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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study was to determine if the reflex response to a saline load is altered in the obese Zucker rat. The obese Zucker rat is a genetic model of obesity and insulin-resistant diabetes that has been reported to have high blood pressure. We examined the reflux renal responses to volume expansion in both anesthetized obese and lean Zucker rats. Initial blood pressure was significantly elevated in the obese Zucker rats compared with the lean controls. Urine flow and sodium excretion from innervated and denervated kidneys were measured before and after volume expansion with normal saline. Volume expansion resulted in significantly less urine flow and sodium excretion in the obese than the lean Zucker rats. This response was evident in both the intact and denervated kidneys. Rats were then infused with atrial natriuretic peptide (ANP) to determine if natriuretic and diuretic responses were altered in these rats. The diuretic action of ANP was not significantly reduced in the obese Zucker rat. However, the natriuretic action of ANP was significantly attenuated in the obese rats. These results indicate that the reflux response to an acute saline load is attenuated in the obese Zucker rat and that this decreased response may be due to a reduction in the direct action of ANP on the kidney.
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PMID:Reduced renal responses to an acute saline load in obese Zucker rats. 183 69

Atrial natriuretic peptide is stored by atrial myocytes in secretory granules, known as atrial specific granules, and is released from these granules by exocytosis. We have isolated a group of atrial proteins by affinity chromatography that bind to atrial specific granules in a calcium-dependent manner. The two major proteins isolated (32.5 kd and 67 kd) are calcium-binding proteins and have been identified as annexins V and VI by immunoblotting with specific antisera. The calcium dependence of their binding to atrial specific granules has been characterized in vitro and indicates that this interaction takes place at micromolar levels of calcium. In addition, the group of proteins isolated includes another calcium-binding protein of 20 kd, as well as GTP-binding proteins of 22 to 26 kd. Membrane interactions during exocytosis are presumably mediated by the interaction of specific proteins with the granule membrane. The properties of the proteins described here, and their ability to bind to atrial specific granules in a calcium-dependent manner, make them likely candidates in the search for regulatory proteins mediating atrial natriuretic peptide secretion.
Hypertension 1991 Nov
PMID:Annexins V and VI: major calcium-dependent atrial secretory granule-binding proteins. 183 52

In the first part of the text the main elements of renal physiology are mentioned as well as the role played by sodium-modulating hormones in the preservation of sodium and water homeostasis. A personal contribution concerns the release as well as the circadian rhythm of atrial natriuretic peptide (ANP) and of the digitalis-like substance (DLS). In the second part, the problem is dealt with from a pathophysiologic point of view, with reference made to the literature, and to our own data. In particular, the problem of essential hypertension with reduced levels of plasma renin activity (PRA) is thoroughly analyzed. As is well known, this kind of hypertension is characterized by normal plasma aldosterone levels associated with reduced kallikrein urinary excretion. The data we gathered not only confirmed these findings but also enabled us to point out other typical features of this particular kind of hypertension: normal values of vasopressin, elevation of ANP and DLS, hyperactivity of Na+/K+ cotransport. The introduction of a single variant in the sodium-modulating systems confirmed that the low PRA patient also behaves distinctively from a dynamic point of view. In fact, prostaglandin inhibition determines hypertension only in these patients, while both oral kallikrein administration and intravenous ANP administration were particularly effective because of a primitive deficit of the natriuretic paracrine systems paralleled by a compensatory increase of ANP. After identifying this group of hypertensive patients we intended to ascertain whether, even in the normal or high PRA patients, it was possible to identify a sub-group of subjects with altered sodium-modulation. The patients we examined were subdivided according to their hormonal and renal response to a saline load, and to angiotensin II, into "modulators" (with normal) and "nonmodulators" (with reduced sodium excretion capacity). An analysis of the hormonal characteristics of non-modulators identified an increased responsiveness of all sodium-modulation systems and not only of the renin-angiotensin-aldosterone system as pointed out by some other authors. The last part of the text is devoted to clinical and therapeutic problems. The behaviour of the daily blood pressure profile in patients with essential hypertension, and then the influence that sodium-modulating systems may have on pressure are discussed. The consequences of a progressive reduction in renal function on the circadian rhythm of arterial pressure are then assessed, and, at the same time, how renal impairment parallels the flattening of the daily pressure rate is observed.
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PMID:The kidney and essential hypertension. 183 73

