Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033036 (APC)
 10,214 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To evaluate the influence of atrial natriuretic factor (ANF) infusion on circulating prorenin, 20 essential hypertensive males, aged between 40 and 60 years, were studied. After 2 weeks under normal sodium intake (120 mmol NaCl per day), patients were randomly assigned to receive either ANF (0.01 fmol/Kg/min) (n.12 patients) or its vehicle (50 mL of isotonic saline) (n.8 patients) over a period of 60 minutes. Blood samples for plasma renin activity (PRA), prorenin and aldosterone (PAC) were taken at time -60, 0, 20, 40, 60, 120, 180, 240 minutes (infusion time: from 0 to 60 minutes). PRA and PAC decreased during the ANF infusion (PRA: from 0.33 +/- 0.05 ng/L/s at time 0 to 0.10 +/- 0.06 ng/L/s at 60 minutes, p < 0.0001; PAC: from 389.2 +/- 99.8 pmol/L at time 0 to 148.7 +/- 44.3 pmol/L at 60 minutes, p < 0.0001), while returned immediately to baseline levels after the infusion was stopped (PRA: 0.37 +/- 0.11 ng/L/s at 180 minutes, PAC: 251.6 +/- 72.1 pmol/L at time 180 minutes). On the contrary, plasma prorenin increased during ANF infusion (from 1.66 +/- 0.58 ng/L/s at time 0 to 2.44 +/- 0.72 ng/L/s at 60 minutes, p < 0.05), and returned to baseline levels after the end of the infusion (1.86 +/- 0.83 ng/L/s at 180 minutes). These data indicate that ANF infusion may alter only the circulating levels of active renin, without affecting plasma prorenin secretion.
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PMID:Effects of atrial natriuretic factor infusion on plasma prorenin levels in hypertensive males. 803 55

The usefulness of the captopril test as a simultaneous screening method for primary aldosteronism (PA) and renovascular hypertension (RVH) was evaluated in 111 patients with essential hypertension, and in 79 patients with secondary hypertension, which included 16 patients with PA and 18 with RVH. Plasma renin activity (PRA, ng/mL/h) and plasma aldosterone concentration (PAC, ng/dL) were determined before and 90 min after administration of 50 mg of captopril in the supine position on a normal NaCl diet. A cutoff point or a discriminant function in the screening was determined by discriminant analysis. A quadratic discriminant function of PRA and PAC after the captopril test identified patients with PA with a false negative rate of 6.3% (1/16), and a false positive rate of 0.6% (1/174) which was significantly lower than that of 3.4% at the basal state (P < .05). In the screening for RVH, the criterion of a postcaptopril PRA of greater than 10.6 ng/mL/h had a false negative rate of 5.6% (1/18) and a false positive rate of 15.1% (26/172). This false positive rate was also significantly lower than that using a criterion for precaptopril PRA of 2.21 ng/mL/h (P < .05). Accordingly, the captopril test was a useful method in the simultaneous screening for PA and RVH, and it may be particularly applicable in specialized hypertension clinics.
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PMID:The usefulness of the captopril test as a simultaneous screening for primary aldosteronism and renovascular hypertension. 830 62

"Non-modulators" are essential hypertensive patients who fail to modulate an adrenal response, renovascular response, or both, to angiotensin II (Ang II). The aim of the present study was to characterize "non-modulators" among Japanese patients with normal-renin essential hypertension and to determine whether non-modulation is related to sodium sensitivity of blood pressure. The increase in plasma aldosterone concentration (PAC response) and the decrease in renal plasma flow (RPF response) in response to Ang II infusion (3 ng/kg/min) were assessed in 15 Japanese patients with essential hypertension who received a high sodium diet (250 mEq/d) followed by a low sodium diet (10 mEq/d). The subjects were divided into two groups (6 modulators and 9 non-modulators) based on their ability to modulate the PAC response during sodium restriction. There was no significant difference between modulators and non-modulators in electrolyte balance or in plasma Ang II levels on either diet. Changes in the PAC response during sodium restriction were significantly correlated with the change in mean blood pressure during sodium restriction (r = -0.67, p < 0.01), while changes in the RPF response were not. RPF responses in both groups decreased during sodium restriction, although an effect on the RPF response in non-modulators was unexpected. These results suggest that non-modulators do exist among Japanese patients, but that this defect does not involve both the adrenal gland and the kidney. Apparently, only non-modulation of the adrenal response is involved in the mechanism of sodium sensitivity.
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PMID:Modulation of target tissue response to angiotensin II and sodium sensitivity in Japanese patients with essential hypertension. 889 41

