Abnormal glomerular and tubular response to intravenous frusemide in patients with chronic glomerulonephritis

Fourteen normotensive patients with chronic glomerulonephritis and well-preserved renal function and thirteen healthy control subjects were studied. Glomerular filtration rate (GFR), proximal and distal absolute and fractional tubular reabsorption (PAR, PFR, DARNa, DFRNa), evaluated by the lithium clearance technique, were determined before and in four 30-60-min periods after intravenous injection of frusemide 0.5 mg/kg body weight (Study 1) and 1.0 mg/kg body weight (Study 2). Plasma concentrations of angiotensin II (Ang II), aldosterone (Aldo), atrial natriuretic peptide (ANP) and arginine vasopressine (AVP) were measured before, and 60 and 180 min after frusemide. GFR decreased and UNa and FENa increased significantly in patients and controls after frusemide in both studies, but in study 2 GFR decreased significantly more in patients than in controls, and UNa and FENa increased significantly less above baseline in patients compared to controls. PAR, PFR, DARNa, and DFRNa were reduced in patients and controls in both studies. In study 2 the reduction in PAR was significantly (P less than 0.05) less pronounced in patients (23%) than in controls (43%), whereas DARNa was reduced significantly more (P less than 0.05) in patients (36%) than in controls (21%). The efficiency of frusemide with regard to renal sodium excretion was significantly reduced in patients compared to controls in both studies. Angiotensin II and aldosterone increased, ANP decreased, and AVP was unchanged in patients and controls in both studies. It is concluded that in comparison to control subjects, patients with chronic glomerulonephritis and well-preserved GFR respond to frusemide with an exaggerated reduction in GFR, a lesser decrease in absolute proximal tubular reabsorption, and a larger reduction in absolute distal tubular reabsorption. Thus, primary glomerular disease with well-preserved glomerular function may be accompanied by a distinctly disturbed tubular function.     

Effect of frusemide on atrial natriuretic peptide, guanosine cyclic monophosphate, angiotensin II, aldosterone, vasopressin, prostaglandin E2 and blood volume in the nephrotic syndrome.

Blood volume, plasma concentrations of atrial natriuretic peptide, guanosine cyclic monophosphate (cGMP), angiotensin II, aldosterone and arginine vasopressin, and urinary excretion rate of prostaglandin E2, cGMP, sodium, and water were determined before and after intravenous administration of frusemide 0.75 mg/kg body-weight in nine patients with the nephrotic syndrome and 15 control subjects. The decrease in blood volume and the increase in urinary sodium and water excretion after fusemide were significantly reduced in the nephrotic patients compared with the controls. Atrial natriuretic peptide was reduced after frusemide both in patients (6.2 to 4.9 pmol/l, medians, P less than 0.05) and controls (5.9 to 4.8 pmol/l, P less than 0.01), but the nadir was delayed in the patients, and cGMP in plasma and urine was reduced only in the controls. The angiotensin II increase was delayed in the patients and aldosterone increased only in the controls. Basal urinary excretion of prostaglandin E2 was less in the nephrotic patients than in the controls (P less than 0.05), but after frusemide the prostaglandin E2 excretion rate increased in the patients (0.25 to 0.62 pmol/min, P less than 0.05), but not in the controls (0.46 to 0.39 pmol/min). In conclusion, reduced water and sodium excretion after frusemide in the nephrotic syndrome is accompanied by a diminished reduction of blood volume, a delayed decrease in atrial natriuretic peptide, and a blunted increase in angiotensin II and aldosterone compared with healthy subjects. Sodium excretion after frusemide may be more dependent on PGE2 production in nephrotic patients than in healthy subjects.     

