Increased plasma vasopressin in low renin essential hypertension

Baseline plasma vasopressin concentrations were measured in 48 men (all 50 years old) with decreased plasma renin concentration and untreated, sustained essential hypertension and in 29 healthy normotensive men. Mean hypertensive plasma vasopressin concentration was more than twice as high as the corresponding normotensive level (15.7 +/- 2.2 [SE] vs 7.5 +/- 1.0 pg/ml; p less than 0.001). Plasma renin concentration in the hypertensive group was reduced compared with that in the normotensive group (0.28 +/- 0.04 vs 0.46 +/- 0.06 Goldblatt units X 10(-4)/ml). These differences appeared despite virtually identical serum osmolality, creatinine clearance, and urinary sodium excretion in the two groups. In the first 38 hypertensive subjects, arterial plasma epinephrine concentrations were significantly increased over those of the first 28 control subjects (99 +/- 12 vs 68 +/- 6 pg/ml; p less than 0.025). In contrast to those with low renin essential hypertension, 35 men with normal renin essential hypertension (all 40 years old) had normal plasma vasopressin levels that were not significantly different from those in a comparable normotensive control group (3.7 +/- 0.8 vs 3.5 +/- 0.4 pg/ml). Arterial epinephrine concentrations were not significantly different between normal renin subjects and the control group. After 6 weeks of treatment with the nonselective beta-adrenergic receptor blocker oxprenolol in 11 subjects with low renin hypertension, blood pressure was reduced and the plasma vasopressin concentration fell from 27.6 +/- 6.4 to 13.5 +/- 4.2 pg/ml (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of aging on human plasma renin: simultaneous multiple assays of enzyme activity and immunoactivity of plasma renin

The effects of aging on plasma renin in normotensive volunteers were evaluated by conventional indirect RIA of angiotensin I and a newly developed direct RIA. Plasma renin activity and the plasma concentration of active renin measured by radiometric assay with monoclonal antibody were significantly lower in 14 subjects over 60 years than in 15 subjects under 60 years (plasma renin activity: 0.5 +/- 0.1 vs 1.7 +/- 0.4 nmol.1-1.h-1, P less than 0.01; plasma active renin: 0.50 +/- 0.05 vs 0.87 +/- 0.13 pmol/l, P less than 0.01, means +/- SEM), whereas neither the total renin activity nor the total plasma renin concentration measured by the newly developed immunometric assay were different in the two groups. In another study, the plasma renin concentration, total renin concentration and immunoreactive total renin concentration measured by direct RIA with polyclonal antibody were determined in 17 young (less than 60 years) and 12 elderly (greater than or equal to 60 years) subjects. Plasma renin concentration was significantly lower in the elderly subjects (1.7 +/- 0.2 nmol.l-1.h-1) than in young subjects (3.2 +/- 0.7 nmol.l-1.h-3, P less than 0.05), but the total renin concentration and immunoreactive total renin concentrations in the two groups were not significantly different. These results indicate that the total renin content of the plasma does not change, whereas the active renin content decreases with age in normal subjects, and suggest that activation of prorenin to active renin may be impaired in elderly subjects.     

Plasma endothelin levels in hypertension and chronic renal failure

Endothelin-1 is a novel endothelium-derived vasoconstrictive peptide. Using a highly specific and sensitive radioimmunoassay for endothelin-1, plasma levels of immunoreactive endothelin-1 were measured in 32 research subjects with normal renal function (21 normal subjects and 11 patients with essential hypertension), 24 patients with nondialyzed chronic renal failure, and 51 patients undergoing maintenance hemodialysis. Although there was no significant difference in plasma immunoreactive endothelin-1 levels among the three groups, patients with essential hypertension had significantly higher plasma endothelin-1 levels than normal subjects (2.29 +/- 1.09 vs. 1.41 +/- 0.50 pg/ml, p less than 0.025). When nondialyzed and hemodialyzed patients were divided into hypertensive and normotensive groups, the nondialyzed hypertensive group (n = 17) had higher plasma endothelin-1 levels than the comparable normotensive group (n = 7) (3.08 +/- 3.43 vs. 0.73 +/- 0.34 pg/ml, p less than 0.05), and the hemodialyzed hypertensive group (n = 18) had higher plasma endothelin-1 levels than the comparable normotensive group (n = 33) (2.66 +/- 1.92 vs. 1.35 +/- 0.73 pg/ml, p less than 0.005). Plasma atrial natriuretic factor, arginine vasopressin, renin activity, and aldosterone concentration did not show significant differences between hypertensive and normotensive individuals or a correlation with plasma endothelin-1 levels. These data suggest that circulating endothelin-1 may be partly involved in the development or maintenance of hypertension in humans.     

