摘要:

In 1980, a randomized trial was conducted among 476 Dutch newborn infants to study the effect of a low or normal sodium diet on blood pressure during the first 6 months of life. At the end of the trial, systolic blood pressure in the low sodium group (n = 231) was 2.1 mm Hg lower than in the control group (n = 245). To investigate whether contrasting levels of sodium intake in infancy are associated with blood pressure differences in adolescence, we measured blood pressure in 167 children from the original cohort (35%) after 15 years of follow-up. We assessed the differences in systolic and diastolic blood pressure levels between the diet groups using a multivariate regression model with adjustment for potential confounders. The adjusted systolic blood pressure at follow-up was 3.6 mm Hg lower (95% confidence interval, -6.6 to -0.5) and the diastolic pressure was 2.2 mm Hg lower (95% confidence interval, -4.5 to 0.2) in children who had been assigned to the low sodium group (n = 71) compared with the control group (n = 96). These findings suggest that sodium intake in infancy may be important in relation to blood pressure later in life. (Hypertension. 1996;29:913-917.)

ISSN:0194-911X    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Salt sensitivity is a heritable trait that is a hallmark of hypertension in black Americans. Genes encoding adrenergic receptors are candidate loci for the inheritance of this hypertension-related trait because of the role of these receptors in the regulation of renal sodium excretion and vascular tone. We performed this study to determine whether these loci are responsible for some of the phenotypic variation in salt sensitivity. Hypertensive black American probands were ascertained, followed by sequential ascertainment of adult sib pairs among the first-, second- and third-degree relatives of the proband. Both hypertensive and normotensive siblings were tested for salt sensitivity by an intravenous sodium-loading, lasix volume-depletion protocol. Genotyping was performed with restriction fragment length polymorphisms in genomic DNA probed with clones containing the beta2-and alpha2c10-adrenergic receptor genes. A total of 109 sib pairs was evaluated. Salt sensitivity was defined as the change in blood pressure in each individual, comparing the sodium-loaded with the volume-depleted state. Systolic pressure decreased by an average of 9.0 +/- 9%, diastolic pressure by 1.5 +/- 11%, and mean arterial pressure by 5.0 +/- 9%. Neither blood pressure nor salt sensitivity was linked at the alpha2c10-adrenergic receptor locus. No evidence suggested that systolic salt sensitivity and baseline blood pressure were linked at the beta2-adrenergic receptor locus. Model-independent sib pair linkage analysis suggested that diastolic blood pressure response to sodium loading/volume depletion is linked at the beta (2) -adrenergic receptor locus (P < .006). Evidence for linkage was significant at the .05 level after adjustment for the number of phenotypic traits examined. (Hypertension. 1997;29:918-922.)

ISSN:0194-911X    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

This study aimed to characterize the influence of dietary salt intake on the gene expression of angiotensin II type 1 (AT1) receptor subtypes in different organs. Male Sprague-Dawley rats were fed low salt (0.2 mg/g), normal salt (6 mg/g), or high salt (40 mg/g) diets for 5, 10, and 20 days. mRNA levels for the two AT1receptor subtypes were determined in adrenal gland, kidney, liver, and lung. In all of the organs examined, with the exception of the adrenal glands, low salt diet led to a transient decrease in the abundance of AT1Areceptor mRNA but not of AT1BmRNA, which reached their nadirs between days 5 and 10 of feeding. In the adrenal gland, in which the AT1Breceptor is predominant, low salt diet led to a transient increase in the expression of this receptor gene, with a maximum around day 10 of feeding. High salt diet exerted no significant influence on AT1receptor gene expression in these organs. These findings indicate that the rate of salt intake, in particular, a reduction of salt intake, significantly influences AT1receptor gene expression in an organ-, time-, and subtype-dependent fashion. It appears that AT1receptor subtypes are differentially influenced by low salt intake, in that AT1Breceptor gene expression increases and AT1Areceptor gene expression decreases in this situation. This differential response of AT1receptor gene expression may be relevant for the organism to be able to adapt to a reduction in oral salt intake. (Hypertension. 1997;29:923-929.)

