bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of sympathetic efferent nerves in blood pressure regulation and in hypertension.
Authors: Mathias C J
Published: August 2012

This article presents some aspects of the role of sympathetic efferent nerves in the regulation of blood pressure in humans. Lessons have been learned from disorders that cause either sympathetic underactivity or overactivity. In chronic autonomic failure, pressor stimuli (mental arithmetic, isometric exercise, or cold) are unable to raise blood pressure, whereas stimuli that normally activate sympathetic efferent nerves to maintain blood pressure (head-up tilt, exercise, and food ingestion) can cause marked hypotension. Recognition of specific defects, such as the inability to synthesize norepinephrine in isolated dopamine beta-hydroxylase deficiency, suggests that sympathetic nerves may influence blood pressure regulation through nonadrenergic mechanisms (dopamine, neuropeptides, and purines). Tetraplegic patients with high cervical cord transection also have sympathetic impairment and postural hypotension, but this is less of a clinical problem because of compensatory hormonal and other mechanisms. Tetraplegic patients are unique as they also may have severe paroxysmal hypertension because of increased spinal sympathetic reflex activity. The pathophysiological mechanisms responsible for this exaggerated response include changes in postsynaptic adrenergic receptor numbers and their sensitivity, the actions of nonadrenergic cotransmitters, and the lack of sympathoneural pathways from the brain that are severed by the lesion. Finally, the putative role of the sympathetic nervous system in hypertension with unilateral renal artery stenosis, which initially is humorally mediated, is discussed. The centrally acting sympatholytic agent clonidine is effective in lowering blood pressure in renovascular hypertension independently of humoral factors when multiple agents have failed.(ABSTRACT TRUNCATED AT 250 WORDS)
Abnormal renal function and autoregulation in essential hypertension.
Authors: Guyton A C
Published: August 2012

The goal of this presentation has been to emphasize two fundamental mechanisms in the development of essential hypertension. These are: 1) The basic cause of essential hypertension is the inability of the kidneys to excrete an adequate volume of urine at normal arterial pressure. Therefore, fluid accumulates in the body until the pressure rises high enough to balance fluid output with fluid intake. This fluid balancing act is an infinite gain feedback system for controlling arterial pressure to a very precise level determined by the kidneys. Furthermore, this infinite gain allows the kidney mechanism to dominate the other pressure control mechanisms for long-term pressure control. Because of this domination, as long as a person has normal intake of water and electrolytes, essential hypertension cannot develop without an elevated pressure setting of the kidneys. 2) An increase in total peripheral resistance will not cause hypertension as long as the kidneys can still excrete normal amounts of water and electrolytes at normal arterial pressure, because loss of excess fluid volume at high pressures will simply reduce the cardiac output until the pressure falls back to normal. Therefore, what is the cause of the very high total peripheral resistance found in almost all patients with essential hypertension? The answer is likely the long-term blood flow autoregulation mechanism that occurs in virtually all tissues of the body. That is, when the pressure rises too high for whatever reason, this in turn forces too much blood flow through the tissues. In response, the local blood flow control mechanisms all over the body increase the vascular resistances until the flows return to normal.(ABSTRACT TRUNCATED AT 250 WORDS)
Hyperinsulinemia: possible role in obesity-induced hypertension.
Authors: Landsberg L
Published: August 2012

Data in support of the hypothesis that insulin-mediated sympathetic stimulation contributes to the hypertension that occurs in association with obesity are presented. The relation between insulin and the sympathetic nervous system derives from the effect of diet on sympathetic activity. Fasting suppresses but overfeeding stimulates the sympathetic nervous system. Insulin-mediated glucose metabolism within central neurons sensitive to insulin and glucose appears to be one important signal in this relation between diet and sympathetic activity. In the obese, hyperinsulinemia and hypertension track together in epidemiological studies. Evidence from a human population-based study (the Normative Aging Study) indicates that the abdominal form of obesity is associated with both hyperinsulinemia and increased urinary norepinephrine excretion. Elevations in urinary norepinephrine excretion, moreover, were highest in those with the highest fasting levels of insulin and glucose. These observations are consistent with the hypothesis that insulin-mediated sympathetic stimulation is a mechanism recruited in the obese to increase metabolic rate and restore energy balance; concomitant increases in sympathetic stimulation of the heart, vasculature, and kidney result in hypertension, which, according to this formulation, is an unfortunate by-product of the cardiovascular response to a metabolic adaptation.
Hypertension during chronic hyperinsulinemia in rats is not salt-sensitive.
Authors: Brands M W , Hildebrandt D A , Mizelle H L , Hall J E
Published: August 2012