Basal atrial natriuretic peptide levels and the response to exogenous atrial natriuretic peptide are influenced by dietary sodium intake. In view of interest in the therapeutic potential of elevating plasma atrial natriuretic peptide by inhibition of neutral endopeptidase 24.11, we studied the renal and hormonal effects of 200 mg of the oral endopeptidase 24.11 inhibitor candoxatril in eight patients with untreated essential hypertension on high sodium (350 mmol/day) and low sodium (10 mmol/day) diets. With endopeptidase 24.11 inhibition, plasma atrial natriuretic peptide increased more than twofold on low and high sodium diets (p less than 0.05). Plasma N-terminal pro-atrial natriuretic peptide increased on the high sodium intake but was unaffected by candoxatril. Urinary sodium excretion increased threefold on the low sodium and sixfold on the high sodium diet (p less than 0.05). The absolute increase in urinary sodium excretion during the 24 hours after treatment compared with placebo was 18 +/- 8 mmol on the low sodium and 98 +/- 34 mmol on the high sodium diet (p less than 0.05). Plasma renin activity was suppressed by treatment on the low but not on the high sodium diet (p less than 0.05). Blood pressure did not change in the 6 hours after a single dose of candoxatril. These findings show that sodium intake is a major determinant of the response to endopeptidase 24.11 inhibition. The lack of effect on N-terminal pro-atrial natriuretic peptide suggests that candoxatril does not influence cardiac secretion of atrial natriuretic peptide or catabolism of N-terminal pro-atrial natriuretic peptide, and the latter does not appear to play a role in the response to candoxatril.
Hypertension 1991 Dec
PMID:Dietary sodium and inhibition of neutral endopeptidase 24.11 in essential hypertension. 183 59

The relationships between atrial natriuretic peptide (ANP) and the renal sodium-modulating systems have not yet been completely examined. In particular, the relationships between ANP and the kinins system are almost unknown. We thus examined an extremely selected cohort of normotensive (n = 29, mean age 21 +/- 2 years) and hypertensive subjects (n = 51m mean age 21 +/- 2.9 years), both without hypertensive heredity. After 7 days under normal sodium intake (120 mEq of Na+/day), blood samples were taken in the morning on awaking, for radioimmunoassay of plasma levels of aldosterone, ANP and renin activity. Blood was again drawn after one active hour in orthostatism. We also evaluated urinary kallikrein excretion from urine collected over the previous 24 hours. Our results showed higher plasma levels of ANP in young hypertensives than in normotensives (statistical significance p less than 0.0025). Urinary excretion of kallikrein was markedly reduced (p less than 0.001) in the hypertensive group (0.46 +/- 0.3 U/24 h) compared to youths with normal blood pressure (0.79 +/- 0.24 U/24 h), in which a relationship between plasma ANP and urinary kallikrein was not evident; young hypertensives, on the other hand, showed an inverse correlation (r = -0.72; p less than 0.001). Finally, our investigation, aside from establishing the presence of high circulating ANP levels even at the initial phases of hypertension, points out a new possible means of feedback among sodium-modulating systems. The opposite relationship between ANP and urinary kallikrein excretion in young hypertensives could be attributed to reduced activity of the renal kinins system and a compensatory attempt on the part of ANP.
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PMID:[Correlations between circulation levels of natriuretic atrial peptide and urinary excretion of kallikrein in young normotensive and hypertensive subjects]. 183 37

