bluuebunny/crossref_metadata_2025 huggingface dataset:
Correlates of adolescent blood pressure at five-year follow-up.
Authors: Kotchen J M , Kotchen T A , Guthrie G P , Cottrill C M , McKean H E
Published: August 2012

In 1973, standardized measurements of blood pressure (BP), height, and weight were obtained on all adolescents attending high school in a rural Kentucky county. In 1978, a 5-year follow-up BP study was undertaken of all adolescents who were 14-15 years old at the time of the initial survey (n = 310), and of selected 16-19 year olds who were in the high, intermediate, and low ranges of the initial sex-specific BP distributions (n = 198). Follow-up measurements included height, weight, and BP on all subjects and, in addition, overnight sodium (Na) excretion, serum cholesterol, glucose, triglyceride, and uric acid concentrations on the older group. Our findings indicate that BP in young adults is related to BP in adoleslcence, change in relative weight since adoleslcence, and current relative weight. Relative rank order of initial BP levels were maintained over the 5-year period in both the younger and older groups. Additional cardiovascular disease risk factors were found to cluster in young adults with high BP, and clustering of risk factors may, in part, be related to high relative weight.
Prepregnant blood pressure, hypertension during pregnancy, and later blood pressure of mothers and offspring.
Authors: Langford H G , Watson R L
Published: August 2012

In a community-based prospective study of black women, blood pressure (BP) before the onset of the first pregnancy was significantly higher in participants who were eventually diagnosed as having pre-eclampsia than those not so diagnosed. The diagnosis of "pre-eclampsia" appeared to be based entirely on BP; "hypertension associated with pregnancy" is probably a more accurate term. The BP of the pre-eclamptic group was consistently higher before admission to h ospital, during hospitalization, and at 6 weeks and 9 years after delivery. Daughters of pre-eclamptic mothers had higher BP than those of non-pre-eclamptic mothers; this difference was not apparent in boys. The data are compatible with a sex-limited subset of essential hypertension. It is perhaps estrogen-dependent, manifesting itself as mild "pre-eclampsia" in the mother and mild BP elevation in female offspring.
Urinary electrolytes, body weight, and blood pressure. Pooled cross-sectional results among four groups of adolescent females.
Authors: Watson R L , Langford H G , Abernethy J , Barnes T Y , Watson M J
Published: August 2012

Results of blood pressures (BP) and urinary electrolyte excretion studies are reported among several groups of adolescent and young adult females, both black and white, who were initially examined in high school and restudied at home 3--4 years later. Pooling of the data from the several cross-sectional studies (n = 662) revealed a weak but statistically significant positive correlation systolic blood pressure (SBP) and the urinary sodium (Na) excretion rate. Three of four correlations between SBP and potassium (K) were of an inverse nature. Although not statistically significant in their own right, when coupled with the Na/K excretion ratio, which was significantly associated with SBP, a moderating role for K is suggested. The urinary Na, K, and creatinine (Cr) excretion rates were highly intercorrelated and were correlated with weight. As measured by R2 in a stepwise regression analysis, weight contributed approximately 3% to the BP variance, and the urinary electrolytes accounted for approximately 2% of the SBP variance. Statistically significant partial correlation coefficients between SBP and Na, and Na/K, remained after adjusting for body weight.
Factors affecting blood pressures in newborn infants.
Authors: Zinner S H , Lee Y H , Rosner B , Oh W , Kass E H
Published: August 2012

Blood pressure (BP) was measured in 837 newborn infants ranging in age from 1-6 days and their mothers in Boston, Massachusetts, and Providence, Rhode Island. The BP increased significantly with age in days, birth weight, weight on day of measurement, arm circumference, and ponderal index. There was no relation of sex, race, pulse rate, type of feeding, or Apgar scores to BP in the neonatal period. Significant correlation was found between maternal and infant BP (r = 0.196 for systolic (SBP) and 0.157 for diastolic (DBP) pressures, p < 0.001). Preliminary analysis shows a trend for resemblance of 1-month and newborn BP.
Chronic blood pressure effects of bufalin, a sodium-potassium ATPase inhibitor, in rats.
Authors: Pamnani M B , Chen S , Yuan C M , Haddy F J
Published: August 2012

Endogenous Na+,K(+)-ATPase inhibitors may have a role in the mechanism of low-renin hypertension. Two such compounds have been characterized: ouabain from human plasma and resibufogenin from toad plasma. Previously, we examined the acute effects of ouabain and bufalin (which has the same structure as resibufogenin except for one H+) in normal rats. Bufalin raised blood pressure, but ouabain had little effect. In contrast, given chronically, ouabain substantially increased blood pressure in normal rats and 70% reduced renal mass rats on a salt-free diet. We have now examined the chronic effects of bufalin in rats. Normal rats received 14.8 micrograms/kg per day bufalin or an equimolar dose of ouabain intraperitoneally for 6 weeks; 70% reduced renal mass rats also received 14.8 micrograms/kg per day bufalin. Another group of normal rats received 29.6 micrograms/kg per day bufalin intraperitoneally for 6 weeks. Respective control animals received vehicle. In contrast to ouabain, blood pressure did not increase in normal rats receiving the 14.8 micrograms dose of bufalin. However, normal rats receiving 29.6 micrograms bufalin and 70% reduced renal mass rats receiving 14.8 micrograms bufalin developed significant increases in blood pressure. Increases in blood pressure were associated with decreases in myocardial Na+,K(+)-ATPase activity and correlated with increased plasma Na+,K(+)-ATPase inhibitory activity. Thus, although bufalin is a more potent pressor agent than ouabain when both agents are given acutely, ouabain is at least as potent a vasopressor agent as bufalin when given chronically. Thus, both are pressor agents, more so in the presence of reduced renal mass, when given chronically in the rat.
Renal arteriolar angiotensin responses during varied adenosine receptor activation.
Authors: Carmines P K , Inscho E W
Published: August 2012