Change in renal tubular sodium and water handling during progression of polycystic kidney disease: relationship to atrial natriuretic peptide

Renal tubular sodium and water handling determined by the lithium clearance technique, plasma concentrations of atrial natriuretic peptide (ANP), angiotensin II, aldosterone, arginine vasopressin (AVP), and urinary excretion of prostaglandin E2 (PGE2) were determined both during basal conditions and before and after intravenous sodium loading with a 2.5% sodium chloride solution in patients with polycystic kidney disease (PKD), ten with normal or slightly reduced kidney function (PKDN) and seven with moderately reduced kidney function (PKDR), and in 15 healthy controls. In PKDN tubular function was normal, whereas in PKDR both proximal and distal reabsorption of sodium and water were reduced. Angiotensin II and aldosterone were normal in both groups of patients. During basal conditions ANP was higher in PKDR than in PKDN. PGE2 was significantly higher in PKDR than in PKDN. For all patients significant correlations were found between GFR and both ANP (rho = -0.51, n = 17, P less than 0.05) and PGE2 (rho = -0.53, n = 17, P less than 0.05). It is concluded that renal sodium handling is normal in the early stages of PKD. With deterioration of kidney function both proximal and distal tubular reabsorption of sodium is reduced and the accompanying changes in ANP and PGE2 may be compensatory phenomena counteracting declining glomerular filtration rate.     

Renal haemodynamic changes, renal tubular function, sodium and water homeostatic hormones in patients with chronic glomerulonephritis and in healthy humans after intravenous infusion of amino acids

To determine whether renal reserve capacity was preserved inpatients with chronic glomerulonephritis with well-preservedkidney function, and how sodium was handled in proximal anddistal tubules, 13 healthy control subjects and 13 patientswith biopsy-verified chronic glomerulonephritis were studiedbefore and during a continous 120-min amino-acid infusion. Glomerularfiltration rate (GFR), renal plasma flow (RPF), and tubularfunction evaluated by the lithium clearance method, were determinedduring six clear ance periods of 30 min each. Plasma concentrationsof angiotensin II, atrial natriuretic peptide (ANP), aldosterone,arginine vasopressin (AVP), glucagon, amino acid and serum osmolalitywere determined before, 60, and 120 min after infusion. GFRand RPF increased about 10% in both groups; filtration fraction(FF) was unchanged. Proximal tubular reabsorption of sodiumand water decreased, and distal tubular reabsorption of sodiumand water increased, and thus the net excretion of sodium andwater was unchanged. Angiotensin II and aldosterone were reducedin control subjects, but not in the patients. ANP and glucagonincreased equally in both groups. Most amino acids increasedtwo- or threefold. It is concluded that renal reserve capacityand glomerulotubular balance are intact in patients with chronicglomerulonephritis with well-preserved renal function, but thereis an abnormal lack of suppression of the renin-angiotensin-aldosteronesystem in response to an amino acid infusion in these patients.     

Effect of two regimens of intravenous amino acid infusion on renal haemodynamics, renal tubular function and sodium and water homeostatic hormones in healthy humans

The effect of two different regimens of intravenous infusion of amino acids on glomerular filtration rate (GFR), renal plasma flow (RPF), tubular sodium and water handling judged from the clearance of lithium (CLi), and plasma concentrations of angiotensin II (Ang II), aldosterone (Aldo), arginine vasopressin (AVP), atrial natriuretic peptide (ANP), growth hormone (GH), and glucagon was investigated in healthy humans. In the first protocol (n = 11) the infusion lasted 90 min; both GFR and RPF increased significantly (median increase 7.1% and 9.1% respectively, P less than 0.05 both). In the second protocol (n = 13) the infusion lasted 30 min; both GFR and RPF tended to increase (median increase 3.5% and 7.4%) but the change did not reach significance. The changes in tubular sodium and water handling were similar in the two protocols. Absolute reabsorption rates in the proximal tubules were unaltered, resulting in an increased output into the distal tubules that was totally compensated for by an increased distal reabsorption. Thus no changes in urinary excretion of sodium and water were observed. Ang II, Aldo, AVP, ANP and GH were unchanged by amino acid infusion, but glucagon increased. It is suggested that the alterations in renal haemodynamics and distal tubular reabsorption may be mediated by glucagon.     