The goal of this study was to examine the chronic blood pressure and renal actions of insulin in conscious rats and to determine whether the blood pressure response to insulin is salt-sensitive. The effects of chronic hyperinsulinemia were examined in three groups of Sprague-Dawley rats given low sodium (LS rats, 0.6 meq/day), normal sodium (NS rats, 3.0 meq/day), or high sodium (HS rats, 11.4 meq/day) intakes. After 5-7 days of acclimation and 4 days of control measurements, insulin was infused 24 hr/day (1.5 milliunit/kg/min i.v.) for 7 days, and euglycemia was maintained by infusion of glucose (22 mg/kg/min i.v.). Mean arterial pressure was recorded continuously 19 hr/day, using computerized techniques, from chronically implanted aortic catheters. Chronic insulin infusion increased arterial pressure similarly in the three groups of rats, from 91 +/- 2 to 104 +/- 4 mm Hg in LS rats (n = 6), from 86 +/- 2 to 104 +/- 4 mm Hg in NS rats (n = 5), and from 91 +/- 2 to 105 +/- 8 mm Hg in HS rats (n = 5). There were no significant changes in plasma renin activity or glucose concentration in any group during insulin infusion. Control sodium excretions were 0.5 +/- 0.1, 2.3 +/- 0.1, and 9.3 +/- 0.6 meq/day in LS, NS, and HS rats, respectively, and there were no significant changes in urinary sodium excretion or cumulative sodium balance during 7 days of insulin infusion in any of the groups. These observations indicate that chronic hyperinsulinemia in rats produced hypertension that was not salt-sensitive and not dependent on sodium retention or increased renin secretion. Moreover, insulin-induced hypertension was associated with a shift of renal pressure natriuresis, since sodium balance was maintained at elevated arterial pressures.
Changes in vascular resistance during carotid occlusion in normal and baroreceptor-denervated rats.
Authors: Machado B H , Bonagamba L G , Castania J A , Menani J V
Published: August 2012

In the present study, we investigated changes in mesenteric, renal, and hindquarter vascular resistance during the pressor response produced by bilateral carotid occlusion (BCO) in conscious, freely moving normal and denervated (aortic, carotid, or both) rats. BCO was performed using special previously implanted cuffs. In control normal rats, the increase in mean arterial pressure (MAP) during early and late responses (37 +/- 4 and 21 +/- 2 mm Hg, respectively) was related to increased renal (125 +/- 12% and 45 +/- 10%) and mesenteric (38 +/- 13% and 41 +/- 5%) but not hindquarter (14 +/- 4% and 8 +/- 7%) vascular resistance. In aortic-denervated rats, the greater MAP increase in early and late responses (57 +/- 4 and 44 +/- 4 mm Hg, respectively) compared with normal rats was related to a marked increase in hindquarter (137 +/- 26% and 106 +/- 26%) and mesenteric (104 +/- 14% and 66 +/- 9%) vascular resistance. In carotid-denervated rats, MAP increase and change in vascular resistance were similar to those values observed in control rats. Sinoaortic-denervated rats showed a greater MAP increase (34 +/- 4 mm Hg) during late response and a reduced increase in renal vascular resistance (46 +/- 6%) during early response.(ABSTRACT TRUNCATED AT 250 WORDS)
Early depression of the baroreceptor sensitivity during onset of hypertension.
Authors: Moreira E D , Ida F , Oliveira V L , Krieger E M
Published: August 2012

We studied the correlation of changes in gain sensitivity of the baroreceptors and the development of resetting of the baroreceptors 2 and 6 days after the onset of hypertension produced by subdiaphragmatic aortic constriction in rats. Mean arterial pressure of anesthetized rats was maintained at approximately the same level as that of conscious rats, and baroreceptor function curves were studied on a beat-to-beat basis by computer. After 2 days of hypertension, the difference between the systolic pressure threshold and the control diastolic pressure was -13 +/- 2 mm Hg (125 +/- 3 versus 138 +/- 4 mm Hg). Individual values showed that in seven of nine hypertensive rats, the difference was less than 15 mm Hg, indicating complete resetting. After 6 days of hypertension, all rats exhibited complete resetting, when the systolic pressure threshold was similar to control diastolic pressure (143 +/- 4 versus 141 +/- 2 mm Hg), indicating that more than 2 days of hypertension is necessary for full displacement of the pressure thresholds when all hypertensive rats are considered. Slopes of the baroreceptor curves after 2 and 6 days of hypertension showed that baroreceptor gain was depressed by 25% and 34%, respectively. The difference was not statistically significant (1.07 +/- 0.054% versus 0.94 +/- 0.049% and 1.43 +/- 0.075% in controls). When changes in pressure were circumscribed to a more physiological range, a depression of 25% in response to +10 mm Hg and 37% in response to -10 mm Hg was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
Angiotensin converting enzyme inhibitors versus calcium antagonists in the treatment of diabetic hypertensive patients.
Authors: Ferder L , Daccordi H , Martello M , Panzalis M , Inserra F
Published: August 2012

Angiotensin converting enzyme inhibitors and calcium antagonists are effective agents for controlling high blood pressure in diabetic patients. We selected 30 type II diabetic patients with proteinuria and evaluated the effect of these drugs on renal function and proteinuria. In a double-blind trial, patients received either 40 mg/day enalapril or 40 mg/day nifedipine during 12 months. They also received a hypoproteic diet with 0.8 g/kg wt/day of protein. In the enalapril group (10 men and eight women), mean arterial blood pressure was 112.0 +/- 12 mm Hg, creatinine clearance was 58.6 +/- 12.4 ml/min, and 24-hour proteinuria was 4.36 +/- 3.23 g/24 hr before treatment. After treatment, mean arterial blood pressure was 82.0 +/- 8.30 mm Hg (p less than 0.001), creatinine clearance was 66.6 +/- 13.8 ml/min (NS), and 24-hour proteinuria was 0.56 +/- 0.78 g/24 hr (p less than 0.001). In the nifedipine group (six men and six women), mean arterial blood pressure was 114.0 +/- 8.0 mm Hg, creatinine clearance was 67.8 +/- 19.6 ml/min, and 24-hour proteinuria was 2.84 +/- 1.31 g/24 hr before treatment. After treatment, mean arterial blood pressure was 86.0 +/- 7.0 mm Hg (p less than 0.001), creatinine clearance was 51.4 +/- 7.9 ml/min (p less than 0.001), and 24-hour proteinuria was 2.66 +/- 0.89 g/24 hr (NS). These results show a similar hypotensive action and different renal effects between these two drugs after 12 months of treatment.
Inhibition of atrial natriuretic peptide-induced natriuresis by plasma hydrolysates containing pepsanurin.
Authors: Borić M P , Croxatto H R , Albertini R , Roblero J S
Published: August 2012