We performed experiments to test the hypothesis that endogenous adenosine acts as an essential cofactor required for eliciting angiotensin II (Ang II)-induced afferent and/or efferent arteriolar vasoconstriction. Enalaprilat (2 mg IV) was administered to anesthetized rats to reduce endogenous Ang II levels. Kidneys and blood were harvested from these animals and used for study of renal microvascular function using the in vitro blood-perfused juxtamedullary nephron technique. Arteriolar inside diameter was monitored videomicroscopically in (1) normal kidneys, (2) kidneys subjected to adenosine receptor blockade (100 mumol/L 1,3-dipropyl-8-p-sulfophenylxanthine), and (3) kidneys continuously exposed to 1 mumol/L adenosine. Under resting conditions, arteriolar diameters were similar in all three groups of kidneys, averaging 24.8 +/- 1.0 microns (n = 23) in afferent arterioles and 24.0 +/- 0.9 microns (n = 16) in efferent arterioles. In normal kidneys, adenosine (10 mumol/L) decreased both afferent (10.2 +/- 2.0%) and efferent (6.5 +/- 0.8%) diameters, an effect that was absent in kidneys subjected to adenosine receptor blockade. Ang II (10 pmol/L to 100 nmol/L) elicited dose-dependent vasoconstriction of both vascular segments in normal kidneys. At a concentration of 100 nmol/L, Ang II decreased afferent diameter by 36.8 +/- 8.5% and efferent diameter by 30.8 +/- 9.6%. Neither afferent nor efferent arteriolar Ang II dose-response relations were significantly different in kidneys treated with low-dose adenosine or the adenosine receptor blocker. These observations refute the hypothesis that a receptor-mediated action of adenosine is required for Ang II-induced constriction of juxtamedullary afferent or efferent arterioles.(ABSTRACT TRUNCATED AT 250 WORDS)
Stimulation of vascular glycosaminoglycan synthesis by subpressor angiotensin II in rats.
Authors: Simon G , Abraham G , Altman S
Published: August 2012

The vascular trophic effects of angiotensin II (Ang II) in small doses may precede its hypertension-producing effect, and de novo synthesis of components of extracellular matrix may be a requirement for Ang II-stimulated growth. In the present study, therefore, the incorporation of 35SO4 into glycosaminoglycans (synthesis) of aorta and bladder wall of young adult, male Sprague-Dawley rats was measured ex vivo after 48 hours of Ang II administration at two dose levels, 100 and 200 ng.kg-1.min-1 IP. Vehicle-infused rats served as controls. Compared with controls, systolic blood pressure was unchanged in rats receiving 100 ng.kg-1.min-1 Ang II and rose by 13 mm Hg (P < .05) in rats receiving the 200-ng.kg-1.min-1 dose. In Ang II-treated rats, glycosaminoglycan synthesis of the aorta was increased by 20% (P < .05) and 52% (P < .005) at the two dose levels, respectively. Glycosaminoglycan synthesis of bladder smooth muscle was also increased in Ang II-treated rats (P < .01), but the response was not dose dependent. By 7 to 10 days of Ang II administration (200 ng.kg-1.min-1), glycosaminoglycan synthesis of aorta returned toward baseline (P < .10, > .05). The rate of synthesis of subtypes of glycosaminoglycans in the aorta was proportionately increased by Ang II. The early occurrence, magnitude, and arterial pressure independence of Ang II-induced glycosaminoglycan synthesis suggest that restructuring of extracellular matrix may play an important role in both the trophic and hypertension-producing action of Ang II.
Consistency of ethnic differences in children's pressor reactivity. 1987 to 1992.
Authors: Murphy J K , Alpert B S , Walker S S
Published: August 2012

In this prospective investigation, all children enrolled in the public third-grade classrooms of an entire county (n = 474) had blood pressure measured both at rest and during a stressful television video game. Examinations were repeated in 4 subsequent years when cohort children as well as newly enrolled children were in grades 4, 5, 7, and 8. Both cross-sectional and longitudinal analyses indicated that black children demonstrated significantly greater systolic and diastolic pressor reactivity than white children. These data suggest that ethnic differences in children's pressor reactivity presage ethnic differences in adulthood hypertension.
Effect of lisinopril and metoprolol on arterial distensibility.
Authors: Barenbrock M , Spieker C , Hoeks A P , Zidek W , Rahn K H
Published: August 2012

Apart from lowering blood pressure, antihypertensive drugs may influence vessel wall function. In a randomized double-blind study, the effect of lisinopril and metoprolol on arterial distensibility was studied in 40 patients with essential hypertension. After a placebo run-in period, the patients were randomly treated with metoprolol (50, 100, or 200 mg) or lisinopril (5, 10, or 20 mg) for 10 weeks. In the lisinopril group, blood pressure decreased after 10 weeks of therapy from 173 +/- 10/102 +/- 5 to 155 +/- 10/85 +/- 3 mm Hg and in the metoprolol group from 167 +/- 12/102 +/- 4 to 153 +/- 8/84 +/- 3 mm Hg. Diameter (millimeters), relative change in diameter (percent), and distensibility (10(-3)/kPa) of the left common carotid artery were determined after the placebo run-in period and after 6 and 10 weeks of antihypertensive therapy. A multigate Doppler system was used to measure the vessel wall movements by Doppler analysis in M-mode; blood pressure was recorded by finger plethysmography (Finapres). Neither lisinopril nor metoprolol influenced the end-diastolic diameter of the common carotid artery after 6 and 10 weeks of treatment. In the lisinopril group, a significant increase of percent change in diameter (P < .05 compared with the baseline value; P < .05 compared with the metoprolol group) and distensibility (P < .01 compared with the baseline value; P < .05 compared with the metoprolol group) was observed. The results show that lisinopril but not metoprolol improves arterial distensibility in essential hypertension. Pressure-independent effects of angiotensin converting enzyme inhibitors may be important modulators of adaptive changes in the arterial wall.
Myocardial scintigraphic characteristics in patients with primary aldosteronism.
Authors: Abe M , Hamada M , Matsuoka H , Shigematsu Y , Sumimoto T , Hiwada K
Published: August 2012