Do opioid receptors participate in the regulation of atrial natriuretic peptide (ANP) secretion in hypertensive patients?

Experimental and clinical studies seem to prove that both endogenous opioids and atrial natriuretic peptide (ANP) are involved in blood pressure regulation. This raised the question, whether these two factors are functionally interrelated to each other. We tried to answer this question by assessing plasma ANP levels in 15 patients with II degrees essential hypertension and in 15 healthy subjects under water immersion (WI) conditions. In all subjects two WI tests were performed--one without pretreatment with naloxone, and a second one after blockade of opioid receptors by this opioid receptor antagonist. Parallel to ANP, plasma renin activity (PRA), aldosterone (ALD) and vasopressin (AVP) were assessed. In hypertensive patients significantly higher basal plasma ANP levels were found than in control subjects. WI induced a significant increase of plasma ANP in both examined groups which became markedly reduced after blockade of opioid receptors by naloxone. Naloxone did not influence the WI induced decrease of PRA, ALD and AVP respectively. From results presented in this study we conclude, that a.) opioid receptors seem to influence regulation of ANP secretion both in healthy normotensive subjects and patients with essential hypertension, and b.) that WI induced alterations of ANP on the one side and of PRA, ALD and AVP on the other side are not interrelated.     

Altered vasopressin release and osmotic regulation during exercise in patients with pyelonephritic renal scarring

Children and adults with pyelonephritic renal scarring are at high risk of developing hypertension. The objectives of the present investigation were to study if it is possible to detect early disturbances in blood pressure (BP) control and secretion of hormones involved in the regulation of BP and renal function, in patients with renal scarring. We studied renal function at rest, BP regulating hormones and BP at rest and during graded bicycle exercise until exhaustion. The 22 patients with renal scarring had significantly lower glomerular filtration rate and renal blood flow than the 13 healthy age-matched controls. At rest, the patients had higher diastolic (p less than 0.01) and mean arterial BP (p less than 0.02), higher plasma renin (p = 0.06) and higher serum osmolality (p less than 0.001) but there were no significant differences in systolic BP, angiotensin II, aldosterone or vasopressin (AVP). The patients with renal scarring had higher AVP than the controls during light and moderate exercise and 15 min after maximal exercise. BP and renal hormones increased significantly but similarly during exercise in both patients and controls. There were no significant differences in BP control or release of pressure-regulating hormones at maximal exercise. Maximal exercise did not evoke pathological BP response in normotensive young adults with pyelonephritic renal scarring. The increase in serum osmolality and hypersecretion of AVP during light and moderate exercise may be important in the pathogenesis of hypertension in this group of patients.     

Effects of statins on renal sodium and water handling: acute and short-term effects of atorvastatin on renal haemodynamics, tubular function, vasoactive hormones, blood pressure and pulse rate in healthy, normocholesterolemic humans.

BACKGROUND: Statins have a beneficial effect on cardiovascular morbidity and mortality due to a reduction in plasma cholesterol. However, statins seem to have effects beyond the lowering of plasma cholesterol. We hypothesize that these effects are caused by an effect on renal function. METHODS: We measured the effects of atorvastatin (AS) on renal function in two randomized, placebo-controlled, double-blinded and crossover studies in healthy man. In an acute trial (Study 1), 19 subjects received either 80 mg AS as a single dose or placebo. In a short-term trial (Study 2), 20 subjects received either 80 mg AS or placebo daily for 4 weeks. In both studies glomerular filtration rate (GFR), renal plasma flow (RPF), plasma concentrations of angiotensin II (Ang II), renin (PRC), atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), aldosterone (Aldo), vasopressin (AVP) and blood pressure (BP) were determined. RESULTS: In Study 1 AS decreased fractional excretion of sodium (FE(Na)) significantly (P = 0.035), but very modestly, and reduced diastolic BP (P = 0.024). Apart from this, we found no significant differences in GFR, RPF, tubular function and vasoactive hormones in either Study 1 or 2. CONCLUSIONS: An acute dose of AS decreased FE(Na) and DBP in healthy humans. The reduction in fractional urinary sodium excretion was very modest and transitory, and most likely secondary to the fall in diastolic blood pressure (DBP). However, renal haemodynamics, tubular function, vasoactive hormones and blood pressure were unchanged during short-term statin treatment in healthy man.     

