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Statins improve cardiovascular survival in both nondiabetic and diabetic patients, but diabetic patients benefit more, in both primary and secondary prevention. Statins seem to have multiple effects beyond cholesterol lowering, that is, pleiotropic effects that may include changes in renal function. This study tests the hypothesis that acute treatment with atorvastatin may change glomerular filtration rate, tubular function, vasoactive hormones, blood pressure, and pulse rate in patients with type 2 diabetes. In an acute, randomized, placebo-controlled, double-blinded, crossover trial, the effects of atorvastatin on renal function, vasoactive hormones, blood pressure, and pulse rate are measured in 21 patients with type 2 diabetes. Patients are randomized to either 2 doses of atorvastatin 80 mg or placebo before 2 different study days. Treatment with atorvastatin induces a significant reduction in fractional sodium excretion compared with placebo, and sodium clearance tends to be reduced. No significant differences in glomerular filtration rate, albumin/creatinine ratio, vasoactive hormones, and blood pressure by acute treatment with atorvastatin are found in diabetic patients. Acute treatment with atorvastatin reduces renal fractional sodium excretion in patients with type 2 diabetes. No changes are measured in glomerular filtration rate, albumin/creatinine ratio, vasoactive hormones, and blood pressure.

Objective: Improved cardiovascular survival during statin treatment might be due to effects in addition to cholesterol lowering. We hypothesize that sodium intake affects renal function and vasoactive hormones in atorvastatin-treated healthy subjects., Methods: In a randomized, placebo-controlled, double-blind, crossover study we measured the effect of a moderate change in sodium intake on glomerular filtration rate (GFR), blood pressure (BP), renal tubular function, plasma concentrations of vasoactive hormones and urinary excretion of aquaporin-2 (u-AQP2) in 22 healthy subjects. The subjects were randomized to standardized fluid intake and diet corresponding to the need for calories in the 4 days before each of the 2 examination days. In one of the periods they were randomized to receive sodium chloride tablets (2 g) thrice daily for 4 days. Two doses of atorvastatin (80 mg) were given; one at 2200 h the evening before the study day, the other at 0830 h in the morning., Results: 24-h urinary sodium excretion increased by 23%. GFR and BP were unchanged. Sodium clearance, fractional excretion of sodium and u-AQP2 increased, whereas free water clearance decreased during high sodium intake. PRC and aldosterone were suppressed during the high sodium diet., Conclusions: A change in dietary sodium intake of approximately 100 mmol daily does not change GFR and BP in atorvastatin-treated healthy men. The lack of change in BP might reflect that the subjects studied were not sodium sensitive, or that atorvastatin treatment modified sodium sensitivity.

Objective: The mechanisms involved in the development and maintenance of hypertension in obstructive sleep apnoea (OSA) are not clear. We hypothesized that OSA patients have an abnormal renal handling of sodium and water during the night., Material and Methods: We studied 29 OSA patients and 19 healthy controls at night with serial determinations of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), arginine vasopressin (AVP), aldosterone (Aldo), fractional urinary excretion of sodium (FE(Na)), free water clearance (C(H2O)), urinary excretion of aquaporin 2 (u-AQP2), systolic blood pressure (SBP), diastolic blood pressure (DBP) and oxygen saturation., Results: OSA patients had a higher FE(Na) (0.6 (0.4-1.0) versus 0.4 (0.3-0.6) %; p = 0.017), SBP (129 (114-145) versus 114 (106-122) mmHg; p = 0.001) and DBP (81 (72-87) versus 71 (65-74) mmHg; p<0.001) than healthy controls at night. In hypertensive OSA patients, the FE(Na) correlated significantly with the change in nocturnal DBP (r (2) = 0.411; p = 0.010). Mean level of AVP during the night was higher in OSA patients compared with healthy controls (1.1 (0.8-1.4) versus 0.8 (0.6-1.1) pmol/L; p = 0.033) and correlated with SBP. ANP, BNP, Aldo, C(H2O) and u-AQP2 were the same in OSA and controls., Conclusions: We conclude that the higher fractional excretion of sodium in OSA is most likely attributable to pressure natriuresis. The correlation between mean AVP and blood pressure suggests that AVP may be part of the pathogenetic mechanism underlying hypertension in these patients.