Responses of active and inactive plasma renin to insulin-induced hypoglycemia in normal subjects

To examine the in vivo activation mechanism for the conversion of inactive to active renin in human plasma, we measured active, inactive and total plasma renin activity during an insulin tolerance test in normal subjects. Total renin was measured after trypsin activation of inactive renin. Inactive renin was calculated as the difference between total and active renin. With a decrease in the blood glucose level from 92 +/- 8 to 22 +/- 6 mg/dl (p less than 0.01), active renin increased significantly (p less than 0.01) from the basal level of 1.9 +/- 0.6 to 6.0 +/- 1.9 ng/ml.hr at 60 min after insulin injection. Total renin increased and inactive renin decreased slightly, but the changes were not statistically significant. The ratio of active to total renin showed a significant increase (p less than 0.01) at 60 min. These results suggest that stimulation of the endogenous sympathetic nervous system is involved in the in vivo activation of inactive renin.     

Assessment of the renin-angiotensin system in cirrhotic patients. Comparison between plasma renin activity and direct measurement of immunoreactive renin.

The renin-angiotensin system plays an important physiological role and has prognostic significance in cirrhotics with ascites. The degree of stimulation of this system is usually estimated by measuring plasma renin activity after incubation periods of 2-3 h. Recent investigations showed that the direct measurement of immunoreactive renin also estimates the degree of activity of the system. In this study, immunoreactive renin and plasma renin activity (measured at incubation periods of 10, 20, 50 and 180 min) were determined in ten healthy subjects, five hyperreninemic non-hepatic patients and 47 cirrhotics with ascites. Cirrhotic patients showed significantly higher plasma renin activity (5.1 +/- 0.9 ng/ml per h, p less than 0.05) and immunoreactive renin (145.4 +/- 24.4 pg/ml, p less than 0.01) than healthy subjects (1.2 +/- 0.15 ng/ml per h and 25.1 +/- 1.1 pg/ml, respectively). The angiotensin I generation rate was constant during the 3-h incubation in 22 cirrhotics and a close relationship (r = 0.956, p less than 0.001) between plasma renin activity (3.5 +/- 1.6 ng/ml per h) and immunoreactive renin (71 +/- 25 pg/ml) was observed in these patients. In the remaining 25 cirrhotics the generation rate of angiotensin I declined with time and the calculated plasma renin activity at 180 min was lower than the activity calculated at 10 min by 50.7%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of renin inhibition in systemic hypertension

The effect of the direct renin inhibitor enalkiren (Abbott Laboratories) was examined in 8 healthy patients with essential hypertension. With an unrestricted sodium diet, plasma renin concentration was inhibited within 10 minutes by intravenous enalkiren and remained essentially undetectable for greater than or equal to 6 hours (11.9 +/- 4 to 1.0 +/- 0.6 ng angiotensin I/ml/hour, p less than 0.05). Mean arterial blood pressure declined gradually (108 +/- 5 to 84 +/- 4 mm Hg, p = 0.02), as did plasma aldosterone concentration (14.4 +/- 3.8 to 4.4 +/- 0.8 ng/dl, p = 0.03), whereas plasma immunoreactive active renin concentration increased progressively (35 +/- 14 to 160 +/- 60 pg/ml, p greater than 0.05). Urinary excretion of the stable metabolite of prostacyclin (6-keto-prostaglandin F1 alpha) decreased slightly, but not significantly (42 +/- 10 to 33 +/- 11 ng/g creatinine, p = 0.13). The addition of a diuretic decreased baseline blood pressure and increased baseline plasma renin and aldosterone values. Blood pressure responses to enalkiren were slightly (though not significantly) greater than those observed before diuretic administration. We conclude that enalkiren is effective in decreasing blood pressure and in inhibiting the renin system, without significantly altering urinary prostacyclin excretion, in patients with essential hypertension. These results suggest that the renin system contributes to the maintenance of elevated blood pressure in some patients with essential hypertension.     