Effect of felodipine on renal haemodynamics and tubular sodium handling in cyclosporin-treated renal transplant recipients.

The effect of a single oral dose of 10 mg of the calcium antagonist felodipine or placebo was investigated in 10 cyclosporin-treated renal transplant recipients before, during, and after an acute intravenous infusion of cyclosporin in a randomised, single-blind cross-over study. Renal plasma flow (RPF), glomerular filtration rate (GFR), renal tubular sodium and water handling as judged by the lithium clearance technique, and plasma concentrations of angiotensin II (AngII), aldosterone (Aldo), atrial natriuretic factor (ANF), and arginine vasopressin (AVP) were measured. Both RPF and GFR increased after felodipine (mean increase: RPF, 38.7%; GFR, 16.2%; P less than 0.01 for both) in spite of a significant decrease in both systolic and diastolic blood pressure (mean decrease 10.6% and 16.0% respectively, P less than 0.02 for both). Estimated by the lithium clearance technique felodipine induced a decrease in fractional reabsorption in the proximal tubules (mean 72.0% vs 63.0%, P less than 0.01), an increase in proximal output of fluid (mean 11.0 ml/min vs 16.0 ml/min, P less than 0.01), and a decrease in distal fractional reabsorption of sodium (mean 90.5% vs 83.9%, P less than 0.05) resulting in a significant natriuresis and diuresis. Ang II, Aldo, ANF, or AVP did not change. Intravenous infusion of cyclosporin per se did not influence any of the parameters. It is concluded that a single dose of felodipine in cyclosporin treated renal transplant recipients has beneficial effects on blood pressure, renal haemodynamics, and renal tubular sodium and water handling, which seems to compensate for some of the adverse effects of cyclosporin. It is suggested that these effects result from a direct vasodilatation and an effect on proximal tubular function.     

Hypertensive dysregulation and its modification by calcium channel blockade in nonoliguric renal failure

To investigate the pathogenetic constellation and its modification by calcium channel blockade in hypertension associated with chronic nonoliguric renal failure, blood pressure (BP), various pressor factors or correlates, cardiovascular responsiveness, and plasma atrial natriuretic peptide (ANP) were assessed in 15 hypertensive patients (serum creatinine 160-715 mumol/l) before and after 6 weeks of intervention with the agent nitrendipine. On placebo, these patients had a lower plasma angiotensin II (AngII) clearance and higher values of supine plasma AngII, aldosterone, norepinephrine (NE), and heart rate than healthy humans. Acute responses of BP to AngII and of heart rate to isoproterenol were blunted in the patients (p less than 0.05-0.001). Plasma ANP was elevated, correlated positively with systolic BP, and rose in response to NE pressor infusion (p less than 0.05-0.001). Exchangeable sodium and blood volume did not differ significantly from normal values. Nitrendipine reduced the cardiovascular responses to AngII, NE, and isoproterenol and lowered supine BP from 173/102 +/- 5/2 to 146/81 +/- 3/3 mm Hg and upright BP from 170/105 +/- 5/2 to 145/86 +/- 4/3 mm Hg (p less than 0.05-0.001); except for slightly increased plasma AngII, the levels of other endocrine variables, exchangeable sodium, blood volume, and creatinine clearance were not significantly modified. Conclusions: Hypertension accompanying chronic nonoliguric renal impairment seems to be strongly AngII and probably also NE dependent. Circulating ANP levels are high in this setting. Calcium channel blockade with nitrendipine effectively reduces cardiovascular AngII and NE dependence and BP.     