Background: Greenlanders have a lower rate of cardiovascular mortality and morbidity than Danes, possibly due to lower blood pressure. However, 24-h blood pressure has never been measured in Greenlanders. The aim of this study was to compare the 24-h blood pressure of Greenlanders and Danes, and to analyse the influence of Arctic food and lifestyle on blood pressure., Methods: Four groups of healthy subjects were recruited for the study. Group I: Danes in Denmark consuming European food; group II: Greenlanders in Denmark consuming European food; group III: Greenlanders in Greenland consuming mainly European food; and group IV: Greenlanders in Greenland consuming mainly traditional Greenlandic food. All subjects underwent a physical examination, laboratory screening of blood and urine samples, and completed a questionnaire on diet, physical activity, smoking status, intake of alcohol, liquorices, vitamins and minerals. Twenty-four-hour blood pressure was measured., Results: It was found that 24-h diastolic blood pressure was lower in Greenlanders than in Danes for the whole 24-h period and during both day and night-time, whereas systolic blood pressure was the same (mean 24-h blood pressure with 95% CI: Danes 123/75 mmHg (120/73-127/77), Greenlanders 122/ 69 (119/68-124/70)). Among Greenlanders, blood pressure increased with age and male gender, and systolic blood pressure increased with body mass index (BMI). No association with diet was found. The difference between the two populations persisted after controlling for age, gender, BMI, outdoor temperature, and lifestyle factors., Conclusion: Greenlanders have a lower 24-h diastolic blood pressure than Danes, and it is suggested that genetic factors are mainly responsible for the lower blood pressure level among Greenlanders.

Background: Due to their vasodilatory effect, calcium antagonist may have a renoprotective against cyclosporin (CsA)-induced nephrotoxicity and rise in blood pressure (BP) seen in renal transplantation., Methods: In order to evaluate the effect of the calcium antagonist felodipine on renal function and BP during cyclosporin treatment, 79 CsA-treated renal transplant recipients were investigated during the first 3 months after transplantation in a randomized, double-blind, placebo-controlled study with two parallel groups. Felodipine (ER tablets, 10 mg) or placebo was given prior to transplantation and each day during the study period. The patients were assessed twice, i.e. at 4-6 weeks and at 10-12 weeks after transplantation. Renal plasma flow (RPF) and glomerular filtration rate (GFR) were measured by constant infusion technique. Tubular function was estimated from clearance of lithium., Results: At 6 weeks after transplantation, felodipine caused a significantly higher RPF [felodipine: 219 +/- 70 ml/min; placebo: 182+/-56 ml/min (mean+/-1 SD); P=0.03]. No differences were found in GFR, filtration fraction (FF), tubular sodium handling, or sodium excretion. Felodipine lowered BP significantly. At 12 weeks after transplantation, felodipine caused a significantly higher GFR (felodipine: 49+/-18 ml/min; placebo: 40+/-16 ml/min; P=0.05) and RPF (felodipine: 225+/-77 ml/min; placebo: 175+/-48 ml/min; P<0.01). No difference was found in FF. Felodipine lowered BP significantly. No differences were found with regard to duration of primary anuria, hospitalization time, number of rejection episodes, plasma creatinine day 7 post-transplant, or treatment doses of CsA., Conclusions: It is concluded that in renal transplant recipients treated with CsA, felodipine significantly increased both GFR and RPF 3 months after transplantation when compared with placebo, despite a concomitant lowering of BP. A possible antagonizing affect of felodipine against CsA-induced nephrotoxicity in these patients is suggested.

The purpose of this study was to assess the blood pressure profile and to measure vasoactive hormones in patients with essential hypertension (n=61), secondary hypertension (n=32) and chronic renal failure (n=32) matched with healthy control subjects (n=35), and to study the relationship between circadian changes in blood pressure and baseline levels of vasoactive hormones and renal function. Non-invasive, automatic blood pressure measurement was performed for 24 or 48 h. Venous plasma concentrations of renin, angiotensin II, aldosterone, arginine vasopressin, atrial natriuretic peptide and endothelin were measured. The mean 24-h blood pressure was higher in all groups of hypertensive patients than in control subjects. The nocturnal blood pressure fall was preserved in essential hypertension, in contrast to secondary hypertension in which it was attenuated. In the patients with chronic renal failure the 24-h mean blood pressure was the same as in the controls. Night-time blood pressure was higher among the chronic renal failure patients than in the control group, and the nightly blood pressure fall in both diastolic and systolic blood pressure was reduced. Plasma concentrations of renin activity, arginine vasopressin, atrial natriuretic peptide, aldosterone and endothelin were significantly increased in secondary hypertension and chronic renal failure, compared to essential hypertension and control subjects. Plasma angiotensin II was increased in chronic renal failure compared to essential hypertension and controls. Estimated creatinine clearance and nightly blood pressure dips were inversely correlated in essential and secondary hypertension, i.e. with a decreasing renal function both systolic and diastolic nightly blood pressure dips were gradually attenuated. In the whole group of patients the nightly systolic and diastolic blood pressure dips were negatively correlated to basal plasma renin activity, plasma aldosterone and atrial natriuretic peptide levels, i.e. the higher the basal plasma hormone level the lower the blood pressure dip. In conclusion, patients with essential hypertension have elevated but normally configured 24-h blood pressure profiles, and patients with different kinds of secondary hypertension have elevated 24-h blood pressure profiles and attenuated nightly systolic and diastolic blood pressure falls. The more the renal function is reduced and the more the plasma levels of renin and aldosterone are increased, the more the nocturnal fall in blood pressure is reduced. It is suggested that the attenuated or absent decrease in nocturnal blood pressure in secondary renal hypertension is caused by an abnormally increased secretion of vasoactive hormones and/or by so far unknown factors released from the diseased kidney.