Similarity between active and trypsin-activated inactive renin in dog plasma by means of renin inhibition: the dog as an animal model for studies of inactive renin

A method for trypsin-activation of dog plasma inactive renin is described. Liquid phase trypsin (final concentration 6.7 mg/ml) was used and the reaction was stopped after 2 min at 4 degrees C by soybean trypsin inhibitor (13 mg/ml). Renin was measured as angiotensin I (Ang I) generation in trypsin-treated and untreated plasma using the antibody-trapping method, in the presence of excess ox renin substrate. The renin-like activity after trypsin was indeed due to renin, since Ang I generation in dog plasma before and after trypsin treatment was completely inhibited by H-77 at 10(-6) mol/l, and the two IC50 values were very similar (2.7 +/- 0.7 and 2.9 +/- 0.7 at 10(-8) mol/l, respectively). Dog plasma inactive renin was effectively separated from active renin by chromatography on Affigel Blue. Like human prorenin, dog plasma inactive renin rose in response to sodium depletion (furosemide 5 mg/kg, i.v.) followed by a low-salt diet (1 mmol Na+/day) for 4 days, (from 29.6 +/- 8 to 162 +/- 22 microU/ml; P less than 0.01, n = 10). Active renin also increased as expected. Intravenous captopril (6 mg/kg per h), for 3 h, led to a sharp increase in dog plasma active renin (from 53 +/- 8 to 360 +/- 60 microU/ml; P less than 0.01, n = 6), whereas inactive renin remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)     

Renin release regulation during acute renin inhibition in normal volunteers

Blockade of the renin-angiotensin system by an angiotensin converting enzyme (ACE) inhibitor or an angiotensin II (Ang II) antagonist is accompanied by a reactive rise in renin release. This rise is generally attributed to interruption of the short feedback loop between Ang II and renin release. Similarly, after the administration of a renin inhibitor, the plasma concentrations of active and total renin are increased and plasma renin activity is suppressed. The aim of the present study was to investigate if a fall in the plasma Ang II level is the unique determinant of the rise in the active renin (AR) level that follows renin inhibition. Six normal male volunteers participated in three successive 240-minute experiments at weekly intervals according to a single-blind randomized Latin square design. For experiment 1, Ang II was infused at 2 ng/kg/min from 0 to 60 minutes and at 4 ng/kg/min from 60 to 120 minutes. For experiment 2, 0.3 mg/kg of the new potent renin inhibitor Ro 42-5892 was injected at 30 minutes followed by infusion at 0.1 mg/kg/hr from 30 to 240 minutes. For experiment 3, Ang II and Ro 42-5892 were administered simultaneously at the same doses as described above. The mean +/- SEM Ang II concentration increased from 10.2 +/- 1.6 to 33.7 +/- 11.2 pg/ml after infusion of exogenous peptide. It decreased from 9.5 +/- 0.9 to 1.4 +/- 0.3 pg/ml after the injection of Ro 42-5892 and increased from 15.6 +/- 2.9 to 37.1 +/- 11.8 pg/ml after the simultaneous infusion of both compounds.(ABSTRACT TRUNCATED AT 250 WORDS)     

Blocking T-type Ca2+ channels with efonidipine decreased plasma aldosterone concentration in healthy volunteers.