Body sodium-blood volume state, aldosterone, and cardiovascular responsiveness after calcium entry blockade with nifedipine

Exchangeable sodium, blood volume, plasma norepinephrine (NE), epinephrine, renin and aldosterone levels, and pressor responses to infused NE or angiotensin II (AII) were assessed in ten patients with essential hypertension on placebo, following 6 to 8 weeks of calcium-antagonist nifedipine (NIF), 3 X 10 to 20 mg/day, and after 6 to 8 weeks on NIF combined with the diuretic chlorthalidone (CHLOR), 25 to 50 mg/day. Pressor effects of infused calcium also were evaluated on placebo and NIF. Supine blood pressure was decreased from 151/97 +/- 5/2 (SEM) to 132/88 +/- 6/2 mm Hg after NIF alone (P less than 0.05) and to 124/83 +/- 7/3 mm Hg after NIF + CHLOR (P less than 0.01). Body wt was increased from 72.7 to 73.9 kg on NIF alone (P less than 0.05), but decreased to 72.1 (P less than 0.05 compared with placebo) after adding CHLOR. Exchangeable sodium also rose from 2642 +/- 237 to 3360 +/- 266 mmoles on NIF (+ 27%; P less than 0.01) and returned to control values (2638 +/- 248 mmoles) after addition of CHLOR. Plasma volume was only slightly modified on NIF (from 2621 +/- 193 to 2751 +/- 160 ml; + 5%), but was reduced to 2232 +/- 231 ml on NIF + CHLOR (P less than 0.05). Responses of circulating aldosterone to AII were similarly diminished (P less than 0.01) during both conditions. Heart rate, supine and upright plasma renin, aldosterone and catecholamine levels, and pressor responses to NE, AII, or calcium were not consistently changed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Vasoactive hormones in uraemic patients with chronic hypotension

Background. We evaluated the possible role of an imbalance between vasoconstrictor and vasodilator hormones in the pathophysiology of chronic hypotension in uraemia. Methods. Fourteen hypotensive haemodialysed patients, 14 normotensive haemodialysed patients, and 17 control subjects were included in this study. Plasma renin activity (PRA) and plasma levels of catecholamines, angiotensin II (AII), atrial natriuretic peptide (ANP), and arginine vasopressin (AVP) were measured. Results. The mean time on haemodialysis (HD) was longer in hypotensive patients than in normotensive patients (P <0.01). Catecholamine levels were higher in the whole group of HD patients than in controls (P <0.01). Catecholamine levels were higher in hypotensive patients than in normotensive patients, but the differences reached significance only for adrenaline (P <0.05). PRA and plasma AII levels were higher in hypotensive patients than in the other two groups (P <0.05), while no differences were observed between normotensive patients and controls. Plasma ANP and AVP levels were higher in HD patients than in controls (P <0.01), but there were no differences between hypotensive and normotensive patients. In HD patients, mean blood pressure inversely correlated with PRA (r=-0.9, P <0.01) and plasma AII levels (r=-0.80, P <0.01). Conclusion. Our results indicate that in HD patients with chronic hypotension there is an activation of the sympathetic and the renin-angiotensin systems. This activation is probably secondary in an attempt to compensate the vascular resistance to pressor stimuli reported in these patients.     

Hypotension in end-stage renal disease: effect of postural change, exercise and angiotensin II infusion on blood pressure and plasma concentrations of angiotensin II, aldosterone and arginine vasopressin in hypotensive patients with chronic renal failure treated by dialysis