ISSN:0194-911X    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Delineating the role that diet plays in blood pressure levels in children is important for guiding dietary recommendations for the prevention of hypertension. The purpose of this study was to investigate relationships between dietary nutrients and blood pressure in children. Data were analyzed from 662 participants in the Dietary Intervention Study in Children who had elevated low-density lipoprotein cholesterol and were aged 8 to 11 years at baseline. Three 24-hour dietary recalls, systolic pressure, diastolic pressure, height, and weight were obtained at baseline, 1 year, and 3 years. Nutrients analyzed were the micronutrients calcium, magnesium, and potassium; the macronutrients protein, carbohydrates, total fat, saturated fat, polyunsaturated fat, and monounsaturated fat; dietary cholesterol; and total dietary fiber. Baseline and 3-year longitudinal relationships were examined through multivariate models on diastolic and systolic pressures separately, controlling for height, weight, sex, and total caloric intake. The following associations were found in longitudinal analyses: analyzing each nutrient separately, for systolic pressure, inverse associations with calcium (P < .05); magnesium, potassium, and protein (all P < .01); and fiber (P < .05), and direct associations with total fat and monounsaturated fat (both P < .05); for diastolic pressure, inverse associations with calcium (P < .01); magnesium and potassium (both P <.05); protein (P < .01); and carbohydrates and fiber (both P < .05), and direct associations with polyunsaturated fat (P < .01) and monounsaturated fat (P < .05). Analyzing all nutrients simultaneously, for systolic pressure, direct association with total fat (P < .01); for diastolic pressure, inverse associations with calcium (P < .01) and fiber (P < .05), and direct association with total and monounsaturated fats (both P < .05). Results from this sample of children with elevated low-density lipoprotein cholesterol indicate that dietary calcium, fiber, and fat may be important determinants of blood pressure level in children. (Hypertension. 1997;29:930-936.)

ISSN:0194-911X    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

2 SD of mean of control group) (group 1) with normotensive elite veteran athletes who had comparable cardiac hypertrophy (group 2) and sedentary normotensive subjects as controls (group 3). The groups (n = 14 each) were matched for age (+/- 2 years) and sex. We analyzed echocardiographic digitized data quantitatively by means of a calibrated 256 gray level digitization system to calculate midseptal and midposterior end-diastolic and end-systolic mean gray levels and to derive the so-called cyclic variation index, ie, the percent mean gray level variation during the cardiac cycle. Echocardiographic parietal and septal thicknesses and masses were evaluated according to the Penn convention. Left ventricular mass index (adjusted for height) overlapped between groups 1 and 2 (187.1 +/- 17.5 and 181.3 +/- 19.3 g/m, respectively; P = NS), whereas it was obviously smaller in control subjects (93.1 +/- 18.6 g/m; P < .001 for both). According to inclusion criteria, both septal and posterior wall thicknesses were comparable in athletes and hypertensive subjects, and they were higher than in the control group (P < .0001). The hypertensive subjects showed a significantly lower cyclic variation index than the control and athlete groups for both the septum (P < .001) and posterior wall (P < .001); no statistical difference was found between athletes and control subjects for this parameter. In conclusion, abnormalities of two-dimensional echocardiographic gray-level distribution are present in hypertensive hypertrophied individuals but seem unrelated to the degree of echocardiographic hypertrophy as such. An altered collagen network distribution or a decrease in capillary distribution in severe myocardial hypertrophy, secondary to pressure-volume overload in hypertension with other yet unknown mechanisms, could help to explain our findings. Further work is needed to establish the prognostic, clinical, and therapeutic implications of these findings. (Hypertension. 1997;29:937-944.)