The aim of this study was to assess the blood pressure profile and vasoactive hormones in valvular aortic disease. Thirteen aortic stenosis and/or aortic regurgitation patients were matched with 13 control subjects. Ambulatory blood pressure monitoring was performed for 24 h. Arterial and venous plasma concentrations of renin, angiotensin II, aldosterone, arginine vasopressin, atrial natriuretic peptide, immunoreactive endothelin and cyclic-GMP were measured. The mean 24-h blood pressure was higher in the patient group (94.9 mmHg) compared with control subjects (88.2 mmHg) (p < 0.0001), despite no differences in daytime blood pressures. The nocturnal blood pressure fall was attenuated in the patients (systolic/diastolic blood pressure -8.5/-3.5; -20.3/-14.3 mmHg (p < 0.001/p < 0.01)); in heart rate too the nightly fall was blunted in the patients (-4.8/ -13.4/min (p < 0.0013)). PRA, Ang II, AVP, ANP, ir-ET and cGMP were significantly increased in the patients compared to the controls. Nightly systolic blood pressure fall was inversely related to arterial (r = -0.75, p < 0.003) and venous (r = -0.65, p < 0.04) plasma renin activity and arterial aldosterone (r = -0.64, p < 0.05) in valvular aortic disease patients. In conclusion, valvular aortic disease patients have attenuated falls in blood pressure and heart rate during the night. Increased activity in the renin aldosterone system may be involved in this abnormal blood pressure regulation.

Objective: To study the influence of blood pressure reduction with sodium nitroprusside on the renal glomerular and tubular actions of atrial natriuretic peptide., Design: Forty-nine healthy subjects were examined in four different groups receiving placebo, sodium nitroprusside alone, atrial natriuretic peptide alone (10 ng/kg per min), or sodium nitroprusside and atrial natriuretic peptide in combination. The infusion rate of sodium nitroprusside was gradually increased until a 10 mmHg decrease in diastolic blood pressure was obtained., Methods: Lithium clearance was used to evaluate segmental tubular reabsorption., Results: In the placebo group neither renal nor hormonal parameters were changed. Except for a fall in urinary flow, sodium nitroprusside alone had no effect on renal parameters. Urinary excretion of cyclic GMP (cGMP) was slightly increased, whereas the plasma cGMP level was not changed in response to sodium nitroprusside. The plasma aldosterone level was elevated during sodium nitroprusside infusion, although neither the plasma angiotensin II level nor the plasma atrial natriuretic peptide level were changed. Atrial natriuretic peptide alone caused an increase in filtration fraction and a decrease in renal plasma flow. Urinary sodium excretion, fractional sodium excretion, and urinary flow were increased, and distal fractional tubular sodium absorption decreased, whereas lithium clearance and proximal fractional tubular re-absorption were not changed by atrial natriuretic peptide. Atrial natriuretic peptide alone caused a decrease in plasma aldosterone and an increase in plasma and urinary cGMP levels. During blood pressure reduction with sodium nitroprusside, atrial natriuretic peptide caused no changes in the renal parameters except for an increase in filtration fraction. Thus, the increase in urinary sodium excretion (-8 versus +37 micromol/min) and the decrease in distal fractional sodium excretion (0.0 versus -2.4%) caused by atrial natriuretic peptide were attenuated. The atrial natriuretic peptide-induced changes in proximal fractional tubular reabsorption (-0.5 versus +0.6%) and cGMP were not changed by blood pressure reduction., Conclusions: Blood pressure reduction causes an attenuation of the natriuretic action of atrial natriuretic peptide in normotensive humans that is at least partly caused by attenuation of the distal tubular action of atrial natriuretic peptide. The results support the hypothesis that the action of atrial natriuretic peptide on distal tubular sodium reabsorption is pressure-dependent in humans.