Efonidipine can block both L- and T- type Ca2+ channels. In a previous in vitro study, we clarified that efonidipine dramatically suppresses aldosterone secretion from human adrenocortical tumor cells during angiotensin II (Ang II)- and K+-stimulation, whereas nifedipine, a dominant L-type Ca2+ channel antagonist, does not. This study was conducted to assess the in vivo effects of efonidipine and nilvadipine on the plasma aldosterone concentration. Placebo, 40 mg of efonidipine, or 2 mg of nilvadipine was administered to five healthy male volunteers. Hemodynamic parameters (pulse rate [PR] and blood pressure [BP]), plasma concentrations of neurohormonal factors (plasma renin activity, Ang II, aldosterone, and adrenocorticotropic hormone [ACTH]), and serum concentrations of Na+ and K+ were measured before and 6 h after administration of the agents. All three agents had little effect on PR and BP. Efonidipine and nilvadipine significantly increased plasma renin activity and Ang II. Both had little effect on ACTH, Na+, and K+. The plasma aldosterone concentration was significantly decreased after efonidipine treatment (88.3 +/- 21.3 to 81.6 +/- 24.9 pg/ml, p = 0.0407), whereas it was significantly increased after nilvadipine treatment (66.5 +/- 12.2 to 82.17 +/- 16.6 pg/ml, p = 0.0049). Placebo had little effect on neurohormonal factors. Efonidipine decreased plasma aldosterone concentration despite the increase in plasma renin activity and Ang II, suggesting that T-type Ca2+ channels may also play an essential role in the secretion of aldosterone in healthy human volunteers.     

Dissociation of the prostaglandin and renin angiotensin systems during captopril therapy for chronic congestive heart failure secondary to coronary artery disease

Neurohumoral systems are activated as compensatory mechanisms in congestive heart failure (CHF). A close correlation has been reported between the renin angiotensin and prostaglandin systems in CHF. Furthermore, serum sodium concentration provided an excellent index of hormonal status. In this study, these relations were examined after acute and chronic blockade of renin angiotensin system with captopril. Eight patients with advanced CHF (New York Heart Association III or IV) were studied. Before captopril treatment, all hormone levels were elevated. Mean plasma renin activity was 24 +/- 7 ng Al/ml/hour, angiotensin concentration was 221 +/- 11 pg/ml and aldosterone concentration was 82 +/- 17 pg/ml. Plasma PGE2 metabolite was 1,425 +/- 321 pg/ml. A close correlation was observed between plasma angiotensin II and PGE2 metabolite levels (r = 0.7); inverse correlations existed between serum sodium concentration and PGE2 metabolite levels (r = -0.9) and with plasma renin activity (r = -0.6). Captopril therapy reduced the plasma angiotensin II level to 38 +/- 6 pg/ml and aldosterone concentration to 15 +/- 3 pg/ml, but did not affect plasma renin activity (31 +/- 10 ng Al/ml/hour) when measured in 1 week. Paradoxically, PGE2-metabolite levels increased further (to 3,031 +/- 346 pg/ml) despite blockade of the renin angiotensin system. Serum sodium concentration no longer correlated with hormone levels. These effects were sustained at 2 months of follow-up. Thus, captopril caused a dissociation between the renin angiotensin system and prostaglandin. The activation of prostaglandin is probably due to captopril's effect on prostaglandin biosynthesis and may contribute to captopril's sustained efficacy in CHF.     

Immunoreactive renin, prorenin, and enzymatically active renin in plasma during pregnancy and in women taking oral contraceptives