In 16 dialysis patients, 8 hypotensive and 8 normotensive, and 8 control subjects, blood volumes were studied and angiotensin II (AII), aldosterone (Aldo) and arginine vasopressin (AVP) were measured in the supine position, after standing upright for 5 min and after a standard exercise test. In 8 hypotensive and 7 normotensive dialysis patients and in 7 control subjects, the pressor response to AII infusion was determined. Baseline values for AII, Aldo and AVP were the same in the different groups but with a much wider range in uremic patients. After standing for 5 min. both hypotensive and normotensive dialysis patients were able to maintain blood pressure without a significantly greater increase in heart rate than was seen in controls. Contrary to controls, however, all non-nephrectomized dialysis patients responded with an increase in AII and Aldo after standing for 5 min. In controls, exercise induced a clearcut increase in AII, Aldo and AVP, while no such changes were detectable in either hypotensive or normotensive dialysis patients. No significant differences in blood volumes were detectable between the groups. The pressor response to AII infusion was decreased in both normotensive and hypotensive dialysis patients compared with controls. It can be concluded that circulatory adjustment is abnormal in both hypotensive and normotensive dialysis patients as indicated by extremely high baseline levels of AII in some patients, abnormal response of the renin-angiotensin-aldosterone system and AVP to postural change and exercise and a decreased pressor response to AII infusion. However, neither these abnormalities nor changes in blood volumes can directly account for the chronic hypotension seen in some dialysis patients.     

Increased Plasma Levels of Atrial Natriuretic Peptide in Patients with Chronic Renal Failure: Effect of Noradrenaline Infusion

Basal plasma atrial natriuretic peptide (ANP) and blood pressurewere measured in 11 patients with chronic renal failure beforerequirement of dialysis, 13 patients on chronic dialysis, and28 control subjects (Study 1). Changes in ANP during noradrenalineinfusion were determined in eight patients with chronic renalfailure before dialysis, 12 patients on chronic dialysis, and17 control subjects (Study 2). ANP was also measured in 14 healthycontrol subjects during angiotensin II infusion (Study 3). Study1 showed a significantly greater ANP in patients before thestage of dialysis (median 23 pg/ml) and in dialysis patients(34 pg/ml) than in control subjects (19 pg/ml) p 0.01 for both.In Study 2, noradrenaline induced an increase in ANP in thenon-dialysed patients (P<0.05) and in the control subjects(P<0.01), but not in the dialysis patients. According toStudy 3, ANP was unchanged during angiotensin II infusion. Bloodpressure was increased in all groups during noradrenaline andangiotensin II infusions. It can be concluded that ANP is increasedboth in patients with chronic renal failure before requirementof dialysis and in patients on maintenance dialysis. It is suggestedthat noradrenaline stimulates ANP release.     

Assessment of dry body-weight in haemodialysis patients by the biochemical marker cGMP

We investigated whether cGMP might be a suitable marker of ideal weight in chronic haemodialysis patients. In 20 patients on chronic haemodialysis (10 males, 10 females, mean age 55.5 +/- 7.4 years; mean interdialytic weight gain 2.4 +/- 1.1 kg) we determined plasma ANP and cGMP values before and after several haemodialysis treatments. ANP and cGMP before haemodialysis were markedly elevated (ANP 255 +/- 190 pg/ml; cGMP 28.6 +/- 16.2 pmol/ml). A significant decrease was found after haemodialysis (ANP 169 +/- 88 pg/ml; cGMP 13.5 +/- 7.4 pmol/ml). These values were still well above normal. There was a significant positive correlation between excessive body-weight delta P (difference between actual weight and estimated ideal weight), indicating fluid overload and ANP before (r = 0.57; P less than 0.001) and after haemodialysis (r = 0.47; P less than 0.001) as well as cGMP before (r = 0.42; P less than 0.01) and after haemodialysis (r = 0.85; P less than 0.0001). With cGMP and delta P after haemodialysis, the correlation appeared to be close enough for clinical application. All patients with a cGMP value of 18 pmol/ml or more after haemodialysis had an excessive body-weight of at least 0.5 kg. We conclude from these data that the plasma cGMP value determined immediately after haemodialysis is a sensitive marker for hyperhydration in patients with end-stage renal disease.     

