside, and lower body negative pressure of -20 mm Hg for 15 minutes. The venous plasma NE concentration-time curves during the infusions of the two doses of NE indicated first-order kinetics for forearm extraction: forearm NE extraction rate during the low dose infusion was 67 +/- 4.1% (SEM) and correlated with basal forearm blood flow (r = -0.64, p less than 0.03, n = 12). Local sodium nitroprusside-induced vasodilatation during the intra-arterial and intravenous NE infusions was accompanied by dose-dependent decreases in forearm extraction rates for NE and epinephrine. During lower body negative pressure, taking into account the high basal forearm extraction rate for NE, local and systemic release of NE was indicated by increases in arterial and venous plasma and the venous-arterial plasma NE concentration difference (p less than 0.05 for all). These data show that removal of NE from forearm circulation is a process with a high extraction ratio obeying first-order kinetics and that this extraction process inversely relates to forearm blood flow. Thus, antecubital venous plasma NE is likely to be derived mainly from local release and not from the arterial plasma NE input.
Role of sympathetic nervous system in hypotensive action of taurine in DOCA-salt rats.
Authors: Sato Y , Ando K , Fujita T
Published: June 2012

We tested the hypothesis that the antihypertensive effects of dietary taurine supplementation in deoxycorticosterone acetate (DOCA)-salt rats may be attributed to the suppression of sympathetic nervous system activity. In uninephrectomized rats treated with DOCA while receiving 1% NaCl solution for 2 weeks, systolic blood pressure was significantly increased as compared with that in control rats treated with vehicle suspension and tap water. Sympathetic nervous system activity was assessed by tissue norepinephrine turnover, which was determined from the rate of decline of tissue norepinephrine concentration after the administration of alpha-methyl-p-tyrosine, a potent inhibitor of the rate-limiting step of catecholamine synthesis. Cardiac and splenic norepinephrine turnover during either normal conditions or cold exposure (4 degrees C, 8 hours) were markedly increased in DOCA-salt rats as compared with control rats. Also, DOCA-salt rats had increased depressor response to hexamethonium bromide, a ganglion blocker. In contrast, supplementation of 1% taurine in DOCA-salt rats attenuated the development of the hypertension associated with the normalization of both the increased depressor response to ganglionic blockade and the accelerated cardiac and splenic norepinephrine turnover during either normal conditions or cold exposure. Taurine supplementation in control rats, however, had no effect on blood pressure or norepinephrine turnover during cold exposure. These results suggest that taurine supplementation suppresses sympathetic overactivity in DOCA-salt rats, thus leading to inhibition of the development of hypertension.
Influence of magnesium on blood pressure and the effect of nifedipine in rats.
Authors: Overlack A , Zenzen J G , Ressel C , Müller H M , Stumpe K O
Published: June 2012

The influence of long-term alterations in dietary magnesium intake on blood pressure and on the antihypertensive effect of the calcium antagonist nifedipine was investigated in normotensive Wistar-Kyoto (WKY) and in spontaneously hypertensive rats (SHR). The rats were fed a diet either high (1%), normal (0.1%), or low (0.01%) in magnesium for 12 weeks (WKY) and 20 weeks (SHR), respectively. Nifedipine was added to the diet for 4 weeks in concentrations of 300 and 1000 ppm. Each dose was given for 2 weeks. Plasma and intraerythrocytic concentrations of sodium, potassium, and magnesium were measured before and at the end of nifedipine treatment. Blood was obtained by cardiac puncture. In the WKY and SHR, blood pressure was not influenced by magnesium intake. The blood pressure-lowering effect of nifedipine was most pronounced on normal dietary magnesium and was significantly suppressed in the magnesium-deficient rats. Plasma and intracellular total magnesium concentrations were consistently increased during high and reduced during low dietary intake of the ion. Intracellular sodium concentration increased during magnesium deficiency and was normalized by nifedipine. The marked and long-term alterations in plasma and intracellular concentrations of magnesium did not influence arterial blood pressure levels in either the normotensive WKY or the SHR. Therefore, dietary magnesium intake does not appear to play an important role in long-term regulation of blood pressure in rats. However, magnesium depletion attenuates the blood pressure-lowering effect of nifedipine.
Blood pressure and physical fitness in children.
Authors: Hofman A , Walter H J , Connelly P A , Vaughan R D
Published: June 2012