Direct RIA of renin with monoclonal renin antibodies and indirect RIA with angiotensin I antibodies were performed in plasma of 44 pregnant women, 44 women taking an oral contraceptive (OC), and 54 normal women. The following parameters were measured: immunoreactive renin, naturally occurring enzymatically active renin (active renin), trypsin-activatable inactive renin (prorenin), PRA, and renin substrate. Immunoreactive renin (mean, 95% confidence interval) was significantly higher in pregnant women (1090; 420-2800 pg/ml; third trimester) than in normal women (248; 101-562 pg/ml; P less than 0.001) and was lower in OC-treated women (131; 41-415 pg/ml; P less than 0.001). Prorenin and active renin also were increased in pregnant women and decreased in OC-treated women. The fraction of renin that was in the active form was lower in pregnant women (4.8; 1.4-18%) than in OC-treated women (8.8; 3.0-25%; P less than 0.001) and normal women (9.1; 2.9-29%; P less than 0.001). Renin substrate was increased to comparable levels in pregnant women and OC-treated women, but PRA was increased in pregnant women and normal in OC-treated women. The maximum velocity per unit weight of renin was the same for active renal renin as for active plasma renin and trypsin-activated plasma prorenin. Maximum velocity and Km values measured in mixtures of purified active renin and renin substrate and the concentrations of active renin and renin substrate measured in whole plasma were entered into the Michaelis-Menten equation for calculating PRA. The calculated values were similar to the measured results in all three groups, indicating that PRA was determined by the molar concentrations of enzyme and substrate. Thus, we found no evidence of unknown substances in plasma interfering with the enzyme-substrate reaction. The percentage of circulating renin in the active form was much lower during pregnancy than in other conditions where the renal release of active renin is stimulated and prorenin is as high as during pregnancy. This suggests that a smaller fraction of prorenin is intrarenally converted into active renin before its release into the circulation or that a larger fraction of circulating prorenin is of extrarenal origin. The finding that PRA is normal during OC treatment suggests that the estrogen-induced increase in renin substrate is compensated for by suppressed renal release of active renin.     

Ratio of serum aldosterone to plasma renin concentration in essential hypertension and primary aldosteronism.

The ratio of serum aldosterone to plasma renin activity (PRA) has been proposed as sensitive screening method in the diagnosis of primary aldosteronism under random conditions. However, the method for determination of renin activity is hampered by the necessity of ice cooling during storage and transport. The present study was therefore conducted to examine the ratio of serum aldosterone to plasma renin concentration (ARR) and its usefulness in diagnosis of primary aldosteronism under ambulatory conditions and given antihypertensive medication. 146 patients with arterial hypertension who consecutively attended the outpatient clinic were studied prospectively. Patients with secondary hypertension besides primary aldosteronism were not included in the series. 37 normotensive patients served as control. Also, 17 patients with known primary aldosteronism were retrospectively examined. Among the hypertensive group 2 patients with Conn's syndrome were newly detected (1.4%). ARR was 7.92 +/- 6.04 [pg/ml]/[pg/ml] in normotensive controls (range from 2.03 to 26.98), 14.61 +/- 18.50 [pg/ml]/[pg/ml] in patients with essential hypertension (n = 144, range from 0.41 to 115.45) and 155.92 +/- 127.84 [pg/ml]/[pg/ml] in patients with primary aldosteronism (n = 19, range from 6.75 to 515). 17 of the 19 patients with Conn's syndrome had an ARR of more than 50. Under ongoing drug treatment this represents a sensitivity of 89% and a specificity of 96%. Sensitivity decreased to 84% and specificity increased to 100% when a second criteria (aldosterone > or = 200 pg/ml) was included. In summary, ARR using renin concentration is a useful screening parameter for primary aldosteronism.     

Increased production of vascular endothelial growth factor by peripheral blood mononuclear cells in patients with inflammatory bowel disease

BACKGROUND: Vascular endothelial growth factor (VEGF) is a potent angiogenic, vascular permeability-enhancing cytokine with overexpression in various pathological disorders, including tumour growth, chronic inflammation and tissue repair. Recent studies have shown significantly increased serum levels of VEGF in patients with inflammatory bowel disease. The origin of the circulating VEGF is still unknown. The present investigation examines the VEGF production by peripheral blood mononuclear cells (PBMCs) in patients with inflammatory bowel disease. METHODS: VEGF levels were measured in culture supernatants of unstimulated PBMCs of 27 patients with inflammatory bowel disease and 10 healthy volunteers using a solid phase ELISA. In addition, VEGF serum levels were determined. RESULTS: PBMCs of both active Crohn's disease patients (1142.6+/-483.9 pg/ml, P < 0.001, n = 12) and active ulcerative colitis patients (748.0+/-637.6 pg/ml, P = 0.006, n = 4) produced significantly higher amounts of VEGF compared with PBMCs of healthy volunteers (113.4+/-101.8 pg/ml, n = 10). In addition, there was a significantly increased VEGF production by PBMCs of patients with active disease compared with PBMCs of patients with quiescent Crohn's disease (261.6+/-254.8 pg/ml, P < 0.001, n = 7) and inactive ulcerative colitis (147.7+/-100.3 pg/ml, P = 0.02, n = 4). There was no significant difference in VEGF release between patients with inactive inflammatory bowel disease and healthy controls. CONCLUSIONS: Significantly increased VEGF production by PBMCs was found in patients with active Crohn's disease and active ulcerative colitis. The study helps to clarify one of the origins of the significantly enhanced VEGF serum levels in patients with active inflammatory bowel disease observed in recent studies.     