The specificity of antidiuretic actions of pepsanurin, a peptidic fraction obtained by pepsin hydrolysis of plasma, was studied in anesthetized rats and in isolated perfused rat kidneys. Pepsanurin was obtained from fresh dialyzed human plasma digested with pepsin (2,400 units/ml, 18 hours at 37 degrees C, pH 2.5), deproteinized (10 minutes at 80 degrees C), and centrifuged. In the rat, intraperitoneal injections of pepsanurin (0.5 ml/100 g body wt) significantly inhibited the effects of an intravenous bolus of atrial natriuretic peptide (ANP) (0.5 micrograms) on water, sodium, and potassium excretion without altering systemic blood pressure. In addition, pepsanurin abolished the peak in glomerular filtration rate and reduced the ANP-induced rise in fractional sodium excretion. Pepsanurin also inhibited the natriuretic effects of amiloride (10 micrograms/100 g body wt i.v.) without changing glomerular filtration rate, but it did not inhibit the potassium-retaining effect of amiloride. In contrast, pepsanurin had no effect on basal urinary excretion, and it did not affect the diuretic response induced by furosemide (doses of 25, 50, or 100 micrograms i.v.). Control peptidic hydrolysates prepared from human plasma preincubated 48 hours at 37 degrees C (PIPH), bovine albumin (BSAH), or human albumin did not inhibit ANP, amiloride, or furosemide. In perfused kidneys, pepsanurin significantly and reversibly reduced sodium and water excretion. Furthermore, pepsanurin, but not PIPH or BSAH, blocked the natriuretic and diuretic effects of ANP. These results support the existence of a specific plasma substrate able to release a peptide or peptides that counteract distal tubule diuresis and natriuresis by an intrarenal mechanism.
Bayesian analysis supports use of ambulatory blood pressure monitors for screening.
Authors: Elijovich F , Laffer C L
Published: August 2012

To assess whether there is a role for ambulatory blood pressure monitoring (ABPM) in screening for hypertension, we conducted Bayesian analysis of office blood pressure (OBP) as a diagnostic "test" in populations with different prior probabilities (PP) of hypertension. OBP was considered a positive test if systolic blood pressure was greater than 140 mm Hg or diastolic pressure was greater than 90 mm Hg. Chosen daytime ABPM cutoffs for a "gold standard" diagnosis of hypertension were systolic pressure of 139 and diastolic pressure of 88 mm Hg. Sensitivity and specificity of OBP were determined in 72 patients with established hypertension (PP = 1). After 3 weeks off therapy, OBP was 168 +/- 3/101 +/- 1 and ABPM was 151 +/- 2/94 +/- 1 mm Hg. Systolic ABPM was in the normotensive range in 17 patients and diastolic in 15 patients. OBP was falsely positive in 14 and 15 of these patients, respectively. Thus, sensitivity and specificity of OBP were 0.8909 and 0.1765 (systolic) and 0.9825 and 0 (diastolic). These data cannot be extrapolated to populations with lower PPs for use of Bayes' theorem. Hence, we calculated sensitivity and specificity for PP = 0 from published series of ABPM in normotensive subjects and used our measurements and these calculations in arithmetic interpolations for populations with PP 0.1-0.9. Sigmoid relations between PP and predictability of hypertension by a positive OBP were disclosed by use of Bayes' theorem. Their best-fit cubic polynomials predict that an elevated OBP will misdiagnose hypertension 46-50% of the time in a general population (PP = 0.2) but only 8-9% in a specialty practice (PP = 0.9).(ABSTRACT TRUNCATED AT 250 WORDS)
Possible role of the vascular renin-angiotensin system in hypertension and vascular hypertrophy.
Authors: Morishita R , Higaki J , Miyazaki M , Ogihara T
Published: August 2012

To investigate the vascular renin-angiotensin system in two-kidney, one clip (2K1C) hypertension, we measured angiotensinogen messenger RNA (mRNA) in the aorta and aortic and plasma angiotensin II (Ang II) concentration in 2K1C rats during early (4 weeks) and chronic (16 weeks) phases. Four weeks after clipping, there was no significant change in aortic angiotensinogen mRNA in both groups. However, the levels of plasma and aortic Ang II in 2K1C rats were significantly elevated compared with levels in control rats (p less than 0.05). Sixteen weeks after clipping, aortic angiotensinogen mRNA in 2K1C rats did not differ compared with the level in control rats. The aortic Ang II level in 2K1C rats was significantly increased compared with that in control rats (p less than 0.05), whereas there was no significant difference in the plasma Ang II level between the groups during this chronic phase. During both phases, morphological studies in 2K1C rats showed arteriosclerotic changes, with a significant increase in the wall-to-lumen ratio (p less than 0.01). The present study is the first to demonstrate an increase in vascular Ang II levels and concomitant morphological arteriosclerotic changes during both the early and chronic phases in 2K1C rats. Together with the results of our previous study that demonstrated an elevation of vascular renin activity during the early phase and increased vascular angiotensin converting enzyme activity during the chronic phase, we conclude that the elevated vascular renin activity and vascular angiotensin converting enzyme activity during each phase may play a dominant role in the increase in vascular Ang II observed during both phases.
Dormont High School (Pittsburgh, Pennsylvania) blood pressure study.
Authors: Kuller L H , Crook M , Almes M J , Detre K , Reese G , Rutan G
Published: August 2012