The effect of prednisolone, given as a 4-day oral treatment, on 24-h ambulatory blood pressure rhythm, vasoactive hormones and correlation between blood pressure and vasoactive hormones were studied in 11 healthy men. Blood pressure was monitored at intervals of 15 min during the day and of 30 min during the night. Plasma concentrations of angiotensin II, aldosterone, atrial natriuretic peptide (ANP) and arginine vasopressin and serum concentration of insulin were measured in the morning during basal conditions. The 24-h systolic, diastolic and mean blood pressures were significantly higher after prednisolone treatment. Waking blood pressure was not significantly changed, but sleeping systolic and mean blood pressures were significantly elevated after treatment. The nocturnal systolic blood pressure fall was less pronounced after treatment (before 22%, and after 16%, p<0.01), whereas the nocturnal, mean and diastolic dips were preserved. ANP was significantly increased by prednisolone treatment, from 10.1 to 14.6 pmol l-1, p<0.005. The changes in concentration of ANP were significantly correlated to the changes in 24-h diastolic blood pressure (r = -0.63, p<0.05), 24-h mean blood pressure (r = -0.68, p<0.05), waking diastolic blood pressure (r = 0.83, p<0.01) and waking mean blood pressure (r = -0.67, p<0.01). We found that short-term prednisolone treatment elevated the overall 24-h blood pressure, reduced systolic blood pressure fall during sleep, and increased plasma concentration of ANP, and that the increase in ANP was inversely correlated to the increase in blood pressure. We suggest that the increase in ANP is a secondary and compensatory phenomenon which at least to some extent counteracts the hypertensive and sodium retaining effect of prednisolone.

Ambulatory blood pressure was measured in 23 microalbuminuric Type 1 diabetic patients without hypertension. Nine patients had a reduction in mean arterial blood (MAP) pressure at night < 10% of their day-time value (non-dippers). The following parameters were measured: glomerular filtration rate (GFR), overnight urinary excretion of albumin (UAE), sodium and potassium, left ventricular dimensions, extracellular volume (ECV), plasma aldosterone, and arginine vasopressin (AVP). Night-time MAP was 11 mmHg lower in patients designated as dippers than in non-dippers. Day-time MAP was similar in dippers (98 +/- 5 mmHg) and non-dippers (99 +/- 8 mmHg, NS). No statistical significant difference was found for UAE in dippers (geometric mean, x/- tolerance factor, microgram min-1) (72 x/- 2.1) vs non-dippers (63 x/- 2.1), for left ventricular mass index (63 +/- 12 vs 59 +/- 10 g m-2), or for GFR (134 +/- 19 vs 148 +/- 22 ml min-1). Aldosterone and AVP were lower in non-dippers (p < 0.05) and a negative correlation in all patients was noticed between ECV and aldosterone (rho = -0.50, p < 0.05). Sodium and potassium excretion and ECV were indistinguishable between the groups. We conclude (1) that impaired reduction of night blood pressure does not seem to be associated with more signs of renal or cardiac lesions and (2) that the lower aldosterone and AVP in non-dippers may counteract volume expansion.

Background: In some vascular beds calcium-channel-blocking agents have been shown to possess some antagonism to endothelin-1 (ET-1)-induced vasoconstriction. This issue has not been well investigated in humans, however., Methods: The study had a double-blind cross-over design. In 12 healthy human volunteers we investigated the effect of pretreatment with either isradipine 10 mg daily for 1 week or placebo on changes in (i) systemic and renal haemodynamics and (ii) renal handling of sodium and water induced by intravenous infusion of ET-1 at a rate of 1 pmol/min/kg for 60 min., Results: Infusion of ET-1 affected systemic haemodynamics. The increase in diastolic blood pressure was similar after pretreatment with placebo (+6.8%) or isradipine (+5.3%). The changes in renal haemodynamics in response to ET-1 infusion were also familiar, e.g. renal plasma flow (-32.1% versus -31.2%), glomerular filtration rate (-8.8% versus -10.9%) and renal vascular resistance (+55.1% versus +52.7%). Likewise the changes in renal handling of sodium and water in response to ET-1 infusion were unaffected by pretreatment with placebo or isradipine, e.g. sodium excretion (-44.6% versus -40.8%), urine flow rate (-49.8% versus -38.9%) and clearance of lithium (-32.0% versus -29.1%)., Conclusions: Intravenous infusion of ET-1 in healthy humans discretely increases diastolic blood pressure and profoundly decreases renal haemodynamics and excretion of sodium and water. Pretreatment with the calcium-channel blocking agent isradipine for 1 week in a clinically relevant dose does not interfere with the action of ET-1.