Plasma angiotensinogen (Ao) concentration (PAC), urinary Ao excretion (UAE), hepatic levels of Ao mRNA and plasma renin concentration (PRC) were studied in control and nephrotic rats subjected to the following treatments: dexamethasone (DEX), ethinyl-estradiol (EE), tri-iodothyronine (T3), bilateral nephrectomy (NX), captopril (CAP) and adrenalectomy (ADX). In nephrotic rats PAC diminished, UAE and PRC augmented and Ao mRNA levels were not altered. In control rats, DEX, EE, T3 and NX increased PAC and Ao mRNA levels whereas CAP diminished PAC but not affected Ao mRNA. ADX diminished PAC and Ao mRNA levels. In nephrotic rats, these treatments produced the same effect than in control rats except in ADX which did not affect PAC. These data suggest that the decreased PAC is not related to alterations in hepatic Ao gene expression but to elevated PRC and UAE.
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PMID:Regulation of hepatic angiotensinogen gene expression in nephrotic rats. 910 41

Pre-eclampsia is characterised physiologically by plasma volume contraction, intravascular coagulation and intense vasoconstriction. It was originally thought that the renin-angiotensin-aldosterone (RAA) system would be overactive but studies have shown a more complex picture. Plasma renin activity (PRA) and concentration (PRC) and plasma angiotensin II (AII) and aldosterone concentrations (PAC) are reduced compared to normal pregnancy. Total renin concentration is normal and plasma concentrations of high molecular weight angiotensinogen are increased in pre-eclampsia though total angiotensinogen is normal. PRA and PRC respond appropriately to physiologic stimuli in pre-eclampsia except for impaired renin release following frusemide, possibly due to prostacyclin deficiency. Although plasma AII concentrations are reduced there is heightened pressor sensitivity to infused AII--the mechanism(s) for this are unknown. PAC is reduced but the ratio PAC-PRC is twofold greater in pre-eclampsia than normal pregnancy. This does not appear to be due to changes in potassium, atrial natriuretic peptide, dopamine or ACTH, and may be another manifestation of increased (adrenal) sensitivity to AII in pre-eclampsia. There is an inverse relationship between the plasma active renin to prorenin ratio and the clinical severity of the pre-eclampsia. Understanding the mechanisms producing these changes in the RAA system in pre-eclampsia will give strong clues to the overall pathogenesis of this disorder.
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PMID:The renin-angiotensin-aldosterone system in pre-eclampsia. 924 50

This study compared the effects of 1 year of monotherapy with a calcium-channel antagonist (nilvadipine; NIL), an angiotensin-converting enzyme (ACE) inhibitor (temocapril; TEM), or a new vasodilator (cadralazine; CAD) on left ventricular (LV) hypertrophy in essential hypertension. Furthermore, to elucidate the mechanism responsible for regression of LV hypertrophy after treatment, LV mass index (LVMI) by echocardiography, plasma renin activity (PRA), aldosterone (PAC), norepinephrine, and atrial natriuretic peptide (ANP) concentration were measured before and after treatment. Thirty-six patients were randomly assigned to the NIL, TEM, or CAD groups. Blood pressure (BP) before treatment was 174 +/- 10/104 +/- 7, 173 +/- 18/103 +/- 8, and 171 +/- 16/103 +/- 7 mm Hg (mean +/- SD) in NIL, TEM, and CAD groups, respectively. BP was lower after treatment with each of the three test drugs than after the placebo period, and there were no differences in BP reduction among three groups. LVMI, in NIL and TEM, was reduced from 129 +/- 48 to 115 +/- 39 g/m2 and from 117 +/- 39 to 88 +/- 20 g/m2 (p < 0.05 and p < 0.01, respectively), whereas, in the CAD group, it was increased (110 +/- 30 to 138 +/- 27 g/m2; p < 0.01). In the CAD group, PAC decreased and ANP increased significantly. The change in LVMI correlated with that in BP for TEM and with that in ANP in all patients. These data indicated that LV volume overload as well as LV pressure overload may contribute to LV hypertrophy and that monotherapy with CAD is not desirable from the point of view of LV mass reduction in essential hypertension.
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PMID:The effects of long-term treatment on left ventricular hypertrophy in patients with essential hypertension: relation to changes in neurohumoral factors. 938 47