A cohort of high school students examined in a school health study between 1957-63 were followed to 1977, when as adults still living in the area, 373 (71%) were reexamined. Mean age at 17-year follow-up was 34 years. The mean systolic blood pressure (SBP) at follow-up for men was 125 mm Hg, women 111 mm Hg. The boys' SBP had increased 4.0 Hg while the girls' declined 4.0 mm Hg in 17 years. The boys had gained an average of 37.2 lbs, and 1 inch, the girls 16.7 lbs, and 0.5 inch. Tracking was studied in several ways. The correlation coefficient of the SBP taken 17 years apart ws 0.44 for boys and 0.39 for girls. Current SBP was 115 mm Hg for boys with the lowest tenth of high school SBPs and 131 mm Hg for the boys in the highest tenth. Thirty-nine had hypertension, DBP greater than or equal to 90, or were on antihypertensive medication. They had had substantially higher SBP and weight in high school, and had gained more weight from high school to adult life than controls. After adjusting for high school SBP, weight gain for boys was the major determinant of subsequent high blood pressure (BP).
The Minneapolis childrn's blood pressure study. Part 2: multiple determinants of children's blood pressure.
Authors: Prineas R J , Gillum R F , Horibe H , Hannan P J
Published: August 2012

Among 9977 public school children aged 6 to 9 years screened in late winter and spring of 1978 in Minnesota, systolic blood pressure (SBP) and diastolic fourth phase blood pressure (DBP4) were found to be unrelated to age when height and body mass index (kg/m2) were taken into account. Weight was the best single measure of body size for predicing blood pressure. Black and white children had small and inconsistent, although statistically significant, differences in blood pressure after adjusting for other variables. The same was true for boys and girls. The problems of establishing normal blood pressures for children are discussed. The current analyses suggest the use of blood pressure centiles by height.
Behavioral response to induced conflict in families with a hypertensive father.
Authors: Baer P E , Vincent J P , Williams B J , Bourianoff G G , Bartlett P C
Published: August 2012

To clarify the possible environmental mediation of familial aggregation of blood pressure (BP), we examined whether the behavior of family members differed between families with a hypertensive (n = 16) or a normotensive (n = 15) father. Three-member families consisting of a father, mother, and a boy or girl aged 8-13 years were videotaped as they interacted under standard conditions calling for disagreement or conflict. Their BPs were recorded before and after interactions. The videotaped material was reliably coded into behavioral categories by independent observers. The aggregate of all three members of families with hypertensive fathers, as well as normotensive mothers and the children in these families, showed significantly more negative nonverbal behavior than their counterparts in families with normotensive fathers.
Obesity, sodium intake, and blood pressure in adolescents.
Authors: Ellison R C , Sosenko J M , Harper G P , Gibbons L , Pratter F E , Miettinen O S
Published: August 2012

It has been postulated that increased dietary sodium associated with greater food intake by obese people is a mechanism for the relationship between obesity and blood pressure (BP). We have evaluated this hypothesis by exploring the interrelationships of measures of obesity, sodium intake, and BP in 248 "normal" adolescents, 16 to 17 years of age. As an index of sodium intake, the sodium excretion in three overnight urine collections was used. As a more specific index of saltiness of diet, we used a ratio of sodium excretion to calorie intake, with calories estimated from 3-day diet records and dietary interview. Body weight and other measures of obesity showed a positive relationship with systolic blood pressure (SBP), but not with diastolic (K5) blood pressure (DBP5). Measures of overnight sodium excretion were positively correlated with body weight and calculated body fat percentage, suggesting that heavier people indeed ingest more sodium. This may result not from increased intake of food per se, but from increased saltiness of diet, since calorie intake did not increase with body weight. No significant relationships were found between BP and concurrent measures of sodium excretion or diet saltiness.
Blood pressure, electrolytes, and body size: their relationships in young relatives of men with essential hypertension.
Authors: Siervogel R M , Frey M A , Kezdi P , Roche A F , Stanley E L
Published: August 2012

In 154 white chldren aged 8 to 18 years from four large kindreds, relationships among blood pressure (BP), age, sex, body size, and electrolyte excretion were studied. Each kindred was ascertained through one male aged 35-58 years with essential hypertension, namely, a diastolic blood pressure (DBP) over 95 mm Hg. Weight, relative weight (relative to NCHS median for age, sex, and stature), subcutaneous fatfolds, various indices of obesity, and other measures of body size were significantly correlated with systolic blood pressure (SBP) and DBP in each sex (r = 0.3 to 0.7). Sodium and potassium excretion in 24-hour urine was also positively correlated with some measures of body size, and tended to increase with body size at a slightly more rapid rate in boys than in girls. In addition, there was a strong correlation between electrolyte excretion and BP in boys (r = 0.2 to 0.6); however, when the effects of age, body size and fatness were statistically removed, the correlations between BP and electrolyte excretion were not significant, except for 4th phase diastolic pressure (DBP4). These data, therefore, while not strongly supporting a relationship between sodium excretion and BP in children, do not rule out such a relationship, especially in families with a history of hypertension. In addition, these data provide further evidence of a very strong association between BP and body size and fatness in boys and girls.
Insulin levels are similar in obese salt-sensitive and salt-resistant hypertensive subjects.
Authors: Egan B M , Stepniakowski K , Nazzaro P
Published: August 2012