Objective: To examine whether the effect of atrial natriuretic peptide (ANP) on renal glomerular and tubular segmental handling of sodium in patients with essential hypertension is pressure dependent., Design: Part 1. The renal effects of a low-dose continuous infusion (10 ng kg-1 min-1) with ANP for 1 h were compared in 10 untreated essential hypertensives (EH) and 13 normotensive control subjects (CS). Part 2. The hypertensives were studied on another day with ANP infusion during preceding acute BP reduction with sodium nitroprusside infusion (NP). The results were compared with those obtained during infusion with ANP+placebo (Part 1)., Methods: Lithium clearance was used to estimate the proximal tubular reabsorption of sodium., Results: Part 1. Atrial natriuretic peptide caused an exaggerated increase in urinary sodium excretion (+102 vs. +38%: P < 0.05), fractional excretion of sodium (+80 vs. +37%: P < 0.05), and urinary output (+56 vs. +8.3%; P < 0.05) in EH compared with CS. Glomerular filtration rate and filtration fraction increased to the same degree in both groups. Absolute lithium clearance (CLi) increased and FELi tended to increase (P = 0.061) in EH, but these were unchanged in CS. The increase in plasma cyclic guanosine 5'-phosphate (cGMP) and urinary excretion of cGMP and the decrease in plasma aldosterone during ANP infusion were the same in the two groups. Part 2. During NP infusion the natriuresis caused by ANP in EH was reduced (+51 vs. +99%; P < 0.05). The relative changes in GFR, CLi, and FELi during ANP infusion were not affected by the preceding BP reduction with NP. Mean arterial pressure was reduced from 122 to 101 mmHg during NP infusion. The relative increase in sodium excretion in EH was significantly correlated to mean arterial pressure., Conclusions: Low-dose ANP infusion causes an exaggerated natriuresis in untreated essential hypertensives due to a more pronounced reduction in tubular reabsorption. After BP reduction, the natriuresis induced by ANP in essential hypertensives is decreased, probably due to a less pronounced reduction in tubular reabsorption beyond the proximal tubules. We suggest that the enhanced natriuretic response to ANP in EH in secondary in some degree to the elevated systemic pressure.

Objective: To study the effect of Captopril on ambulatory blood pressure, renal and cardiac function and extracellular volume in microalbuminuric Type 1 diabetic patients., Design: Randomized, double blind placebo controlled study of two years duration., Setting: University clinic., Patients: Twenty-two patients without hypertension., Intervention: Patients received 50 mg Captopril or placebo twice a day., Measurements: Ambulatory blood pressure, renal function, extracellular volume, and echocardiographic indices of cardiac function and dimensions were assessed annually. Clinic blood pressure and urinary albumin excretion were measured every 3 months., Results: Twenty-four hour mean arterial blood pressure was unchanged in the Captopril group (mean +/- SD) (baseline 93 +/- 4 and follow up 91 +/- 8 mmHg) and in the placebo group (96 +/- 7 and 97 +/- 10 mmHg, NS). Night/day ratio of blood pressure was unaffected. Glomerular filtration rate was unchanged and renal plasma flow increased in the Captopril (557 +/- 97 and 600 +/- 112 ml min-1) versus the placebo group (574 +/- 85 and 535 ml min-1, p = 0.05). Filtration fraction was reduced in the Captopril versus the placebo group (p < 0.05). Extracellular volume and echocardiographically derived parameters were unaffected. The relative change in day time mean arterial blood pressure in the Captopril group correlated with changes in urinary albumin excretion (Spearmans r = 0.85, p < 0.05) unlike clinic mean arterial blood pressure (r = 0.33, p = 0.35)., Conclusion: Diurnal rhythm of blood pressure was unaffected by long term administration of Captopril. Renal plasma flow was increased and filtration fraction reduced. A significant association between changes in urinary albumin excretion and blood pressure after Captopril was revealed only by the implementation of ambulatory blood pressure measurements.

In order to evaluate the role of the hyperparathyroid state for blood pressure and volume homeostasis, eight patients with primary hyperparathyroidism were studied before and after corrective surgery. Neither noradrenaline induced blood pressure changes nor basal blood pressure were affected by the operation, and the values were the same as in an age- and sex-matched control group. Noradrenaline infusion induced an increase in PTH(1-84) values before (72-86 ng l-1, medians, p < 0.02), in contrast to a decrease after (28 to 19 ng l-1, p < 0.05) operation for primary hyperparathyroidism. Basal plasma atrial natriuretic peptide was lower before than after removal of adenomata (3.2 vs. 4.8 pmol l-1, medians, p < 0.02). Cyclic 3'-5'-guanosine monophosphate was not significantly changed (4.7 vs. 5.5 nmol l-1). Aldosterone was higher before than after surgery (139 vs. 71 pmol l-1, p < 0.02), whereas angiotensin II was unaltered (20 vs. 9 pmol l-1). Arginine vasopressin was higher before than after the operation (0.9 vs. 0.7 pmol l-1, p < 0.05), but urinary excretion of prostaglandin E2 was unchanged. In conclusion primary hyperparathyroidism was not associated with changes in noradrenaline reactivity or basal blood pressure despite derangements of hormones adjusting sodium and water homeostasis. It is suggested that the hormonal changes may be secondary to a relative volume depletion.