To evaluate the difference in myocardial damage between primary aldosteronism and untreated essential hypertension, we performed thallium-201 myocardial single-photon emission computed tomography in 10 patients with primary aldosteronism and 10 patients with essential hypertension who were matched for age, sex, blood pressure, and the severity of left ventricular hypertrophy for primary aldosteronism. From the analysis of thallium-201 myocardial scintigraphy, extent score was calculated. Extent score was significantly higher in primary aldosteronism than in essential hypertension (45.8 +/- 23.5% versus 9.5 +/- 7.3%, P < .01). After operation, blood pressure significantly decreased, and the precordial voltages (SV1 + RV5) and left ventricular mass indexes were significantly reduced in patients with primary aldosteronism. Extent score was also significantly improved. These results suggest that despite the same severity of myocardial hypertrophy between primary aldosteronism and essential hypertension, the myocardial damage estimated by thallium-201 myocardial scintigraphy is more severe in primary aldosteronism than in essential hypertension. Extent score was useful for evaluation of the severity of myocardial damage in hypertensive patients.
Effects of chlorthalidone on ventricular hypertrophy in deoxycorticosterone acetate-salt hypertensive rats.
Authors: Cabral A M , Carvalhinho F B , Vasquez E C , Cicilini M A
Published: August 2012

Diuretics have been the mainstay of long-term treatment of hypertension, but there is no evidence suggesting that diuretics may be effective in reducing cardiac hypertrophy associated with hypertension. Thus, the present study was carried out to elucidate if long-term treatment with chlorthalidone (8 mg per animal per day added to food) affects the development of and reverses the ventricular hypertrophy in deoxycorticosterone acetate (DOCA) (8 mg/kg SC twice a week)-salt hypertensive rats. Chlorthalidone was given to one group during all 20 days of DOCA administration (preventive regimen) and to another group 20 days after DOCA treatment was initiated until the 40th day (therapeutic regimen). Chlorthalidone was found to reduce or prevent the development of ventricular hypertrophy, as assessed by a reduction in ventricular mass and cardiac protein as well as arterial hypertension. Both chlorthalidone regimens prevented the increase or induced a significant decrease in the plasma concentration of sodium and in cardiac sympathetic tone, which were both increased in DOCA-salt-treated rats. These data provide evidence that long-term chlorthalidone treatment is effective in preventing or reducing ventricular hypertrophy along with arterial hypertension. However, whether this is due to a reduction in plasma sodium or other additional mechanisms, such as a reduction in cardiac sympathetic tone, remains to be determined.
Increased cytosolic sodium and reduced Na,K-ATPase activity in transgenic rats.
Authors: Tepel M , Theilmeier G , Bachmann J , Barenbrock M , Spieker C , Ganten D , Rahn K H , Zidek W
Published: August 2012

The transgenic rat TGR(mRen2)27 is a new monogenetic model in hypertension research that develops fulminant hypertension after the mouse Ren-2d renin gene has been integrated into its genome. To evaluate the molecular mechanism of development of hypertension in this animal model, we measured cytosolic free sodium concentration in intact lymphocytes from seven transgenic rats and eight age-matched normotensive Sprague-Dawley rats using the novel sodium-sensitive fluorescent dye sodium-binding benzofuranisophthalate. Resting cytosolic sodium was significantly higher in transgenic rats compared with Sprague-Dawley rats (31.7 +/- 2.2 versus 18.2 +/- 0.4 mmol/L, mean +/- SEM, P < .001). Inhibition of Na,K-ATPase by 0.5 mmol/L ouabain for 5 minutes significantly increased lymphocytic cytosolic sodium in Sprague-Dawley rats to 36.5 +/- 3.4 mmol/L (P < .001 compared with resting value), whereas no significant change could be observed in transgenic rats (35.4 +/- 0.6 mmol/L), indicating that Na,K-ATPase is less responsive in transgenic rats. The Na,K-ATPase activity from erythrocytes was measured with an enzyme-linked assay. Na,K-ATPase activity was significantly reduced in transgenic rats compared with Sprague-Dawley rats (4.0 +/- 0.3 versus 8.1 +/- 0.6 U/L, P < .001). We concluded that reduced Na,K-ATPase activity leads to elevated cytosolic sodium in this model of genetic hypertension.
Association analysis of restriction fragment length polymorphism for alpha 2-adrenergic receptor genes in essential hypertension in Japan.
Authors: Umemura S , Hirawa N , Iwamoto T , Yamaguchi S , Toya Y , Kobayashi S , Takasaki I , Yasuda G , Tamura K , Ishii M
Published: August 2012