Aspirin lowers blood pressure in patients with renovascular hypertension

To clarify the role of renal prostanoid in hyperreninemia and high blood pressure in human renovascular hypertension, we measured prostaglandin E2 and renin activity in renal venous and abdominal aortic plasma before and after the intravenous administration of the cyclooxygenase inhibitor, aspirin DL-lysine. Subjects were six patients with unilateral renovascular hypertension and six with essential hypertension. In patients with renovascular hypertension, prostaglandin E2 concentration in renal venous plasma from the stenotic kidney was 9.25 +/- 1.48 pg/ml, which was significantly higher (p less than 0.01) than the concentration in the renal venous plasma from the normal kidney (4.97 +/- 1.02 pg/ml) or in the aortic plasma (2.59 +/- 0.15 pg/ml). Plasma renin activity was also higher in the renal vein of the stenotic kidney than in the other two sites. The stenotic side/normal side ratio of the renal venous prostaglandin E2 correlated significantly with a renin ratio greater than 1.5 (r = 0.8211, p less than 0.05). Intravenous injection of aspirin DL-lysine (18 mg/kg) 30 minutes later markedly suppressed prostaglandin E2 and renin levels at all sites and clearly lowered arterial blood pressure (mean: from 120 +/- 6 to 110 +/- 5 mm Hg, p less than 0.01). The reduction in blood pressure correlated significantly with the suppression of plasma renin activity in the aorta (p less than 0.05) and in the renal vein of the stenotic kidney (p less than 0.01). Conversely, in patients with essential hypertension, aspirin had little effect on renin levels and increased mean blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Neurohumoral consequences of vasodilator therapy with hydralazine and nifedipine in severe congestive heart failure

We evaluated the effects of intravenous hydralazine (5 to 30 mg) and oral nifedipine (20 to 80 mg) on plasma catecholamines, renin, and aldosterone in 18 patients with severe chronic heart failure. Both drugs resulted in a significant decrease in systemic vascular resistance and mean systemic blood pressure, and led to an increase in cardiac output. Baseline plasma norepinephrine concentration was elevated in most patients; however, augmentation of cardiac output with both drugs did not decrease the values of this hormone (from 870 +/- 128 to 946 +/- 161 pg/ml with hydralazine and from 1088 +/- 260 to 1106 +/- 187 pg/ml with nifedipine). Plasma epinephrine level was also elevated at baseline and did not change significantly following nifedipine therapy (164 +/- 44 vs 199 +/- 54 pg/ml), but increased in most patients following the administration of hydralazine (from 105 +/- 45 to 153 +/- 27 pg/ml, p less than 0.01). The renin-aldosterone system was activated in our patients and also demonstrated a different response to both drugs. Hydralazine therapy did not change either the plasma renin concentration (30 +/- 7 vs 28 +/- 7 ng/ml/hr) or the aldosterone level (24 +/- 7 vs 22 +/- 5 ng/dl). In contrast, nifedipine increased the plasma renin concentration (22 +/- 7 to 29 +/- 8 ng/ml/hr, p less than 0.05). This change did not correlate with changes in systemic blood pressure (r = 0.03) and was probably the result of previously shown calcium blockade-mediated stimulation of renin release from the juxtaglomerular cells of the kidney.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma adrenomedullin concentrations in patients with renovascular or malignant hypertension