Effects of Cardiopulmonary Bypass and Prostacyclin on Plasma Catecholamines, Angiotensin II and Arginine-Vasopressin

Infusion of prostacyclin during cardiopulmonary bypass (CPB) reduces platelet activation, diminishes postoperative blood loss and decreases arterial blood pressure. In spite of continuous prostacyclin infusion, there is a delayed gradual rise in arterial pressure and resistance from low initial levels. We measured epinephrine (E), norepinephrine (NE), serotonin (5-HT), angiotensin II (ATII) and arginine-vasopressin (AVP) in plasma and carried out hemodynamic studies in 19 patients operated for coronary vascular disease. Eight patients served as a control group and were subjected to routine CPB. Eleven patients received prostacyclin 50 ng/kg/min during CPB. E and NE increased four- to sixfold during CPB from about 0.5 ng/ml (P less than 0.001). There was no difference between the groups. During CPB AVP increased sixfold from about 20 pg/ml in both groups (P less than 0.001), decreased early after CPB and increased again to high levels 3 h after CPB. The combined action of E, NE and AVP is of likely importance for the rise in systemic vascular resistance and/or need of vasodilation during CPB in the control group. ATII did not increase in the control group, but increased fourfold to about 20 pg/ml (P less than 0.01) during CPB in the prostacyclin group. The addition of AT II to E, NE and AVP seems responsible for the gradual return of arterial pressure and resistance during prostacyclin infusion. Postoperative hypertension and/or need of vasodilation 3 h after CPB was associated with high AVP levels in both groups. Hypotension caused by prostacyclin infusion did not increase E, NE or AVP above levels produced by CPB and moderate hypotension alone.     

Elevations in antidiuretic hormone and aldosterone as possible causes of fluid retention in the Maze procedure

BACKGROUND: Reduced levels of atrial natriuretic peptide (ANP) has been suggested as a cause of fluid retention after combined Maze and valvular surgery. This study aimed to assess hormonal activation in the perioperative setting of isolated Maze procedures. METHODS: Changes in ANP, brain natriuretic peptide (BNP), antidiuretic hormone (ADH), aldosterone, and angiotensin II were measured in 16 patients (mean age 53+/-9 years) without concomitant heart disease undergoing the Maze (III) procedure. Ten matched patients (mean age 56+/-9 years) undergoing multivessel coronary artery bypass grafting served as controls. Measurements with hemodynamic correlates were obtained at baseline and after ventricular pacing (100 stimulations/minute), directly preoperatively, postoperatively and the first postoperative day. Weight gain and diuretic requirements were recorded. RESULTS: The major differences in hormonal response were significantly higher plasma levels of ADH (Maze preoperative 1.1+/-0.4, postoperative 24.9+/-16.7 pmol/L; controls preoperative 1.1+/-0.1, postoperative 3.7+/-3.5 pmol/L) and aldosterone (Maze preoperative 106+/-94, postoperative 678+/-343 pmol/L; controls preoperative 124+/-79, postoperative 171+/-93 pmol/L) in the Maze group on the first postoperative day (p < 0.001). Preoperative baseline plasma levels of ANP and pulmonary capillary wedge pressures (PCWP) were higher in the Maze group but this difference was abolished by pacing, and postoperatively, ANP levels changed in parallel to the PCWP in both groups. Diuretic requirements were significantly higher in the Maze group. CONCLUSIONS: Substantial increases in ADH and aldosterone were observed after the Maze procedure, indicating these hormones as important determinants in postoperative fluid retention. The role for ANP in this setting may be a less prominent than previously reported.     

Water immersion-induced alterations of plasma atrial natriuretic peptide level and its relationship to the renin-angiotensin-aldosterone system and vasopressin secretion in acute and chronic renal failure