The association between physical fitness and blood pressure was studied in 2061 children selected from all fourth graders in 44 elementary schools in the New York City area. Their blood pressure and physical fitness were measured on two consecutive examinations 1 year apart. Systolic and diastolic blood pressure were highest in children with poor physical fitness. The change in physical fitness between the 2 examination years was related to the change in systolic and diastolic blood pressure (i.e., children with a decline in physical fitness showed the largest rise in blood pressure). These observations suggest that the level of systolic and diastolic blood pressure in children is associated with the level of physical fitness. They also indicate that change in blood pressure in childhood may be related to change in physical fitness.
Platelet activating factor vasoconstriction of dog kidney. Inhibition by alprazolam.
Authors: Baer P G , Cagen L M
Published: June 2012

Systemic administration of platelet activating factor (PAF; acetyl glyceryl ether phosphorylcholine) reduces renal blood flow, but the mechanism responsible for that effect has not been defined. To address that problem, we determined the effects on renal blood flow of PAF administered directly into the renal artery in pentobarbital (30 mg/kg)-anesthetized dogs. Bolus injections of PAF (0.2-0.8 microgram) caused transient renal vasoconstriction, reducing renal blood flow by 20 to 60% without altering systemic blood pressure; lyso-PAF (1 microgram) had no effect. The effects of PAF on renal blood flow were not altered by alpha-adrenergic blockade (phentolamine, 3 mg/kg) or by angiotensin II receptor blockade ([Sar1,Ala8]angiotensin II, 6 micrograms/kg/min), but they were increased in magnitude and duration by meclofenamate (5 mg/kg), a cyclooxygenase inhibitor. Methysergide (3 mg/kg), a serotonin antagonist, slightly reduced PAF effects, but a specific blocker of vascular serotonin receptors did not. Renal venous plasma platelet density was not altered by infusion of PAF into the renal artery at a dose (1-2 micrograms/min) that caused a sustained 20% renal blood flow decrease. Alprazolam, a benzodiazepine that competitively inhibited PAF-induced aggregation in canine platelet-rich plasma, also inhibited the renal vasoconstrictor action of PAF (0.8 mg/min, into the renal artery) but did not alter renal vasoconstrictor effects of norepinephrine or angiotensin II.
Role of angiotensin II in the hormonal, renal, and electrolyte response to sodium restriction.
Authors: Rogacz S , Hollenberg N K , Williams G H
Published: June 2012

Adrenal responses to angiotensin II (ANG II) are enhanced with restriction of sodium intake. To determine whether increased circulating ANG II levels are responsible for the enhanced responsiveness, the adrenal and blood pressure responses to ANG II in human subjects were assessed four times: in balance on a high and a low salt diet and before and after the administration of a converting enzyme inhibitor (enalapril). Before enalapril administration, sodium restriction significantly increased (p less than 0.02) plasma renin activity, ANG II, and aldosterone levels; the aldosterone response to ANG II was enhanced twofold (p less than 0.01); and the blood pressure response to ANG II infusion was reduced significantly (p less than 0.05). Despite a fixed and low plasma ANG II concentration when enalapril was employed, the adrenal response to ANG II on the low salt diet was enhanced to the same degree as that observed before administration of the converting enzyme inhibitor. Conversely, enalapril substantially altered the blood pressure response to ANG II with sodium restriction, completely preventing the reduction in responsiveness. If the subjects were first given enalapril and then sodium intake was restricted, ANG II levels did not change significantly but renal excretion of both sodium and potassium was substantially modified. The rate at which renal excretion of sodium fell to match intake was retarded strikingly (p less than 0.001); conversely, renal retention of potassium increased significantly (p less than 0.03) as low salt balance was attained. Possibly because of the potassium retention, aldosterone levels rose, but significantly less than when enalapril was absent.
Renal nerves and the pathogenesis of angiotensin-induced hypertension.
Authors: Vari R C , Zinn S , Verburg K M , Freeman R H
Published: June 2012

The present study examined the role of the renal nerves in the development of hypertension produced by chronic infusion of angiotensin II in the conscious rat. The animals were divided into four groups, and a unilateral nephrectomy was performed. The remaining kidney was denervated in two groups, whereas in the other two groups of animals the nerves were left intact. Four days later either angiotensin II (83 ng/min) or saline infusions were begun through subcutaneously implanted osmotic minipumps. The rats were subsequently studied for 14 days. The results indicate that renal denervation significantly attenuated the pressor response to angiotensin II for approximately 6 days. Following this period, there was no difference in blood pressure between the innervated and denervated rats infused with angiotensin II, as both groups attained a hypertensive level of 170 to 180 mm Hg, which was 60 to 70 mm Hg above the blood pressure of the control rats infused with saline. Kidney norepinephrine content was reduced 95% by the denervation procedure and by 40% following infusion of angiotensin II into rats with intact renal nerves. These data demonstrate that, while the renal nerves appear to play a modulatory role in the development of the hypertension, they are not essential for the pathogenesis to occur nor do they determine the final level of hypertension achieved following chronic infusion of angiotensin II in the rat.