AIM: The aim of the present study was to investigate the behaviour of plasma adrenomedullin (AM), a hypotensive peptide, in patients with malignant (MHT) and renovascular hypertension (RVH), 2 pathologic conditions in which renin-angiotensin system (RAS) is activated and to compare them with those in essential hypertensive patients (EHT) and normotensive subjects (NS). METHODS: Three groups of hypertensive patients have been studied: group 1 (4 patients with MHT), group 2 (10 patients with RVH), group 3 (24 patients with EHT) and 21 patients NS were enrolled as controls. In all patients, 10 ml vein blood samples were collected and AM was measured with specific radioimmunoassay. RESULTS: As expected, the plasma renin activity (PRA) levels in the RVH and MHT patients were significantly higher (p<0.0001) respect to NS and EHT. The mean plasma AM (+/-SD) concentrations in EHT (22.5+/-9.1 pg/ml) and RVH (46.8+/-19.4 pg/ml) were significantly (p<0.0001) higher than those in NS (13.7+/-6.1 pg/ml). The plasma AM concentrations were further elevated in MHT patients (107+/-12.3 pg/ml) and were significantly higher (p<0.0001) than those in EHT and RVH patients. In the MHT patients the elevated plasma AM levels, similarly to blood pressure and PRA values, declined after antihypertensive treatment (36.8+/-5.7 pg/ml; p<0.01). CONCLUSION: In conclusion, the findings demonstrated that the plasma AM concentrations were increased in proportion to the severity of arterial hypertension. RAS was activated in patients with MHT and RVH suggesting that activation of this system may contribute to increased in the plasma levels of AM.     

Immunoreactive corticotropin-releasing hormone in human plasma during pregnancy, labor, and delivery

We previously reported that immunoreactive corticotropin-releasing hormone (CRH) is present in human placenta and third trimester maternal plasma, and that such material is very similar to rat CRH and the predicted structure of human CRH. We suggested that maternal plasma immunoreactive CRH may be of placental origin. To further investigate this possibility, we measured plasma immunoreactive CRH in women during pregnancy, labor, and delivery and 1 and 2 h postpartum, and in nonpregnant women. Umbilical cord plasma and placental CRH concentrations were also measured. In the first trimester of pregnancy, the mean maternal plasma level was 5.9 +/- 1.0 pg (+/- SEM)/ml (n = 24), not significantly different from that in 10 nonpregnant women (5.8 +/- 0.8 pg/ml). Plasma CRH concentrations progressively increased during pregnancy (second trimester, 35.4 +/- 5.9 pg/ml (n = 39); early third trimester (28-34 weeks), 263 +/- 41 pg/ml (n = 14); late third trimester (35-40 weeks), 800 +/- 163 pg/ml (n = 20)]. There was a significant correlation between maternal plasma CRH levels and weeks of pregnancy. Plasma CRH concentrations were further elevated (2215 +/- 329 pg/ml; n = 9). During early labor, peaked at delivery (4409 +/- 591 pg/ml; n = 28), and declined rapidly after delivery [1 h postpartum, 1042 +/- (353 pg/ml (n = 13); 2 h postpartum, 346 +/- 91 pg/ml (n = 13)]. There was a significant correlation (r = 0.562; P less than 0.01) between matched maternal plasma and placental CRH concentrations. The mean umbilical cord plasma CRH level (50.6 +/- 6.1 pg/ml; n = 28) was much lower than that in the mother at the time of delivery. Umbilical venous plasma CRH levels were significantly greater than those in simultaneously obtained umbilical arterial plasma (70.8 +/- 11.3 and 41.8 +/- 4.9 pg/ml, respectively; n = 11). There was a significant correlation (r = 0.384; P less than 0.05) between maternal and fetal CRH concentrations. Gel filtration of plasma obtained from women during the third trimester, at delivery, and early postpartum and placental extracts revealed two major peaks of immunoreactive CRH: a high mol wt peak and one at the elution position of rat CRH. In contrast, only rat CRH-sized material was detected in plasma from nonpregnant women and umbilical cord plasma. Maternal plasma immunoreactive CRH-sized material stimulated ACTH release from anterior pituitary tissue in a dose-dependent manner and was equipotent with rat CRH.(ABSTRACT TRUNCATED AT 400 WORDS)     