In order to evaluate the hormonal regulation of blood pressure (BP) in uraemia 12 patients on chronic maintenance dialysis and 14 healthy controls were studied. BP and plasma concentrations of atrial natriuretic peptide (ANP), cyclic 3',5'-guanosine monophosphate (cGMP), and intact parathyroid hormone (PTH(1-84)) were determined before, during, and after a 60 min noradrenaline infusion 0.1 micrograms kg-1 body wt. min-1. Mean BP increased to the same extent in the uraemic patients (median 15 mmHg, range 6-25 mmHg) as in the controls (12 mmHg, 5-25 mmHg). ANP increased during noradrenaline infusion both in patients (7.2 to 8.3 pmol/l, medians, p < 0.01) and in controls (4.4 to 6.0 pmol/l, p < 0.01), and so did cGMP (patients: 31.6 to 35.9 nmol/l, p < 0.05; controls: 6.6 to 8.7 nmol/l, p < 0.01). PTH(1-84) was higher in the uraemic patients than in the controls, but was unchanged during noradrenaline infusion in both groups. Correlation analyses gave no evidence of a direct relation between BP and ANP, but basal PTH(1-84) was negatively correlated to basal mean BP in the patients (rho = -0.615, p < 0.05), but not in the controls. In conclusion, noradrenaline induced similar elevations of BP in dialysis patients as in healthy controls despite elevated ANP and PTH(1-84) in the patients, and ANP release was stimulated in both groups. PTH(1-84) may participate in blood pressure regulation in uraemic patients.

1. Eleven patients on chronic maintenance dialysis were investigated before and after intravenous bolus injection of atrial natriuretic peptide (2 micrograms/kg body weight). 2. Mean blood pressure was reduced to the same extent in the uraemic patients as in 11 healthy subjects, with a nadir 3 min after the atrial natriuretic peptide injection at which time mean blood pressure was reduced by 13% (median) in the uraemic patients and 11% in the healthy subjects. 3. Basal plasma atrial natriuretic peptide and guanosine 3':5'-cyclic monophosphate levels were higher in the uraemic patients than in the healthy subjects, but guanosine 3':5'-cyclic monophosphate increased markedly in both groups after atrial natriuretic peptide injection. 4. Using changes in gamma-emission from blood after previous labelling of erythrocytes with 51Cr, and changes in packed cell volume, haemoglobin and erythrocyte count, a reversible shift of fluid from the intravascular phase was demonstrated in the uraemic subjects. The blood volume was maximally reduced by 6% (median) of initial blood volume at 30 min after atrial natriuretic peptide injection. 5. Correlation analyses gave no evidence of a causal relationship between the changes in mean blood pressure and changes in blood volume, angiotensin II, aldosterone or arginine vasopressin after atrial natriuretic peptide injection. 6. It is concluded that a pharmacological dose of atrial natriuretic peptide reduces blood pressure in uraemic patients on maintenance dialysis to the same extent as in healthy subjects. The blood-pressure-reducing effect of atrial natriuretic peptide does not seem to be mediated by its diuretic effect or ability to displace fluid from plasma to the interstitial fluid compartment.

Fourteen patients with severe hypertension and renal artery stenosis were treated surgically. One patient died 4 days after surgery due to a cerebral thrombosis. The other 13 patients were followed for 18-24 months. Five were considered cured since the diastolic blood pressure (DBP) was less than or equal to 90 mm Hg without therapy. Five were improved since DBP was less than or equal to 100 mm Hg during treatment with only one or two antihypertensive agents. There were unchanged. Renal vein renin ratio (RVRR) was greater than or equal to 1.5 either before or after furosemide in all patients who were cured or improved and less than or equal to 1.5 in 2 of 3 who were unchanged. It can be concluded that surgical treatment cured or improved 77% of the patients, and that a RVRR greater than or equal to 1.5 is a good predictor of the blood pressure lowering effect of surgery.

Eleven patients with malignant arterial hypertension and malignant nephrosclerosis, verified by percutaneous renal biopsy, were examined during an observation period of 47 months (median). All patients received antihypertensive therapy. Patients were divided into three groups with regard to development of renal function during the observation period. In two patients (group I), the integrated average blood pressure (IA-BP) was 134/95 mmHg (median) and the calculated creatinine clearance (Ccr) increased from 19 to 56 ml/min (medians). In four patients (group II), IA-BP was 154/102 mmHg and Ccr remained stable-at approximately 60 ml/min. In five patients, (group III), IA-BP was 189/114 mmHg, owing to lack of patient compliance and absence from regular control, and Ccr was reduced from 26 ml/min to less than 5 ml/min. During the first 2 months of antihypertensive therapy, renal function was temporarily reduced in 7 of the 11 patients. It is concluded that effective blood pressure control in patients with malignant arterial hypertension and malignant nephrosclerosis can be accompanied by a considerable improvement, or at least a preservation of renal function.