Evidence supports the hypothesis that hyperinsulinemia, especially in obesity, contributes to salt-sensitive hypertension by enhancing sodium retention and blunting the normal reduction of sympathetic drive and vascular resistance that occurs during a high versus low NaCl diet. To address these issues, we studied 18 obese (body mass index, > 27 kg/m2) subjects younger than 45 years old with mild hypertension to determine if the salt-sensitive versus salt-resistant subset had higher insulin levels, retained more volume, and failed to suppress sympathetic drive and vascular tone normally on a high (approximately 200 mEq/d) versus low (20 mEq/d) NaCl diet for 7 days each. Six obese subjects were salt sensitive, with an 8.4 +/- 2.1 (SEM) mm Hg increase of ambulatory mean blood pressure on the high versus low NaCl diet. Ten obese subjects were salt resistant, with a 7.1 +/- 0.9 mm Hg reduction of ambulatory mean blood pressure on high versus low NaCl. The salt-sensitive and salt-resistant groups had similar values, respectively, for the insulin area under the curve during an oral glucose tolerance test on low (14.6 +/- 1.8 versus 14.0 +/- 1.4 mU x min/dL, P = NS) and high (10.6 +/- 1.5 versus 10.6 +/- 1.0, P = NS) salt diets. Although insulin levels were similar, insulin raised calf blood flow in salt-resistant subjects (P < .05) but not in salt-sensitive subjects on the high NaCl diet.(ABSTRACT TRUNCATED AT 250 WORDS)
Participation of ouabainlike compound in reduced renal mass-saline hypertension.
Authors: Yamada K , Goto A , Nagoshi H , Hui C , Yagi N , Sasabe M , Omata M
Published: August 2012

We examined the role of ouabainlike compound in reduced renal mass-saline hypertension using a population of rats immunized with ouabain. To develop ouabain-immunized rats, ouabain-bovine serum albumin conjugates were injected subcutaneously three times at 4-week intervals. Titer determinations were made 2 weeks after the third immunization, and rats with high titers were used in the study. Immunoglobulin G fractions from ouabain-immunized rats effectively inhibited the contractile response of guinea pig aorta to exogenous ouabain (150 nmol). Fourteen ouabain-immunized and seven nonimmunized control rats underwent subtotal nephrectomy. An additional eight ouabain-immunized and six nonimmunized rats served as sham-operated rats. Four groups of rats drank 1% NaCl solution for 3 weeks, and systolic blood pressure was measured weekly by the tail-cuff method. Two groups of sham-operated rats remained normotensive. In contrast, two groups of subtotally nephrectomized rats developed hypertension. However, among these rats, systolic blood pressure was significantly lower in ouabain-immunized rats than in nonimmunized rats (161 +/- 5 versus 180 +/- 3 [+/- SEM) mm Hg, P < .01). The decrease in blood pressure was accompanied by a significant inhibition of aortic hypertrophy (P < .05). These results indicate that chronic blockade of circulating ouabainlike compound partly ameliorates reduced renal mass-saline hypertension and suggest that circulating ouabainlike compound may be involved in the pathophysiology in this model of hypertension.
Angiotensinogen: an acute-phase protein?
Authors: Soden M , Klett C , Hasmann T , Hackenthal E
Published: August 2012

Angiotensinogen has been assumed to be an acute-phase protein, because some forms of acute inflammation, eg, the injection of lipopolysaccharide or cellite or partial hepatectomy, increased the hepatic synthesis of angiotensinogen. In addition, the well-characterized nephrectomy-induced stimulation of angiotensinogen was thought to represent an acute-phase reaction. To evaluate this hypothesis, we examined changes in angiotensinogen secretion by the isolated perfused rat liver after the systemic administration of turpentine or lipopolysaccharide as well as in response to nephrectomy or sham nephrectomy. Comparison was made with the secretion of two typical acute-phase proteins, alpha 1-acid glycoprotein and alpha 2-macroglobulin, and with the secretion of the negative acute-phase protein albumin. All forms of experimental surgery stimulated the secretion of both control acute-phase proteins several-fold. In contrast, the response of angiotensinogen was not uniform; lipopolysaccharide and bilateral nephrectomy stimulated secretion twofold to threefold, sham nephrectomy had no effect, and turpentine decreased the secretion to 30% of the control level. A similar inhomogeneity was found in an additional experiment performed to analyze the direct effects of interleukin-1 or interleukin-6 on the secretion of angiotensinogen by freshly isolated hepatocytes. Interleukin-6 increased but interleukin-1 decreased the mRNA and secretion of angiotensinogen, whereas both cytokines increased the secretion of both acute-phase proteins. Because of this nonuniform behavior of angiotensinogen, it is premature to classify angiotensinogen as an acute-phase protein until a specific function for angiotensinogen during acute inflammation is known.
Regulation of angiotensin II receptors in rat brain during dietary sodium changes.
Authors: Sandberg K , Ji H , Catt K J
Published: August 2012