To evaluate the pharmacokinetic/pharmacodynamic characteristics of SKP-450, a novel K+ channel opener, a single blind, randomized, placebo-controlled, dose-rising, parallel-group study was conducted in 28 healthy volunteers. The volunteers were randomly allocated to dosage groups of 50 micrograms, 100 micrograms, 200 micrograms, and 300 micrograms. Single doses of SKP-450 were administered orally, after overnight fasting, and serial blood sampling and pharmacodynamic measurements were performed up to 48 hours after the drug was administered. The 200 micrograms group was further studied for food interactions in a crossover fashion. Drug concentrations in plasma were determined by HPLC. Hemodynamic changes after drug administration were evaluated by serial measurements of blood pressure (BP), pulse rate (PR), cardiac index (CI), and total peripheral resistance (TPR), using computerized impedance cardiography. Changes in plasma renin activity (PRA) and aldosterone concentrations (PAC) were determined 4 and 24 hours after drug administration. Both SKP-450 and SKP-818, an active metabolite, showed linear pharmacokinetic characteristics, and food intake did not significantly affect the pharmacokinetic characteristics of either compound. Dose-related pharmacological effects were obvious for both the 200 micrograms and 300 micrograms groups. Hemodynamic parameters related to vasodilation and reflex tachycardia, such as maximum changes in diastolic BP, PR, CI, and TPR, showed significant dose-dependent changes. The area under the time-effect curve (AUEC) of the parameters also showed a similar dose-dependent pattern. The PRA and PAC exhibited significant changes 4 hours after drug administration in the 300 micrograms group. Adverse effects, such as headaches, were more frequently observed at the higher dose levels. SKP-450 was generally well tolerated by these normotensive subjects. The antihypertensive efficacy of SKP-450 needs to be evaluated in hypertensive patients after multiple dosing.
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PMID:Pharmacokinetic/pharmacodynamic evaluation of a novel potassium channel opener, SKP-450, in healthy volunteers. 1088 17

Renal Na+ handling abnormalities have been shown in preascitic cirrhosis. To investigate the underlying pathophysiology, the effects of different sodium intakes on Na(+) balance and renal hemodynamics were assessed at 100 mEq Na+/day (low-sodium diet [LSD]) and after 6 days of 250 mEq Na+/day (high-sodium diet [HSD]). Eight asymptomatic patients with cirrhosis (Pugh-Child A class) (PAC) and 10 healthy controls (CON) were studied. At HSD, although CON readjusted Na+ excretion within the fourth day, PAC did not reach the new balance and developed a final greater Na+ retention (+437 mEq in PAC v +228 mEq in CON, P<.001). In PAC, fractional Na+ excretion (FENa) was significantly lower than in CON at LSD (P<.05), and, after HSD, increased in both groups (P<.05). In PAC, renal vascular resistances (RVR) at LSD resulted lower than in CON (P<.05) and failed to decrease after HSD. As a consequence, after HSD, glomerular filtration rate and renal plasma flow failed to increase in PAC. PRA and plasma aldosterone were significantly lower in PAC, than in CON at LSD (P<.05), and decreased in both groups after HSD (P<.05). Proximal Na+ reabsorption (RProx) [as indicated by fractional free water clearance measured in a state of maximal water diuresis] at LSD was lower in PAC than in CON (P<.05) and decreased in both groups after HSD (P<.05). In summary, early stages of cirrhosis are characterized by: (1) a reduction of RVR, probably associated with splanchnic vasodilation; (2) a Na+ retention already at LSD, as indicated by the lower FENa observed in PAC, that produces extracellular volume (ECV) expansion, with a consequent RProx and renin-angiotensin-aldosterone axis (RAS) suppression; (3) a greater Na+ retention after HSD, associated with an abnormal adaptation of renal hemodynamic, a greater ECV expansion and a consequent Rprox and RAS suppression. These data show the presence of early renal hemodynamic dysfunction in PAC. Our findings also show in this phase of the disease a preserved adaptation of RProx and RAS, thus suggesting that the observed tubular Na+ reabsorption derangement is probably related to abnormal ANP behavior.
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PMID:Sodium retention in preascitic stage of cirrhosis. 1132 May 1