Glomerular filtration rate (GFR) (thalamate clearance), renal plasma flow (RPF) (hippuran clearance), and urinary albumin excretion rate (AER) were measured in 10 normoalbuminuric, normotensive insulin-dependent diabetic patients and 8 normal subjects before and during acute angiotensin converting enzyme (ACE) inhibition by means of enalapril (10 mg IV). The effect of placebo versus enalapril (30 mg day-1) was also studied for 3-month treatment periods in the insulin-dependent diabetic patients. Acute ACE-inhibition caused a decline in filtration fraction (FF) from 0.259 +/- 0.011 (+/- SE) to 0.237 +/- 0.013 (2p less than 0.01) in the diabetic patients, and from 0.210 +/- 0.010 to 0.188 +/- 0.006 (2p less than 0.02) in the normal subjects. Mean arterial blood pressure was lowered from 90 +/- 1 to 84 +/- 2 mmHg (2p less than 0.01) and from 91 +/- 1 to 86 +/- 2 mmHg (2p less than 0.05). No significant change in blood glucose, AER or fractional albumin excretion (theta Alb) was seen in either group. After 3 months of enalapril treatment FF was decreased from 0.253 +/- 0.011 to 0.235 +/- 0.011 (2p less than 0.05), AER from 5.6 x/ divided by 1.7 to 4.3 x/divided by 1.6 micrograms min-1 (2p less than 0.01) and theta Alb from 1.22 +/- 0.22 x 10(-6) to 0.92 +/- 0.12 x 10(-6) (2p less than 0.02). The decline in total renal resistance was not significant (0.175 +/- 0.013 to 0.165 +/- 0.012 mmHg ml-1 min-1) and significant changes in GFR, RPF, mean arterial pressure or HbA1c were not observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Thirty patients with mild or moderate essential hypertension, and a fixed elevation of diastolic blood pressure, were randomly allocated to three groups and treated with propranolol 40 mg x 4 (Group 1), 80 mg x 4 (group 2) and 160 mg x 4 (Group 3). Blood pressure (BP), pulse rate (PR), plasma renin activity (PRA), plasma aldosterone concentration (PAC), total plasma propranolol (tPP), free plasma propranolol (fPP), and 24 h urinary propranolol excretion (UP) were determined at the end of four consecutive periods: (A) after four weeks without any treatment; (B) after two to three weeks during which the propranolol dose was gradually increased to the intended level; (C) after four weeks, and (D) after eight weeks of unchanged treatment. The maximum reduction in diastolic BP occurred after period B, and in systolic BP after Period C, for Groups 2 and 3, and for all groups together; for Group 1, however, the maximum diastolic BP reduction was first seen after period C. PR was reduced to the same level in all groups after period B. After period B, PRA an PAC fell in all groups, and remained reduced during C and D Group 1. After periods C and D, PRA and PAC in Groups 2 and 3 did not differ significantly from the levels after period A; tPP, fPP and UP were significantly correlated with the propranolol dose, and were lowest in Group 1 and highest in Group 3; UP was negatively correlated with systolic but not diastolic BP in Periods B, C and D. In contrast neither fPP nor tPP were correlated with systolic or diastolic BP. There was no significant correlation between PRA, PAC and changes in PRA or PAC on the one hand and tPP, fPP, UP, BP or changes in BP on the other. It was concluded that propranolol effectively reduced BP, but diastolic BP reduction was most rapidly obtained at 320 and 640 mg daily, that the activity of the renin -aldosterone system was initially suppressed in all group, but for unknown reasons it increased towards the control level after seven to eleven weeks of therapy with 320 and 640 mg/day, and that the reduction in systolic BP increased with higher doses of propranolol and with increasing urinary propranolol excretion.

Among 9 hypertensive recipients with kidney transplant artery stenosis (KTAS) evidence of increased activity of the renin system was present in 3. Surgical repair of KTAS in 4 recipients resulted in an increase in renal plasma flow and glomerular filtration rate associated with a decrease in exchangeable sodium and blood pressure. Peripheral plasma renin and aldosterone values were normal before and after operation in all. It is suggested that sodium retention may counterbalance increased activity of the renin system in KTAS. Preoperative determinations of plasma renin do not predict the effect of surgical repair of KTAS on hypertension.

Percutaneous transluminal renal angioplasty (PTRA) was attempted in 17 patients with a diastolic blood pressure greater than or equal to 95 mmHg in spite of treatment with two or three antihypertensive drugs in combination and unilateral or bilateral renal artery stenosis with a reduction of vessel diameter to less than 25%. PTRA resulted in a dilatation of the stenosis in 12 patients. After an observation period of at least 6 months 2 patients were cured, 7 improved and 3 unchanged. Renal vein renin ratio (RVRR) was determined in the last 9 of these patients but was unknown when PTRA was done. RVRR was higher than 1.5 in 5 patients of whom one was cured and 4 improved and less than 1.5 in 4 of whom one was improved and 3 unchanged. No persistent complications were observed after PTRA. It can be concluded that PTRA is an effective antihypertensive treatment in several patients with renovascular hypertension, and a RVRR greater than 1.5 suggests a favourable outcome with regard to blood pressure regulation.