Activation of the renin-angiotensin system by sodium deficiency is associated with reciprocal changes in the expression of angiotensin II receptors in adrenal glomerulosa and vascular smooth muscle cells. The effects of dietary sodium changes on the expression of brain angiotensin receptor subtype 1 (AT1) mRNAs were examined in rats maintained on normal, low, and high sodium intake for 3 weeks. Plasma aldosterone and renin activity were elevated in rats maintained on a low salt diet compared with normal rats and were reduced in rats maintained on a high salt diet. These results are consistent with previous findings on the effects of altered dietary sodium on the renin-angiotensin system. The expression of AT1A and AT1B receptor subtype mRNAs was determined by quantitative reverse transcriptase-polymerase chain reaction during changes in sodium intake. The results revealed that sodium deprivation enhanced the expression of AT1B receptors in decorticated brains by 164% compared with high sodium intake. Conversely, high sodium diet increased the expression of AT1A receptors by 155% in the brain compared with low sodium intake. These data suggest that AT1A and AT1B receptors play reciprocal roles in central mechanisms for the control of fluid homeostasis. Further analysis of the molecular biology of angiotensin II receptor regulation in the brain may provide new insights into the interplay between the renin-angiotensin system and blood pressure regulation and also into the role of angiotensin II in the pathogenesis of essential hypertension.
Chronic hyperinsulinemia augments deoxycorticosterone acetate-salt hypertension.
Authors: Kitamura S , Seto S , Nagao S , Matsuo K , Akahoshi M , Yano K
Published: August 2012

To evaluate the effect of chronic hyperinsulinemia on blood pressure in salt-dependent hypertension, we infused insulin (1.0 IU/d, n = 15) or saline (n = 13) for 4 weeks into deoxycorticosterone acetate-salt hypertensive rats. The insulin infusion increased plasma insulin levels to 24 +/- 2 microU/mL, which was higher than in the saline-infused rats (9 +/- 1 microU/mL) but was still within the physiological range. Blood pressure was measured by the tail-cuff method twice a week, and daily sodium intake and urinary sodium excretion were calculated for 3 weeks. At week 4, arterial pressor responsiveness to norepinephrine, angiotensin II, and hexamethonium bromide was evaluated. After 14 days of chronic infusion, the insulin group showed a higher blood pressure than the saline group (on 21st day: 178 +/- 6 versus 156 +/- 5 mm Hg, P < .05 by tail-cuff method; 171 +/- 4 versus 149 +/- 3 mm Hg, P < .05 by direct intra-arterial measurement). This blood pressure difference was eliminated after ganglionic blockade with hexamethonium bromide (86 +/- 4 mm Hg in insulin-treated and 89 +/- 4 mm Hg in saline-treated rats by direct intra-arterial measurement). Throughout the experiment, neither sodium balance nor arterial pressor responsiveness to norepinephrine or angiotensin II differed between the two groups. In conclusion, chronic hyperinsulinemia in the physiological range augments the development of hypertension in salt-dependent hypertension, and this augmentation may be mediated by sympathetic stimulation independent of salt retention.
Three-dimensional echocardiography. Advances for measurement of ventricular volume and mass.
Authors: King D L , Gopal A S , Keller A M , Sapin P M , Schröder K M
Published: August 2012

There is a need for more accurate and reproducible serial measurement of left ventricular volume and mass in individual subjects by echocardiography. Conventional echocardiography has significant measurement variability because of its use of geometric assumptions and image plane positioning errors. Guided three-dimensional echocardiography eliminates geometric assumptions and reduces image plane positioning errors by using a "line of intersection" display. Use of three-dimensional guided imaging for a one-dimensional measurement of the left ventricle resulted in a threefold improvement of interobserver variability over conventional echocardiographic measurements. Computer-aided three-dimensional reconstruction of the ventricle for ventricular volume from a series of 8 to 10 short-axis images also achieved more than a threefold improvement of interobserver variability compared with two-dimensional echocardiography. Three-dimensional echocardiographic computation of ventricular volume and mass in healthy subjects was achieved with an accuracy comparable to magnetic resonance imaging and was superior to two-dimensional echocardiography. Three-dimensional echocardiography promises to be a more accurate method of estimating left ventricular volume and mass and may be suitable for serial study of individual subjects because of its improved accuracy and decreased interobserver variability compared with conventional echocardiographic methods.
Cardiovascular effects of brain kinin receptor blockade in spontaneously hypertensive rats.
Authors: Madeddu P , Glorioso N , Varoni M V , Demontis M P , Fattaccio M C , Anania V
Published: August 2012

We studied the role of brain kinins in the regulation of cardiovascular function. Intracerebroventricular injection of 380 pmol bradykinin increased mean blood pressure by 20 +/- 2 mm Hg (P < .01) in normotensive Wistar-Kyoto (WKY) rats. Complete inhibition of this effect was achieved with intracerebroventricular administration of the newly synthesized, long-acting B2 receptor antagonist D-Arg,[Hyp3,Thi5,D-Tic7,Oic8]-bradykinin (Hoe 140). On a molar basis, Hoe 140 was two orders of magnitude more potent than antagonists of the first generation. Baroreceptor sensitivity, estimated as the heart rate response to blood pressure changes induced by intravenous injection of phenylephrine or sodium nitroprusside, was not altered by Hoe 140 in WKY rats. In spontaneously hypertensive rats (SHR), baroreceptor reflex sensitivity to increments in mean blood pressure was reduced by Hoe 140 (mean slope value: -0.47 +/- 0.07 versus -0.92 +/- 0.13 beats per minute per millimeter of mercury in controls, P < .05). Hoe 140 did not affect the tachycardic component of the baroreceptor reflex. Two-week intracerebroventricular infusion of Hoe 140 did not alter systolic blood pressure or heart rate in WKY rats. In SHR, systolic blood pressure increased (P < .01) similarly during the infusion of Hoe 140 or vehicle (from 174 +/- 6 to 220 +/- 5 mm Hg and 178 +/- 4 to 210 +/- 4 mm Hg at 2 weeks, respectively), whereas heart rate did not change.(ABSTRACT TRUNCATED AT 250 WORDS)
Salt-regulating hormones in young normotensive obese subjects. Effects of saline load.
Authors: Licata G , Volpe M , Scaglione R , Rubattu S
Published: August 2012