Recently, restriction fragment length polymorphism (RFLP) of alpha 2-adrenergic receptor gene (alpha 2-C10) digested with Bsu36I restriction enzyme has been reported in US populations. Therefore, we examined the association of this RFLP with essential hypertension by comparing the frequency of specific alleles for this gene in Japanese populations. The distribution of this RFLP was compared with that in US populations. Subjects were hypertensive patients with a family history of essential hypertension (n = 56) and normotensive subjects whose parents had no history of essential hypertension (n = 46). DNA was prepared from leukocytes. RFLP was determined by use of Southern blot analysis with an alpha 2-C10 probe and Bsu36I. The frequencies of the major (12-kb) and minor (5.8-kb) alleles were 0.30 and 0.70 in hypertensive patients and 0.38 and 0.62 in normotensive subjects, respectively. The difference between observed alleles in all subjects in each group was not significant (chi 2 = 1.33, P > .1). The difference between the overall allelic frequency in Japan and that reported in US populations was significant. This study found no evidence for an association between alpha 2-adrenergic receptor gene/Bsu36I RFLP and essential hypertension in Japan. However, the findings showed that the allele frequency in Japan differed from that reported in US populations.
Combined versus single effect of fosinopril and hydrochlorothiazide in hypertensive patients.
Authors: Fernández M , Madero R , González D , Camacho P , Villalpando J , Arriaga J
Published: August 2012

The antihypertensive effect and safety of fosinopril and hydrochlorothiazide combined were compared with each drug singly and placebo in a controlled manner. After a 4- to 5-week placebo lead-in period, 67 mild to moderate essential hypertensive patients (seated diastolic blood pressure > or = 95 and < or = 110 mm Hg) were randomized in a double-blind fashion into four parallel treatment groups: 20 mg fosinopril plus 12.5 mg hydrochlorothiazide, 20 mg fosinopril, 12.5 mg hydrochlorothiazide, and placebo during 8 weeks. Patients were seen biweekly. Sitting diastolic blood pressure was the outcome variable defining therapeutic response. The efficacy of fosinopril plus hydrochlorothiazide as a combined therapy was superior to any single drug (P < .05) and placebo (P < .01) in the treatment of mild to moderate essential hypertension. Mean adjusted systolic/diastolic blood pressure decrements at week 8 were -18.8/-13.7, -12.9/-11.8, -8.5/-9.3, and -2.7/-6.9 mm Hg for the fosinopril plus hydrochlorothiazide, fosinopril, hydrochlorothiazide, and placebo groups, respectively. Clinical adverse events and laboratory changes documented throughout the study were similar to placebo and were mild in severity in all groups.
Systemic and renal effects of nifedipine in cyclosporine-associated hypertension.
Authors: Textor S C , Schwartz L , Wilson D J , Wiesner R , Romero J C , Augustine J , Kos P , Hay E , Gores G , Dickson E R
Published: August 2012

Cyclosporine induces hypertension and wide-spread vasoconstriction after transplantation in addition to reducing kidney function. We studied hemodynamic, renal, and hormonal effects of monotherapy with nifedipine XL (n = 37) in liver transplant recipients within a year after transplant (median, 4.4 months). Systemic hemodynamics were determined with thoracic electrical bioimpedance. Blood pressure before therapy was 172 +/- 4/108 +/- 2 mm Hg. Sixty-four percent of recipients achieved blood pressures less than 140/90 mm Hg mediated by a fall in systemic vascular resistance index (2427 +/- 245 dyne.s.cm-5.m-2 in responders versus 2905 +/- 281 in nonresponders, P < .01). Despite the fall in systemic vascular resistance, glomerular filtration rates were not changed during nifedipine therapy, as measured by both creatinine and iothalamate clearances. Urinary prostacyclin (6-ketoprostaglandin F1 alpha) was suppressed below normal from 2468 +/- 323 ng/d before transplant to 1103 +/- 99 ng/d (P < .01) after transplant and did not change during nifedipine therapy. Urinary thromboxane B2 and plasma renin activity also fell after transplant and remained low during nifedipine. These data demonstrate that nifedipine can reverse systemic vasoconstriction associated with hypertension after transplantation. Systemic effects were not transmitted to the kidney sufficiently to improve glomerular filtration rate or reverse hormonal changes within the kidney. Hence, vascular and functional regulation of the kidney was dissociated from the systemic circulation during nifedipine administration after transplantation.
Role of hypertension in asymptomatic cerebral lacunae in the elderly.
Authors: Ikeda T , Gomi T , Kobayashi S , Tsuchiya H
Published: August 2012

To assess the role of hypertension in asymptomatic cerebral lacunae, we evaluated cranial computed tomography in 76 untreated hypertensive patients, 173 hypertensive patients treated with antihypertensive drugs, and 69 age-matched normotensive control subjects who were more than 60 years of age and without a history of stroke. Cerebral lacunae were diagnosed by computed tomography as a hypodense lesion less than 15 mm in diameter seen on a single 10-mm scan section. The factors contributing to lacunae were determined by stepwise discriminant analysis. Single or multiple cerebral lacunae were revealed in 27.6% (21 of 76) of untreated hypertensive patients, 17.3% (30 of 173) of treated hypertensive patients, and 7.2% (5 of 69) of normotensive control subjects. Incidence of lacunae was significantly higher in hypertensive patients than normotensive control subjects. Stepwise discriminant analysis showed that the most strongly contributing factor for lacunae was the grade of hypertensive retinopathy in untreated hypertensive patients and mean blood pressure in treated hypertensive patients. Asymptomatic cerebral lacunae were frequently detected by computed tomography in elderly patients with essential hypertension. The severity and duration of hypertension correlate positively with this type of vascular complication in hypertension.
Role of nitric oxide in the renin and heart rate responses to beta-adrenergic stimulation.
Authors: Reid I A , Bui H , Chou L
Published: August 2012