Exaggerated secretion of atrial natriuretic polypeptide during dynamic exercise in patients with essential hypertension

The plasma concentration of atrial natriuretic polypeptide (ANP) was measured in nine patients with essential hypertension during two grades of exercise tests performed in the supine position on a bicycle ergometer. The plasma ANP concentration significantly increased from 97.0 +/- 19.2 pg/ml to 107.6 +/- 23.7 pg/ml (p less than 0.05) during low-grade exercise (50% of the maximal heart rate) and from 96.2 +/- 16.5 pg to 192.8 +/- 30.7 pg/ml (p less than 0.01) during high-grade exercise (75% of the maximal heart rate). During high-grade exercise plasma epinephrine and norepinephrine concentrations showed significant increases. The plasma ANP concentration was significantly correlated with systolic blood pressure (r = 0.51; p less than 0.05). Patients with essential hypertension showed greater absolute increases in the plasma ANP concentration and systolic blood pressure during exercise compared to normotensive subjects. These results suggest that exercise stimulates secretion of ANP in response to its intensity in patients with essential hypertension and that a greater rise in atrial pressure, resulting from a greater elevation of systolic blood pressure, may be involved in the exaggerated secretion of ANP in patients with essential hypertension.     

Distribution of plasma glucagon immunoreactivity in a patient with suspected glucagonoma.

Gel filtration of plasma from a patient with a clinical syndrome of glucagonoma and a total plasma glucagon level of 2600 pg/ml, revealed the four glucagon immunoreactive fractions found in normal subjects. The total hyperglucagonemia observed was due to high levels of true glucagon and proglucagon moieties. The so-called "big plasma glucagon" (BPG) measured 190 pg/ml (normal average 113 +/- 79 pg/ml, Mean +/- SD, N = 10); the large glucagon immunoreactivity, LGI (9000 mol wt), measured 625 pg/ml (normal average 11 +/- 16 pg/ml); the true glucagon accounted for 1435 pg/ml (normal average 31 +/- 29 pg/ml); and the small glucagon immunoreactive fraction (approximately 2000 mol wt) measured 35 pg/ml (normal average 26 +/- 18 pg/ml). The high levels of LGI, considered a candidate for proglucagon, may reflect the increased secretory activity of the tumor.     

Prognostic importance of atrial natriuretic peptide in patients with chronic heart failure

Several circulating neurohormones have been shown to have prognostic significance in patients with chronic heart failure, but the relation between plasma levels of atrial natriuretic peptide and mortality in this disorder remains unknown. Plasma levels of immunoreactive atrial natriuretic peptide were measured in 102 patients in whom left ventricular ejection fraction, ventricular arrhythmias on ambulatory electrocardiographic recording and plasma levels of norepinephrine, renin activity, aldosterone and arginine vasopressin were also measured. Compared with patients with atrial natriuretic peptide concentrations below the median value of 125 pg/ml, patients with higher levels of the peptide had a higher plasma renin activity (8.9 +/- 1.8 versus 2.6 +/- 0.4 ng/ml per h) and plasma norepinephrine (858 +/- 116 versus 538 +/- 45 pg/ml), more frequent premature ventricular depolarizations (4,485 +/- 715 versus 2,004 +/- 495/day) and more advanced hemodynamic abnormalities (all p less than 0.05). During the subsequent 13 to 25 months of follow-up, patients with high levels of atrial natriuretic peptide had a significantly lower rate of survival than did those whose initial circulating peptide concentrations were normal or mildly increased (p = 0.01). These data indicate that, in patients with chronic heart failure, plasma atrial natriuretic peptide provides important prognostic information. This may relate to the ability of the hormone to reflect the interplay of several pathophysiologic factors that contribute to mortality in this disease.