To investigate whether the response of salt-regulating hormones to volume expansion is impaired in obese subjects, we assessed the effects of saline load (0.25 mL/kg.min.120 min) in 9 young, healthy, normotensive obese subjects (body mass index, > 30 kg/m2) and in 10 lean control subjects (body mass index, < 25 kg/m2) matched for age, gender, height, and mean blood pressure. Hematocrit, plasma renin activity (PRA), plasma aldosterone (PA), atrial natriuretic factor (ANF), and urinary sodium excretion (UNaV) were evaluated. Saline load increased ANF levels significantly (P < .001) in lean subjects at both 60 and 120 minutes, whereas they decreased in obese subjects. Such decreases became significant (P < .01) at 120 minutes. Suppression of PRA and PA by saline load were more marked in lean than obese subjects. Hematocrit decreased in both groups, and UNaV increased more in lean than obese subjects during saline load. Comparisons of percent changes in ANF, PRA, and PA after saline load showed that the responses of lean and obese subjects were significantly different (P < .001 for ANF at both 60 and 120 minutes; P < .05 for PRA and PA at both 60 and 120 minutes). In conclusion, the lack of ANF response and the reduced suppression of PRA and PA to saline load indicate a dysfunction of these systems in obese subjects. This alteration may be involved in the higher susceptibility of obese subjects to developing hypertension.
Timing for administration of an antihypertensive drug in the treatment of essential hypertension.
Authors: Umeda T , Naomi S , Iwaoka T , Inoue J , Sasaki M , Ideguchi Y , Sato T
Published: August 2012

To find the best timing for administration of long-acting antihypertensive drugs, we gave nitrendipine, a calcium antagonist of the dihydropyridine group, once a day to six hospitalized and drug-free patients with essential hypertension, changing the time of administration and studying the effects on the circadian rhythm of blood pressure. After control values of 24-hour blood pressure variations were taken with patients on placebo, a 10-mg tablet of nitrendipine was given for 3 days on three occasions--at 6 AM on awakening, at 8:30 AM after breakfast, and at 6 PM after supper; 24-hour blood pressure values for each period were recorded on the third day. The 24-hour blood pressure values during the control period showed a biphasic circadian rhythm, with higher values during wakefulness and lower values during sleep. The control period was also characterized by a rapid rise in blood pressure on awakening, the so-called morning surge of blood pressure, and a gradual decline during sleep at night. Although the morning surge was not completely suppressed by nitrendipine given after breakfast, it was diminished by the drug given on awakening or after supper; the latter brought a deeper decline in blood pressure during sleep compared with other times. The average of 24-hour blood pressure values obtained by nitrendipine given on awakening was the lowest among the three occasions. Thus, administration of long-acting calcium antagonists with a rapid onset of action on awakening in the early morning seems to be a more rational and beneficial alternative than the conventional administration after breakfast.(ABSTRACT TRUNCATED AT 250 WORDS)
Felodipine therapy may not alter glucose and lipid metabolism in hypertensives. Felodipine Multicenter Prospective Study Group in Japan.
Authors: Shionoiri H , Takizawa T , Ohyama Y , Ishii J , Katayama S , Nagasawa T , Kitamoto K , Nagasawa K , Hariya Y , Sato R
Published: August 2012

The effects of long-term monotherapy with felodipine, a calcium antagonist, on blood pressure, glucose tolerance, and serum lipid profiles were prospectively investigated in 51 hypertensive patients: 13 with normal glucose tolerance and 38 with glucose intolerance. The levels of plasma glucose, serum lipids, and glycosylated hemoglobin A1c were determined before and during long-term (7.5 +/- 0.5 months; range, 6 to 9 months) therapy with felodipine. A 75-g oral glucose tolerance test was performed before and during long-term felodipine therapy. Significant decreases in both systolic and diastolic blood pressures in both patient groups were maintained during the therapy. Neither fasting nor post-glucose load venous plasma glucose levels were altered in either group of patients, and no patients with normal glucose tolerance developed diabetes mellitus during the study. Serum lipid levels did not change significantly in either group of patients except for significant decreases in high-density lipoprotein cholesterol and apolipoprotein A-I in the group with normal glucose tolerance tests, but those changes remained within the normal range. Furthermore, neither serum lipid nor apolipoprotein levels were altered, even in patients with hypercholesterolemia (total cholesterol levels, > 5.69 mmol/L = 220 mg/dL). These results suggest that long-term therapy with felodipine may not alter glucose and lipid metabolism in hypertensive patients, and felodipine appears to be useful as an antihypertensive agent for hypertensive patients with either dyslipidemia or impaired glucose metabolism.
Renal response to amino acid infusion in essential hypertension.
Authors: Juncos L , Cornejo J C , Pamies-Andreu E , Romero J C
Published: August 2012