Studies in vitro and in vivo have implicated nitric oxide in the control of renin secretion. In the present study, the effect of inhibition of nitric oxide synthesis with NG-nitro-L-arginine methyl ester hydrochloride (L-NAME) on the renin secretory response to beta-adrenergic stimulation was investigated in conscious, chronically prepared rabbits. Intravenous infusion of isoproterenol at 0.02 microgram.kg-1 x min-1 for 30 minutes increased mean arterial pressure by 5 mm Hg (P < .05), heart rate by 51 beats per minute (P < .001), and plasma renin activity by 56% (P < .001). Intravenous infusion of L-NAME at 0.5 mg.kg-1 x min-1 increased mean arterial pressure by 6 mm Hg (P < .01) and decreased heart rate by 15 beats per minute (P < .01) and plasma renin activity by 31% (P < .05). L-NAME reduced the heart rate response to isoproterenol by 50% and inhibited the renin response. Infusion of isoproterenol at 0.05 microgram.kg-1 x min-1 did not change blood pressure but increased heart rate by 62 beats per minute (P < .001) and plasma renin activity by 283% (P < .001). Treatment with L-NAME again suppressed the heart rate response to isoproterenol and inhibited the renin response. Intravenous infusion of the nitric oxide donor nitroprusside at 2 micrograms.kg-1.min-1 in the presence of L-NAME decreased mean arterial pressure by 7 mm Hg (P < .05), increased heart rate by 14 beats per minute (P < .05), but did not change plasma renin activity. Nitroprusside fully restored the heart rate response to isoproterenol and partially restored the renin response.(ABSTRACT TRUNCATED AT 250 WORDS)
Chronic converting enzyme inhibition facilitates baroreceptor resetting to hypertensive levels.
Authors: da Silva V J , da Silva S V , Salgado M C , Salgado H C
Published: August 2012

We investigated the acute and chronic effects of converting enzyme inhibitors (captopril or enalapril) and of angiotensin II receptor blockade (DuP 753) on rapid (30-minute) baroreceptor resetting elicited by a prompt and sustained hypertensive response provoked by aortic constriction. Pressure-nerve activity curves, pressure at 50% of maximal baroreceptor activity, baroreceptor gain (slope of the curve), and systolic threshold pressure for baroreceptor activation were determined as indexes of baroreceptor function. A slight fall in mean arterial pressure after acute treatment with the converting enzyme inhibitor or DuP 753 was accompanied by a partial leftward curve shift, which is associated with a partial threshold shift and increase in gain. A maintained hypertensive stimulus caused a partial rightward curve shift and partial (49% to 56%) threshold shift to hypertensive levels in both acutely treated and control rats. The hypertensive stimulus provoked a partial rightward curve shift and complete (88% to 94%) threshold shift to hypertensive levels in chronically treated rats. The effect of enalapril on baroreceptor function was unaltered by the bradykinin antagonist Hoe 140. These data demonstrate that chronic inhibition of converting enzyme or blockade of angiotensin II receptors facilitates rapid resetting of the baroreceptors to hypertensive levels caused by partial aortic constriction without a change in baroreceptor sensitivity.
Physiopathogenesis of acute aortic coarctation hypertension in conscious rats.
Authors: Salgado H C , Skelton M M , Salgado M C , Cowley A W
Published: August 2012

We investigated the role of vasopressin, angiotensin II, and catecholamines in the onset of acute (45-minute) aortic coarctation hypertension in conscious rats. Partial aortic constriction was performed by means of a pneumatic cuff placed around the abdominal aorta above the renal arteries for 15 or 45 minutes. A sham-operated group was used as control. Mean carotid pressure before aortic constriction did not differ between rat groups. Aortic constriction produced a similar increase of mean carotid pressure during 15 minutes (36 +/- 3 to 37 +/- 3 mm Hg above basal levels) and 45 minutes (37 +/- 2 to 39 +/- 3 mm Hg). Plasma vasopressin concentration after 15 minutes of coarctation (4.4 +/- 0.5 pg/mL) did not differ from that observed in control rats (3.0 +/- 0.8 pg/mL), whereas after 45 minutes, it was significantly higher (14.3 +/- 3.3 pg/mL). Plasma renin activity increased significantly after coarctation (21.7 +/- 4.1 and 29.9 +/- 2.9 ng angiotensin I/mL per hour, at 15 and 45 minutes, respectively) when compared with control rats (3.9 +/- 0.5 ng angiotensin I/mL per hour). After coarctation, plasma norepinephrine concentration was consistently reduced, whereas plasma epinephrine concentration did not differ from control rats. In conclusion, these data provide evidence for an effective vasopressor role for vasopressin in the genesis of acute (45-minute) aortic coarctation hypertension in conscious rats. In addition, although the results confirm that the renin-angiotensin system participates earlier in the onset of coarctation hypertension, they rule out a significant vasopressor role for catecholamines in the early development of hypertension.
Localization of the anterior hypothalamic angiotensin II pressor system.
Authors: Hartle D K , Lind R W , Johnson A K , Brody M J
Published: August 2012

Previous studies by this laboratory have shown that an electrolytic lesion of tissue surrounding the anteroventral third cerebral ventricle (AV3V) produces pressor deficits to both intravenously (i.v.) and intracerebroventricularly (i.c.v.) administered angiotensin II (AII). These studies were designed to identify the neural substrates critical to the central AII pressor response. The AII pressor system was mapped employing a spectrum of overlapping electrolytic lesions within the medial preoptic-anterior hypothalamic area. The effect of each lesion on the pressor response to AII (i.c.v.) was tested in each animal, which was then grouped as a responder (R) or nonresponder (NR). The extent of damage produced by lesions that abolished the AII response was mapped. Bilateral destruction of tissue along the lamina terminalis (LT) either below or at the level of the anterior commissure eliminated the AII pressor response as did destruction of tissue near the margin of the preoptic and anterior hypothalamic nuclei. These data suggested that an AII pressor pathway originating in the ventral AV3V region ascends along the LT to the level of the anterior commissure and then descends through the anterior hypothalamus. The path of the descending projection through the anterior hypothalamus was ascertained by making a series of horizontal knife cuts. Transections were found that effectively eliminated the central AII pressor response without impinging upon the LT. It is concluded that the anterior hypothalamus contains an efferent pathway from the AV3V region associated with the central AII pressor response.
The sympathetic system in hypertension. State-of-the-art review.
Authors: Abboud F M
Published: August 2012