ISSN:0194-911X    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Calcitonin gene-related peptide (CGRP) is a potent vasodilator neuropeptide. We previously demonstrated that neuronal CGRP expression is significantly increased in deoxycorticosterone (DOC)-salt hypertensive rats. To determine the hemodynamic role of CGRP in this setting, we used CGRP8-37, a specific CGRP receptor antagonist. DOC-salt hypertension was induced in Sprague-Dawley rats. To control for DOC pellet implantation, left nephrectomy, and/or saline drinking water, we also studied four normotensive groups. Four weeks after the initiation of each protocol, all rats had intravenous (for drug administration) and arterial (for continuous mean arterial pressure monitoring) catheters surgically placed and were studied in the conscious, unrestrained state. Baseline mean arterial pressure was higher in the DOC-salt than normotensive rats (175 +/- 5 versus 119 +/- 4 mm Hg, P < .001). Vehicle administration did not alter mean arterial pressure in any group, and CGRP (8-37) administration (bolus doses of 3.2 x 104or 6.4 x 104pmol/L) did not change mean arterial pressure in the four normotensive groups. However, CGRP8-37administration to the DOC-salt rats rapidly and significantly increased mean arterial pressure at both the lower dose (9 +/- 1 mm Hg, P < .001) and higher dose (14 +/- 1 mm Hg, P < .001). In addition, the increase in mean arterial pressure between the two CGRP8-37doses was also significant (P < .01), indicating a dose-dependent response. We conclude that the increase in neuronal CGRP expression in DOC-salt hypertension plays a compensatory vasodilator role to attenuate the elevated blood pressure. These results provide the first conclusive evidence that CGRP plays a direct role in DOC-salt hypertension. (Hypertension. 1997;29:945-950.)

ISSN:0194-911X    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

FR 173657, the first effective nonpeptide kinin B2receptor antagonist, has been tested in four preparations from different species (human, pig, rabbit, and guinea pig). The new compound shows high apparent affinity for the four B2receptors, with pA2values ranging from 8.2 to 9.4. FR 173657 is a selective B2receptor antagonist that does not interact with human, pig, or rabbit B1receptors. The new compound is extremely specific for the kinin B2receptors as it does not affect the myotropic effects of norepinephrine, endothelin-1, or 5-hydroxytryptamine in the human umbilical vein; the contractions elicited by substance P and angiotensin II in the rabbit jugular vein or those produced by acetylcholine and histamine in the guinea pig ileum; or the relaxation of the pig coronary artery induced by norepinephrine and substance P. FR 173657 acts as a competitive antagonist over an extended range of concentrations on human and rabbit B2receptors, whereas on pig and guinea pig receptors, it depresses the maximal effect of bradykinin and thus appears to act as a noncompetitive antagonist. (Hypertension. 1997;29:951-956.)

ISSN:0194-911X    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

We have recently characterized a novel angiotensin II/vasopressin (Ang II/AVP) dual receptor coupled to adenylate cyclase and responding with equal sensitivity to Ang II and AVP. To gain insight into putative renal physiological roles of the dual Ang II/AVP receptor, we determined its pharmacological binding properties and renal immunocytochemical distribution. The effective displacement of [(3) H]AVP by [1-deamino-Val14, D-Arg8]-vasopressin (DVDAVP), a specific antidiuretic AVP analogue, supports a V2-type AVP receptor characteristic of the Ang II/AVP receptor. Displacement of125I-Ang II by losartan but not by PD 123319 defines the Ang II/AVP receptor as a novel AT1receptor isoform coupled to adenylate cyclase, in contrast to prototype Ca2+-mobilizing AT1receptors. Neither Ang II nor AVP displace each other, corroborating the predicted discrete binding domains for Ang II and AVP but presenting an enigma for the dissection of putative Ang II-and AVP-specific hierarchical roles of the dual Ang II/AVP receptor. The renal cytolocalization of the Ang II/AVP receptor to the outer medullary thick ascending limb tubules and inner medullary collecting ducts is consistent with the well-established AVP stimulation of sodium and water reabsorption in these tubules. These data suggest that the Ang II/AVP receptor might provide the molecular basis for the observed similar stimulatory effects of Ang II and AVP on renal tubular sodium and fluid reabsorption at physiological hormone concentrations. (Hypertension. 1997;29:957-961.)