Twenty-seven male and female black Zimbabweans hypertensive patients were matched by age and sex and compared to 27 normotensive subjects. All subjects were examined after dietary sodium depletion, followed by sodium loading. In addition to renin status and salt-sensitivity, urine aldosterone, renal prostaglandins, plasma atrial natriuretic peptide (ANP) and plasma endothelin were assessed. The following ethnic characteristics for Zimbabwean essential hypertensive patients were found: increased prevalence of salt-sensitive hypertension (66 pc); hyporesponsive renin-angiotensin system after contraction of circulating plasma volume; higher prevalence of low-renin hypertension (59 pc); suppressed renal prostaglandins, especially in low-renin hypertensives, suggesting suppression or deficit of renal kallikrein-kinin system; increased levels of ANP in low-renin hypertensive patients. Plasma endothelin was comparably increased in both normal- and low-renin hypertensive patients.
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PMID:Pathogenesis of systemic (essential) hypertension in Zimbabwean hypertensive patients. I. Humoral factors. 183 14

To clarify the possible role of elevated atrial natriuretic peptide (ANP) in the pathophysiology of preeclampsia, we measured ANP, renin activity (PRA), angiotensin II (Ang II), TXB2 (a stable metabolite of TXA2) and 6-keto-PGF1 alpha (a stable end product of PGI2) concentrations in the plasma of 19 normal pregnant women and 35 severe preeclamptic patients at term. Plasma ANP levels in the preeclamptic patients (n = 35, 71.5 +/- 3.8 pg/ml, mean +/- S.E.) and also umbilical plasma ANP (n = 35, 83.0 +/- 4.2 pg/ml) were significantly (p less than 0.01) higher than those of normal pregnant women plasma (n = 19, 58.7 +/- 3.7 pg/ml) and umbilical plasma (n = 19, 47.6 +/- 4.7 pg/ml). There was a significant (p less than 0.01) positive correlation between maternal ANP levels and fetal ANP levels (n = 54, r = 0.44). Plasma PRA and 6-keto-PGF1 alpha levels in preeclampsia were significantly (p less than 0.05) lower than those of normal pregnancy. The ratio of 6-keto-PGF1 alpha/TXB2 in preeclampsia was significantly (p less than 0.01) lower than that of normal pregnancy as we reported previously. There was no significant correlation between plasma ANP level and plasma PRA, Ang II, plasma TXB2 and 6-keto-PGF1 alpha concentrations. Moreover there was no significant correlation between plasma ANP level and the severity of preeclampsia. These data suggest the possibility of a transplacental crossing of ANP secreted by feto-placental unit, which might be, at least in part, responsible for the high ANP levels observed in preeclampsia. The ANP in preeclampsia is not related directly to hypertension, but it may play a substantial role in the regulation or normalization of blood volume and vascular reactivity.
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PMID:Maternal and fetal atrial natriuretic peptide levels, maternal plasma renin activity, angiotensin II, prostacyclin and thromboxane A2 levels in normal and preeclamptic pregnancies. 183 73

We have previously demonstrated the presence of binding sites for atrial natriuretic peptide (ANP) in human platelets. These sites have pharmacological characteristics similar to those of rat vascular smooth muscle. They are subject to regulation by circulating levels of ANP in plasma, varying inversely with the latter after high sodium intake, in arterial hypertension and congestive heart failure. We have now solubilized these platelet receptors with the nonionic detergent Triton X-100 (0.6%). The preparations were incubated with [125I]ANP in the presence of increasing concentrations of ANP-(99-126), ANP-(101-126), ANP-(103-126), and ANP-(103-123). The order of potency of these peptides to displace [125I]ANP was similar for the solubilized and particulate receptor. Bound [125I]ANP was covalently cross-linked to the receptor with 5 mM disuccinimidyl suberate. Autoradiography of the sodium dodecyl sulfate-polyacrylamide gel showed that [125I]ANP specifically interacts with a 125-kDa membrane component, some of which may be reduced by 2% mercaptoethanol or 10 mmol/L dithiothreitol to a 70-kDa species. A small proportion of a 70-kDa peptide is also found under nonreducing conditions. The concentration of ANP-(99-126) that inhibits binding of [125I]ANP by 50% to both the 125-kDa and the 70-kDa species was 0.1 nM, while that for ANP-(103-123) was 3 nM. The internally ring-deleted analog Des(Gln116,Ser117,Gly118,Leu119,Gly120)ANP -(102-121) or C-ANP displaced with equal potency ANP binding to the high and low mol wt (Mr) bands, as also found in cultured rat vascular smooth muscle cells, but not in the mesemteric arteries these cells are derived from. In the latter, C-ANP displaced only binding from the lower Mr band. These results show that the ANP receptor in human platelets is heterogeneous. There is one nonreducible species with of 125,000 Mr, another of similar Mr containing two disulfide-linked subunits of 70,000 Mr, and, to a lesser extent, a nonreducible 70-kDa species, in agreement with findings in other tissues in experimental animals.
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PMID:Solubilization and molecular characterization of the atrial natriuretic peptide (ANP) receptor in human platelets: comparison with ANP receptors in rat tissues. 184 77