One may postulate a genetic defect in membrane permeability, in the transport of sodium, or in the sodium pump in vascular muscle which could account for increased intracellular sodium and enhanced vascular contractility. If the electrogenic sodium pump is overactive, as in SHR, its inhibition may lead to significant depolarization and greater contraction. Sympathetic innervation may be essential for the development of membrane abnormality as well as for the development of hypertrophic vascular changes, both of which augment contraction and vascular tone. A similar membrane defect at the sensory endings of arterial stretch receptors may account for impaired arterial baroreceptor reflexes seen in very early phases of hypertension or, in some genetic models, before hypertension develops. This defect may be related to the sodium pump or sodium transport in the receptor region and cause a decrease in baroreceptor discharge and in the strain-sensitivity of the baroreceptors, resulting in exaggerated sympathetic drive. Further information is needed on the baroreflex control of various efferents in hypertension. Another membrane defect at the adrenergic nerve terminals may facilitate release of endogenous NE. Excessive salt intake may unmask or exaggerate the membrane defects. In the central nervous system a defect in glutamine, NE, or GABA receptors may contribute to a high central sympathetic drive. Greater receptor affinity to various pressor neuropeptides such as angiotensin and leucine enkephalin or greater release of these peptides may also account for the excessive CNS sympathetic activation or impairment of baroreflexes at a central level. Cardiac receptors may have a variable influence on sympathetic drive in the various stages of hypertension, depending on the degree of cardiac hypertrophy or cardiac size. Finally, increased renal afferent nerve activity may provoke an increase in sympathetic activity and provide a link between natriuretic factors and the sympathetic nervous system in hypertension.
H-77: a potent new renin inhibitor. In vitro and in vivo studies.
Authors: Szelke M , Leckie B J , Tree M , Brown A , Grant J , Hallett A , Hughes M , Jones D M , Lever A F
Published: August 2012

Chemical modification of the backbone at the cleavage site in the (6-13)-octapeptide of equine angiotensinogen resulted in greatly increased binding affinity and resistance to cleavage by renin. The D-His6-Tyr13 octapeptide analog containing the reduced bond -CH2-NH-instead of a peptide bond -CO-NH- at the Leu10-Leu11 linkage (H-77) was a powerful in vitro inhibitor of canine renin (IC50 = 24nM). It gave an IC50 of 1 microM against human renin and 0.6 microM against rat renin. In sodium-depleted conscious dogs, infusion of H-77 caused dose-related falls of plasma angiotensin I plasma angiotensin II concentration and mean arterial pressure; the minimum effective dose was 0.1 mg . kg-1 hr-1. Similar infusions of H-77 in chronically catheterized rats have no effect on blood pressure or plasma angiotensin II concentration. Thus, the in vitro effect of H-77 as an inhibitor of renin in dog, human, and rat plasma was paralleled by its action in the whole animal.
In vivo and in vitro alterations of active and inactive plasma renins in the rat.
Authors: Barrett J D , Eggena P , Sambhi M P
Published: August 2012

The levels of active, inactive, and total renin (trypsin treatment) were measured in rat plasma before and after in vivo stimulation or suppression of active plasma renin. Stimulation of active renin was accompanied by either an increase (low sodium diet), no change (pentobarbital anesthesia plus hemorrhage), or fall (pentobarbital anesthesia) in the plasma levels of inactive renin, while suppression of active renin was accompanied by a fall (high sodium diet) or mild but nonsignificant increases (clonidine or saline infusion) of the inactive enzyme. These results suggest the possible independence of in vivo regulation of active and inactive renin in the rat. Trypsin activation of plasma fractions obtained by isoeletric focusing indicated a minimum of three activable forms of inactive renin (pH 4.4, 4.6, 4.8). Inactive enzymes could not be completely separated from active renins by this technique. Isoelectric focusing indicated a similar lowering of the isoelectric points of the five detectable active renins of rat plasma following in vivo stimulation of the renin system (ether anesthesia plus hemorrhage) or trypsin treatment of normal rat plasma before fractionation. These results indicate that similar renins are activated both in vivo and in vitro. Although trypsin is not the physiological activator of renin, a similar enzymatic cleavage resulting in activation appears to occur in vivo.
Biochemical similarity of partially purified inactive renins from human plasma and kidney.
Authors: Atlas S A , Sealey J E , Hesson T E , Kaplan A P , Ménard J , Corvol P , Laragh J H
Published: August 2012