To assess whether an increased production of nitric oxide is involved in the circulatory and renal alterations of cirrhosis, we evaluated systemic hemodynamics (echocardiography), renal hemodynamics, and sodium handling (lithium clearance method), plasma renin activity (PRA), aldosterone (PAC), and norepinephrine in 7 patients (3 men, mean age 65 +/- 2 years) with compensated cirrhosis, portal hypertension, and hyperdynamic circulation during intravenous N(G)-monomethyl-L-arginine (L-NMMA) (3 mg/kg bolus plus 0.05 mg/kg. min for 120 minutes) or placebo (the vehicle) in a randomized, placebo-controlled, crossover study. Administration of L-NMMA resulted in significant reductions in plasma and urinary nitrite levels and plasma cyclic guanosine monophosphate (cGMP), indicating effective inhibition of nitric oxide synthase. L-NMMA also significantly reduced cardiac index (-13%) and increased systemic vascular resistance (+26%), arterial pressure (+9%), renal blood flow (+12%), glomerular filtration rate (+12%), and sodium excretion (+25%). Changes in sodium excretion were caused by both enhanced filtered sodium load and reduced sodium reabsorption in the proximal tubule. Plasma norepinephrine significantly decreased in response to L-NMMA, and there was a trend for reductions in PRA and PAC. Placebo had no appreciable effect on any of the measured parameters. These results indicate that in patients with compensated cirrhosis, portal hypertension and hyperdynamic circulation inhibition of nitric oxide synthase corrects the altered systemic hemodynamics and improves renal function and sodium excretion.
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PMID:Hemodynamic, renal, and endocrine effects of acute inhibition of nitric oxide synthase in compensated cirrhosis. 1143 29

We report a Japanese family with glucocorticoid-remediable aldosteronism (GRA) in whom gene abnormality was identified by the long-polymerase chain reaction (PCR) method. The proband was a 21-year-old female incidentally found to have high blood pressure (173/107 mmHg). Laboratory tests showed hypokalemia (3.7 mmol/l), and high plasma aldosterone concentration (PAC, 234 pg/ml) with suppressed plasma renin activity (PRA, <0.1 ng/ml/h). The circadian rhythm pattern and the results of a rapid adrenocorticotrophic hormone (ACTH) test indicated ACTH-dependent changes in PAC. Imaging studies showed no adrenal mass on either side. A dexamethasone (Dexa) suppression test (1.0 mg/day orally for 7 days) showed a marked decrease of PAC 2 days after administration, and this decreased level was maintained throughout Dexa administration. High blood pressure and hypokalemia also improved during Dexa treatment. The proband's younger sister was 19 years old and had hypertension, PAC of 231 pg/ml, and PRA <0.1 ng/ml/h. The mother was 53 years old and had hypertension, PAC of 98.5 pg/ml, and PRA <0.1 ng/ml/h. The proband's elder sister was a 22-year-old normotensive with PAC of 110 pg/ml and PRA of 0.1 ng/ml. Long-PCR was performed for detection of the chimeric gene associated with GRA, using DNA samples from all four cases and two normal control subjects. Although the aldosterone synthase gene was expressed among all DNA samples, the chimeric gene was detected only in the proband, her younger sister and her mother. Our clinical data and genetic investigation confirmed the presence of GRA in this Japanese family.
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PMID:Japanese family with glucocorticoid-remediable aldosteronism diagnosed by long-polymerase chain reaction. 1167 55


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