Water immersion (WI)-induced alterations of circulating plasma volume (PV), plasma renin activity (PRA), plasma levels of aldosterone (Ald), vasopressin (AVP) and atrial natriuretic peptide (ANP) were examined in 12 patients with noninflammatory acute renal failure (ARF) at the anuric/oliguric phase, in 20 hemodialyzed patients with chronic renal failure and in 15 healthy subjects. Patients with acute and chronic renal failure showed significantly elevated basal ANP concentrations (138.67 +/- 12.88 and 295.8 +/- 21.87 pg/ml, respectively) as compared with normals (74.54 +/- 4.1 pg/ml) and significantly elevated PRA (20.85 +/- 3.24 and 6.60 +/- 0.94 ng/ml/h, respectively versus 2.33 +/- 0.31 ng/ml/h), plasma levels of Ald (16.11 +/- 1.26 and 18.11 +/- 1.58 ng/dl, respectively versus 12.71 +/- 1.03 ng/dl) and AVP (6.95 +/- 0.62 and 6.08 +/- 0.54 pg/ml, respectively versus 2.68 +/- 0.48 pg/ml). After 2 hrs of WI a significant decline of PRA, Ald and AVP but an increase of ANP was noted in all examined groups. The absolute WI-induced increase in plasma ANP was significantly less marked in uremic patients than in normals. The endocrine profile of patients with ARF differed only quantitatively from that of patients with CRF both under basal and WI conditions. WI was followed by a significant increase of PV which was significantly more marked in patients with ARF (+ 16.42 +/- 1.73%) than in CRF (10.57 +/- 0.37%) and in normals (+11.3 +/- 1.6%). Only in healthy subjects a significant correlation was found between WI-induced changes of PV and ANP, PRA and Ald, and between PRA and AVP.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma atrial natriuretic peptide and its relation to the renin-angiotensin-aldosterone system in patients with chronic renal failure.

To determine the relationship between plasma immunoreactive atrial natriuretic peptide (i-ANP) and renin-angiotensin-aldosterone system (RAAS), plasma i-ANP, plasma renin activity (PRA) and plasma aldosterone (PA) were assayed in 29 patients (19 hypertensive and 10 normotensive) with chronic renal failure (CRF), and in 10 healthy subjects. Hypertensive patients had higher i-ANP values than normotensive patients and controls (P less than 0.05 and P less than 0.01 respectively). There was no significant correlation between plasma i-ANP and creatinine concentrations in hypertensive patients, whereas this correlation was statistically significant in normotensive patients (r = 0.70, P less than 0.01). Other positive correlations were between plasma i-ANP and systolic blood pressure in hypertensive patients (r = 0.69, P less than 0.01) and between plasma ANP and mean arterial pressure in normotensive patients (r = 0.63, P less than 0.01). There was significant negative correlation between plasma ANP and fractional sodium excretion (FENa) in hypertensive patients (r = -0.47, P less than 0.05), though there was significant positive correlation in normotensive patients (r = 0.80, P less than 0.01). Hypertensive patients, with the exception of one anuric patient and another with atrial fibrillation, had a significant negative correlation between FENa and systolic arterial blood pressure (r = 0.64, P less than 0.01). The patient group had increased PRA and PA values (P less than 0.01 and P less than 0.001 respectively) and showed positive correlation with mean arterial pressure (MAP) (r = 0.71, P less than 0.001 and r = 0.58, P less than 0.01 respectively). These results show that increased concentrations of immunoreactive ANP circulate in CRF together with activated RAAS. We demonstrate that elevated ANP cannot affect blood pressure and natriuresis in hypertensive patients with CRF, whose RAAS is activated.     

The neurohumoral response to burn injury in patients resuscitated with hypertonic saline

Fourteen adult patients (mean age, 35 yrs) with 20-60% total body surface area (TBSA) burns (mean, 35%) were resuscitated using hypertonic sodium lactate (HSL: sodium = 250 mEq/L). Plasma concentrations of atrial natriuretic peptide (ANP), arginine vasopressin (AVP), angiotensin II (A-II), epinephrine (E) and norepinephrine (NE) were measured on admission and for 7 days following burn injury. Serum sodium concentrations and osmolalities were lowest on admission, and were persistently elevated following HSL resuscitation. Plasma AVP levels were highest on admission and correlated with the size of the burn injury. Between days 4 and 5 plasma ANP levels rose while plasma AVP levels returned to normal. Plasma concentrations of AVP and ANP did not correlate with serum osmolality or serum sodium concentrations on admission or after HSL resuscitation. Plasma levels of A-II, NE and E were elevated throughout the 7-day period and were unrelated to the size of the burn.