Inactive renin was partially purified from 4.5 liters of human plasma (502-fold, specific activity 0.8 X 10(-3) Goldblatt units/mg protein) and from 207 g renal cortex (103-fold, 52 X 10(-3) Goldblatt units/mg). In contrast to active renin, inactive renin from each source bound to Cibacron blue-agarose and was unable to bind to pepstatin-Sepharose. Both plasma and renal inactive renin had weaker affinity for anion-exchange resins than the active form, both bound to concanavalin A-Sepharose and were eluted with carbohydrate, and both bound tightly to hydrophobic gels. Each substance could be isolated in a completely inactive form during small-scale pilot studies, but "spontaneous" activation did occur, to a limited degree, during large-scale purification; this was possibly due to a plasma serine protease that fractionated with inactive renin during the initial purification steps. Both plasma and renal inactive renin were activated irreversibly by trypsin. Following activation, each substance lost it ability to bind to Cibacron blue-agarose. Each could be activated fully by acidification at 4 degrees C, but this activation was reversed during subsequent incubation at higher temperature and pH. There was no evidence of acid protease activity in either preparation. Activated inactive renin from both plasma and kidney were identical to partially-purified active renal renin in terms of pH optimum (pH 5.5-6.0) and reaction kinetics (Km 0.8-1.3 microM) with homologous angiotensinogen, noncompetitive inhibition by pepstatin (ki 2.5-3.5 microM), and an identical inhibition profile by monospecific antirenin antibodies. These results suggest that inactive renin from plasma and kidney may be the same substance and that their activated forms are similar to the endogenously produced active enzyme, consistent with the possibility that inactive renin is a precursor of circulating active renin.
Central and peripheral indices of sympathetic activity after blood pressure lowering with enalapril (MK-421) or hydralazine in normotensive rats.
Authors: Kohlmann O , Bresnahan M , Gavras H
Published: August 2012

Various antihypertensive drugs have different effects on vasoactive mechanisms. In normotensive Wistar rats, we investigated the effects on plasma and tissue catecholamines of chronic treatment with two agents: MK-421, an angiotensin converting-enzyme inhibitor (CEI), and hydralazine, a vascular smooth muscle relaxant. Both agents lowered blood pressure via arteriolar dilation, to the same final level. However, hydralazine stimulated the renin-angiotensin system and elevated the plasma norepinephrine (NE) and epinephrine (E) levels, whereas MK-421 did not. In MK-421-treated animals, NE, E, and the ratio of E/NE were decreased in the brain stem, and this ratio was increased in the heart. In hydralazine-treated rats, the catecholamine levels were unchanged in the brain stem and heart. The turnover rate of NE was significantly reduced in the brain stem and heart of MK-421-treated rats, whereas, after hydralazine, the turnover rate in the heart was increased (decreasing the half-life of NE by about 50%), indicating increased sympathetic activity. Thus, elimination of angiotensin II (AII) by CEI is associated with decreased sympathetic activity in both the brain stem and heart, whereas an equipotent antihypertensive action by smooth muscle relaxation leads to stimulation of both the renin-angiotensin and the sympathetic systems. These differences are more readily apparent by measurement of catecholamine turnover rates in tissues than of catecholamine levels, and they may account for the different hemodynamic effects of the two agents, even though both drugs act through arteriolar dilation.
A new form of inactive renin in rat brain. A latent renin.
Authors: Inagaki T , Inagami T
Published: August 2012

A new inactive (latent) form of renin was found in rat brain extract. It is activated by sulfhydryl compounds such as dithiothreitol but not by proteases such as trypsin. The activated form of latent renin in crude brain extract was again inactivated by the disulfide compound sodium tetrathionate. Latent renin was separated, at least partially, from active renin by affinity chromatography on Affi-Gel Blue. In contrast to a marked (10-fold) increase of latent renin by dithiothreitol, the enzyme activity of active renin was increased by less than 50% by this sulfhydryl compound. Thus, the major part of the activating effect of dithiothreitol does not seem to be due to its effect on renin substrate. Latent renin showed affinity for pepstatin-Sepharose gel. These properties indicate that latent renin is different from inactive renin of the zymogen type, which is activated by protease or acid treatment but not by sulfhydryl compounds and does not show affinity to pepstatin. Latent renin has a molecular weight of 45,000 and is reduced to 34,000 upon activation by dithiothreitol. This observation suggests that latent renin may be a renin-inhibitor complex.
Defective synthesis of vasodilator prostaglandins in the spontaneously hypertensive rat.
Authors: Martineau A , Robillard M , Falardeau P
Published: August 2012

Results of in vitro studies performed in different laboratories have led to the hypothesis that in spontaneously hypertensive rats (SHR), the biosynthesis of the vasodilator prostaglandins (PG) I2 and E2 increases secondarily to the rise in the arterial pressure, as a protective mechanism for reducing the severity of hypertension. In this study, this hypothesis was tested in vivo in SHR and control Wistar-Kyoto (WKY) rats under normal and high sodium diets. The 24-hour urinary excretion of 2,3-dinor-6-oxo-PGF1 alpha, an endogenous metabolite of PGI2, was used as an index of the total production of PGI2 in the rats, whereas the urinary levels of PGE2 were used as an index of the renal production of this prostaglandin. Urinary levels of PGE2, obtained at 10 and 12 weeks of age, were always lower in SHR than in WKY rats and were not influenced by dietary sodium. In WKY and SHR on normal diets, the urinary levels of 2,3-dinor-6-oxo-PGF1 alpha did not differ significantly. However, the chronic administration of a high sodium diet (5.9% NaCl) was accompanied by a significant and sustained rise in the urinary excretion of 2,3-dinor-6-oxo-PGF1 alpha in the order of 30% to 50% in WKY but not in SHR, a finding similar to that in Dahl rats. These results point to the existence of an impaired capacity in SHR to synthesize vasodilator prostaglandins in vivo, contrary to the situation prevailing in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)
Potassium protection against lesions of the renal tubules, arteries, and glomeruli and nephron loss in salt-loaded hypertensive Dahl S rats.
Authors: Tobian L , MacNeill D , Johnson M A , Ganguli M C , Iwai J
Published: August 2012