In the present study, we evaluated the renal response to a 4-hour infusion of amino acids in essential hypertensive patients, as well as the effects that dietary sodium restriction and enalapril (a converting enzyme inhibitor) had on this renal response. During normal sodium intake, amino acid infusion significantly increased renal plasma flow from 383 +/- 58 to 478 +/- 51 mL/min and glomerular filtration rate from 82 +/- 8 to 100 +/- 13 mL/min. All these effects were abolished when the patients received a low sodium diet (40 mmol/d) for 3 days before the amino acid infusion. The administration of enalapril to the patients during sodium restriction restored the amino acid-induced increment in renal plasma flow (from 388 +/- 35 to 573 +/- 48 mL/min) and glomerular filtration rate (from 88 +/- 9 to 103 +/- 10 mL/min). Mean arterial pressure remained unaltered under all experimental conditions. The results show that in patients with essential hypertension dietary sodium restriction prevents amino acid-induced increments in glomerular filtration rate and renal plasma flow and that this effect is restored during the simultaneous administration of enalapril.
Oxytocic effect of trypsin on the isolated rat uterus.
Authors: Orce G , Castillo G , Esteban S
Published: August 2012

To study the oxytocic effect of trypsin, we measured the force of isometric contraction in uteri isolated from estrogenized rats exposed to trypsin (8.8 x 10(-10) to 1.7 x 10(-6) mol/L) either alone or in the presence of receptor antagonists to angiotensin II [saralasin ([Sar1,Ala8]angiotensin II) or DuP 753 (losartan)] or to kinins (D-[Arg0,Hyp3,Thi5,8,D-Phe7]-bradykinin). We found that saralasin or DuP 753, but not the kinin antagonist, displaced the dose-response curve to the right. Exposure to exogenous angiotensin I desensitized the preparation to further doses of either angiotensin I or II or trypsin, without altering the effects of oxytocin or bradykinin. Enalaprilat (an angiotensin I converting enzyme inhibitor) or pepstatin A (a renin inhibitor) also displaced the dose-response curve to trypsin to the right, without altering the effects of oxytocin or angiotensin II. Our results indicate that the response to trypsin is mediated by an agent produced from a substrate present in the uterus and acting on the angiotensin II type 1 receptor and are consistent with both renin and angiotensin I converting enzyme being involved in its mechanism of action, thus supporting the notions that the renin-angiotensin system may be important in the late stages of pregnancy and that serine proteases existing in the uterus may contribute to its activation.
Familial hypertension and albuminuria in normotensive type I diabetic patients.
Authors: Freire M B , Ferreira S R , Vivolo M A , Oliveira J M , Zanella M T
Published: August 2012

An inherited predisposition to hypertension may increase susceptibility to nephropathy in type I diabetes. We evaluated the influence of a family history of essential hypertension on albuminuria in normotensive, normoalbuminuric type I diabetic patients. Forty-two diabetics (12.9 +/- 2.04 years) were divided into three groups according to tertiles of albumin excretion rate (group 1, 1.27 +/- 0.35; group 2, 2.43 +/- 0.49; group 3, 6.37 +/- 3.43 micrograms/min; P < .001). Familial hypertension was considered to be present if the patient had one parent or grandparent on antihypertensive therapy. The three groups did not differ concerning age, diabetes duration, insulin requirement, body mass index, blood pressure, and urinary glucose excretion. Albumin excretion rate did not correlate with any parameter studied. The frequency of hypertension was significantly lower among the relatives of the patients from group 1 compared with those from groups 2 and 3 (28.6% versus 64.3% versus 78.6%, P < .03). Our data suggest that a familial antecedent of hypertension in normoalbuminuric type I diabetic patients is associated with a high normal albumin excretion rate not related to increases in blood pressure. Early changes in renal hemodynamics, seen in patients with a predisposition to hypertension, may contribute to increments in albuminuria even within the normal range.
Nitric oxide participates in calcium-mediated regulation of renin release.
Authors: Beierwaltes W H
Published: August 2012

The regulation of renin release is unusual in that intracellular calcium reportedly acts as an inhibitory second messenger. Increased calcium not only inhibits renin release but is a cofactor in nitric oxide synthesis. Also, nitric oxide can inhibit renin release. This study was done in vitro using rat renal cortical slices to determine whether calcium-mediated renin inhibition could be in part due to the concurrent production of nitric oxide. Renin concentration in the incubation medium was determined by radioimmunoassay for angiotensin I (Ang I) generation (in nanograms Ang I per hour per milligram per 30 minutes of incubation). In all studies, n = 6 to 17. In normal-calcium incubation medium (2.6 mmol/L), 10(-4) mol/L NG-monomethyl L-arginine, which blocks nitric oxide synthesis, caused an 18% increase in basal renin release (78.6 +/- 8.9 versus 66.7 +/- 5.8 [ng Ang I/h]/mg per 30 minutes incubation, P < .05). When calcium was eliminated from the incubation medium, basal renin release doubled (to 133.1 +/- 15.2 [ng Ang I/h]/mg per 30 minutes incubation, P < .001). Without calcium, inhibiting nitric oxide synthesis had no further effect on renin release (126.8 +/- 17.7 [ng Ang I/h]/mg per 30 minutes incubation). High-calcium medium (7.8 mmol/L) reduced basal renin release by half (30.8 +/- 4.8 [ng Ang I/h]/mg per 30 minutes incubation, P < .001), but inhibiting nitric oxide synthesis in high-calcium medium stimulated renin release by 50% (46.9 +/- 6.2 [ng Ang I/h]/mg per 30 minutes incubation, P < .005). Addition of the calmodulin inhibitor W-7 completely reversed the inhibition of renin by high-calcium medium.(ABSTRACT TRUNCATED AT 250 WORDS)