An endogenous ouabain-like sodium pump inhibitor was demonstrated originally in serum or plasma of acutely extracellular fluid volume (ECFV) expanded animals and humans. Since then numerous studies have confirmed the presence of ouabain-like factor(s) (OLF) in blood, urine, cerebrospinal fluid, and various tissues including the heart and hypothalamus. Some of these OLFs represent well-known endogenous compounds, eg, free unsaturated fatty acids, which in vitro exhibit inhibition of transepithelial sodium transport, direct inhibition of the Na-K-ATPase enzyme, displacement of 3H-ouabain from its membrane receptor, and crossreaction with a digoxin antibody. Small molecular weight (MW) OLFs of yet unknown peptidic or nonpeptidic nature, which may be of hypothalamic origin, were also detected in various animal models of hypertension and in hypertensive patients. They may play a pathophysiological role especially in salt- and volume-dependent forms of hypertension. Our results show that OLFs increase basal and vasopressin-stimulated intracellular Ca2+ release in rat vascular smooth muscle cells in culture and in human platelets similar to the newly discovered endothelin. In addition, a natriuretic factor (natriuretic hormone) was detected by bioassay in plasma and urine, whose activity changes in parallel with sodium intake. We found that this natriuretic factor is associated with small peptides with a MW of less than 1,000. It is, however, unlikely that the two biological properties, ie, the ouabain-like and natriuretic activities, reside in a single compound. A number of circulating OLFs is certainly not identical with a humoral natriuretic factor. Nevertheless, there is increasing evidence for multiple interactions between OLF and the atrial natriuretic peptide (ANP).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Endogenous natriuretic and ouabain-like factors. Their roles in body fluid volume and blood pressure regulation. 184 64

Normotensive young men (36 +/- 5 years old) with positive family histories of hypertension (n = 11) and age-matched controls (n = 21) with negative family histories of hypertension were examined. The control group was divided into one group matched for body mass index with those subjects with positive family histories (n = 10) and one group with normal body mass index (n = 11). Blood pressure, central venous pressure (CVP), plasma atrial natriuretic peptide (ANP) and serum aldosterone were examined at a baseline and during an acute volume load with 1000 ml saline solution. Subjects with positive family histories and controls matched for body mass index had a higher blood pressure at baseline than controls with normal body mass index. CVP and serum aldosterone did not differ between the three groups, while sodium intake and plasma concentrations of ANP were significantly higher in subjects with positive family histories. During volume loading, CVP increased significantly more in subjects with positive family histories as compared with the two control groups. A blunted response to ANP was observed during volume loading in subjects with positive family histories, while subjects in the two control groups demonstrated comparable and significant increases in circulating ANP. Serum aldosterone, however, decreased during volume loading in all three groups, with no difference between the groups. We conclude that normotensive subjects with positive family histories are characterized by increased basal concentrations of ANP and exhibit a blunted response to an acute volume load.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Resting and volume-stimulated circulating atrial natriuretic peptide in young normotensive men with positive family histories of hypertension. 184 29


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