Dahl S rats (20/group) were given three Purina diets for 24 weeks: 4% NaCl-no added potassium (BP 171 mm Hg); 4% NaCl-3.8% K citrate (BP 174 mm Hg); 4% NaCl-2.6% KCl (BP 173 mm Hg). The added potassium did not lower blood pressure (BP) but strikingly reduced microscopic renal lesions. Focal tubular dilation was scored blindly (100, severest lesions; 0, normal). Scores were: renal cortex: no potassium (41); K citrate (20); KCl (22), 50% improvement p less than 0.001; outer medulla: no potassium (79); K citrate (54); KCl (58), 30% improvement p less than 0.001; renal papilla: no potassium (49); K citrate (28); KCl (28), 43% improvement, p less than 0.001. Both K citrate and KCl also eliminated the thickened walls and relatively narrowed lumens of the hypertensive renal arterioles, without lowering BP. In these same rats, the wall thickness of arterioles from 20 normotensive salt-resistant (R) rats on 4% NaCl averaged 18.9 mu vs 26.1 mu in arterioles from 18 hypertensive salt-sensitive (S) rats on 4% NaCl with no added potassium. Adding either KCl or K citrate to the 4% NaCl diet strikingly reduced the wall thickness to that found in the R rat, even though the BP was not reduced at all. Potassium did not lower the high BP but apparently reduced the severity of the arteriolar lesions resulting from that high BP.(ABSTRACT TRUNCATED AT 250 WORDS)
Cerebrospinal fluid kinins and cardiovascular function. Effects of cerebroventricular melittin.
Authors: Thomas G R , Thibodeaux H , Margolius H S , Privitera P J
Published: August 2012

Biochemical and histochemical studies have identified components of the kallikrein-kinin system in the brain. The present study was designed to determine whether kinins could be detected in cerebrospinal fluid (CSF) and if these levels could be altered. Endogenous CSF samples were taken from the cisterna magna of pentobarbital-anesthetized mongrel dogs (n = 11) and were shown to contain 13 +/- 3 pg/ml (mean +/- SE) of immunoreactive kinin ( ikinin ) measured by RIA. The ( ikinin ) samples showed complete parallelism to standard synthetic bradykinin. Ventriculocisternal perfusion of the anesthetized dog brain with artificial CSF alone at a rate of 0.191 ml/min for 240 minutes had little or no effect on basal levels of CSF ( ikinin ), mean arterial pressure (MAP), or heart rate (HR). Melittin (20 microM), an activator of membrane-bound kallikrein, added to the perfusion system for 60 minutes caused a significant and sustained elevation in CSF ( ikinin ) levels from 19 pg/ml up to a maximum of 194 pg/ml (p less than 0.01). This change was accompanied by a prolonged increase in MAP of up to 22 mm Hg (p less than 0.01) and a transient increase in HR of 14 bpm (p less than 0.05). Melittin (2 microM) had no significant effect on CSF ( ikinin ) levels or MAP, but resulted in a sustained increase in HR of 17 to 25 bpm (p less than 0.01). The cardiovascular responses to centrally administered melittin (20 microM) were attenuated by concomitant administration of aprotinin (2000 KIU/ml). This study establishes the existence of ( ikinin ) in the CSF, shows that such levels can be manipulated, and suggests that central kinins may be involved in the modulation of cardiovascular function.
Regional sources of free and sulfoconjugated catecholamines in hypertension.
Authors: Kuchel O , Buu N T , Roy P , Hamet P , Larochelle P , Genest J
Published: August 2012

To elucidate the sources of free catecholamines (CA) and their sulfates in hyperadrenergic essential hypertensives (EH), their arteriovenous differences were determined radioenzymatically and by sulfatase hydrolysis (with correction for cross-contamination) across several organs and regions in 16 hyperadrenergic essential hypertensive patients. Comparison with arterial concentrations showed that: the adrenal venous outflow contains 240 times more free epinephrine (E), 55 times more free norepinephrine (NE), and 7 times more free dopamine (DA) concentrations, but E, NE, and DA sulfates are not different; free E concentrations are lower in the peripheral venous blood; NE sulfate concentrations are higher in the superior vena cava (p less than 0.05 for all differences noted). The data suggest the following conclusions for hyperadrenergic EH patients: with the exception of NE sulfate added into the superior vena cava region, no other organ or region can be associated with a net DA or NE sulfate release. The proportional adrenal vein concentrations of DA:NE:E are approximately 1:10:50, which are very close to those seen in other studies performed under different degrees of stress. Free E is extracted in peripheral tissues. The DA surges in hyperadrenergic EH patients probably result from the pulsatile, predominantly adrenal, release of free DA.
Blood pressure lowering diminishes age-related changes in the rat aortic intima.
Authors: Haudenschild C C , Chobanian A V
Published: August 2012

These studies were undertaken to determine whether age-related changes in the aortic intima can be inhibited by prolonged blood pressure lowering. Normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were treated with a combination of chlorothiazide, reserpine, and hydralazine beginning at 20 weeks of age and continuing until 62 weeks. Aortic morphology was assessed at the termination of the study by light and electron microscopy. Average systolic blood pressures during the final 6 months of therapy were: for untreated WKY, 147 +/- 5 mm Hg (mean +/- SE); for treated WKY, 110 +/- 2; for untreated SHR, 206 +/- 3; and for treated SHR, 104 +/- 4. Intimal and medial abnormalities were maximal in untreated SHR, while untreated WKY showed moderate changes consistent with their age. In contrast, both treatment groups exhibited relatively minimal alterations despite their advanced age. The occurrence of intimal lesions in individual animals correlated with the average level of blood pressure during therapy. These data suggest that blood pressure reduction, even in normotensive animals, may reduce the effects of aging on the arterial wall.