ISSN:0194-911X    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Two dopamine D1-like receptors have been cloned from mammals, the D1and D5receptors, also known as D1Aand D (1B) receptors, respectively, in rodents. Although D1-like receptors are known to stimulate renin release, the receptor subtype mediating this action has not been determined. We investigated D1receptor subtype expression in rat juxtaglomerular cells obtained after enzymatic dispersion of kidney cortex and differential centrifugation. Juxtaglomerular cells in primary culture were immunocytochemically 85% to 95% renin positive. These cells expressed the D1Abut not the D1Breceptor (mRNA and protein). D1-like receptor function was demonstrated by a concentration-dependent stimulation of cAMP production by dopamine (n = 5-9 per group). Fenoldopam, a D1-like receptor agonist, also caused a concentration-dependent increase in cAMP production and renin secretion that was blocked by the selective D1-like receptor antagonist SCH23390 (n = 4-13 per group). Although the D1ligands do not distinguish between the cloned D1-like receptors, the actions of fenoldopam were due to occupancy of the D1Areceptor: (1) the D1Breceptor, the only other mammalian D1-like receptor, is not expressed in juxtaglomerular cells; (2) antisense but not sense D1Aoligonucleotides completely blocked the stimulatory effect of fenoldopam on cAMP production and renin secretion. We conclude that there is selective dopamine receptor gene expression in juxtaglomerular cells; the dopamine receptor subtype linked to the stimulation of cAMP and renin secretion in juxtaglomerular cells is the D1Asubtype. (Hypertension. 1997;29:962-968.)

ISSN:0194-911X    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

We evaluated whether a minor impairment of the L-arginine-nitric oxide pathway would affect the desensitization of vascular alpha-adrenoreceptor and pressure diuresis induced by prolonged intravenous infusion of phenylephrine (an alpha-adrenoreceptor agonist) in conscious Wistar-Kyoto rats. We examined dose-pressor-response curves to phenylephrine after an intravenous infusion of phenylephrine (2.5 micro gram [center dot] kg-1*symbol min-1) or saline for 9 hours with and without concomitant infusion of Nomega-L-arginine methyl ester (L-NAME) given to partially inhibit the L-arginine-nitric oxide pathway. In addition, to evaluate the effect of plasma volume loss on the pressor response to phenylephrine, we evaluated the dose-pressor-response curves to phenylephrine after intravenous injection of furosemide (5 mg/kg) or infusion of phenylephrine (5 micro gram [center dot] kg-1[center dot] min (-1)) for 9 hours. The renin-angiotensin, vasopressin and autonomic nervous systems were blocked before the examination of dose-pressor responses. Prolonged infusion of phenylephrine (2.5 micro gram [center dot] kg (-1) [center dot] min-1) shifted the dose pressor-response curve to this agent rightward, with significantly increased log ED50(the dose needed to reach 50% of the maximal response) to a similar extent in both L-NAME-treated (0.51 +/- 0.05 versus 0.93 +/- 0.07 micro gram/kg) and -untreated (0.79 +/- 0.06 versus 1.08 +/- 0.03 micro gram/kg) rats. The log ED50value after phenylephrine infusion (5 micro gram [center dot] kg (-1) [center dot] min-1) was significantly higher than that after furosemide injection (1.28 +/- 0.06 versus 1.02 +/- 0.01 micro gram/kg, respectively, P < .01), although the two treatments induced a similar loss of plasma volume. The slope in the linear relationship between the average change in mean arterial pressure during the 9-hour infusion period and the rate of urine excretion was significantly depressed in L-NAME-treated versus control rats (L-NAME: 0.057 mL [center dot] kg-1[center dot] h-1[center dot] mm Hg-1, control: 0.146 mL [center dot] kg-1[center dot] h-1[center dot] mm Hg-1, P < .05). In conclusion, a minor impairment of the L-arginine-nitric oxide pathway does not appear to interfere with the desensitization of vascular alpha-adrenoreceptor but does inhibit the pressure-diuresis response in conscious normotensive rats. (Hypertension. 1997;29:969-975.)

ISSN:0194-911X    

出版商:OVID    

年代:1997

数据来源: OVID