Blood volume, extracellular volume, blood pressure and the plasma levels of angiotensin II, aldosterone, adrenaline, noradrenaline and arginine vasopressin were determined in sixteen normotensive (group 1) and thirteen hypertensive patients (group 2) with chronic glomerulonephritis and in eleven normotensive control subjects (group 3). Blood volume and extracellular volume did not differ between the groups and no significant differences were found in any of the hormones measured when comparing group 1 or group 2 with group 3. In the hypertensives but not in the normotensives or control subjects, a highly significant positive correlation was found between diastolic blood pressure and blood volume (rho = 0.75, P less than 0.01) and between diastolic blood pressure and extracellular volume (rho = 0.74, P less than 0.01). Blood volume and extracellular volume correlated (P less than 0.05) in each of the groups. In conclusion, although no expansion of either blood or extracellular volume was found in chronic glomerulonephritis, a positive volume-pressure relationship could be demonstrated in hypertensive patients suggesting a role of volume factors in the pathogenesis in early stage chronic glomerulonephritis. The study does not give support to a major role of either angiotensin II, arginine vasopressin or catecholamines in the maintenance of nonmalignant hypertension in early stage chronic glomerulonephritis.

Arginine vasopressin (AVP) and serum osmolality (Sosm) were determined in plasma before and after a 24-h period of water deprivation in 19 patients with post-renal-transplant hypertension (group I), 14 patients with normal blood pressure after renal transplantation (group II), and 16 healthy control subjects (group III). Urine was collected in four periods of 6 h each for measurement of urine volume (V), urine osmolality (Uosm) and tubular capacity for reabsorption of water (Tc water). AVP and Sosm increased significantly in all groups. The AVP levels were the same in groups I and II, but higher in group I than III both before and after water deprivation. In group II, AVP was higher than in group III only after water deprivation; V was significantly reduced in all groups. In groups I and II, V, Tc water and Uosm were the same. In group III, V was significantly lower than in groups I and II in the last three 6-h periods, and in group III, Tc water was higher in the first 6-h period than in groups I and II. There was a significant positive correlation between AVP and Sosm in all groups. In conclusion, renal water excretion cannot be reduced as rapidly and to the same degree in renal transplant recipients as in control subjects because of a decreased renal capacity for reabsorption of water. The higher AVP level in the transplant recipients may be a compensatory phenomenon for the decreased responsiveness of the renal collecting ducts in the transplanted kidneys. The sensitivity of the osmoreceptors to changes in osmotic stimuli was normal.

Casual blood pressure (BP) and ambulatory BP (mean 24-h BP) were determined in 23 untreated patients with essential hypertension and in 11 normotensive healthy control subjects. Mean 24-h BP was significantly lower than casual BP in patients with essential hypertension, but not in control subjects. This was demonstrated in the patients who did not work during the ambulatory BP monitoring and in the patients with newly recognized hypertension, whereas no differences were revealed either in the patients who went to work or had a known duration of hypertension longer than 6 months. The size of the difference between casual BP and mean 24-h BP was unaffected by antihypertensive therapy with metoprolol and also individually reproducible. An accordance between casual and ambulatory BP measurements in evaluation of the efficacy of antihypertensive treatment was found in 75% of the patients. Casual BP and mean 24-h BP were weakly correlated both before and during antihypertensive treatment. It is concluded that the higher casual BP than ambulatory BP in essential hypertension may be a specific characteristic of the disease. Both work and known duration of hypertension longer than 6 months eliminate the difference between casual ambulatory BP in essential hypertension. Ambulatory BP monitoring seems to be superior to casual BP measurements in the evaluation of antihypertensive treatment.

Objective. Obstructive sleep apnoea (OSA) is a risk factor for cardiovascular morbidity and mortality. The mechanism is unknown, but endothelial dysfunction might contribute. We tested the hypothesis that patients with OSA have abnormal nitric oxide (NO) synthesis, which results in an abnormal response in blood pressure, renal hemodynamics, renal tubular function and vasoactive hormones in response to inhibition of the NO synthesis with l-NMMA. Material and methods. A randomized, placebo-controlled, single-blinded, crossover study was done in 13 OSA patients and 14 controls. We measured changes in systolic and diastolic blood pressure (SBP and DBP), pulse rate, glomerular filtration rate, renal plasma flow, fractional excretion of sodium and lithium and plasma concentrations of vasoactive hormones after injection of l-NMMA and placebo. Results. l-NMMA induced a significant increase in SBP and DBP in both groups. The placebo-corrected increase in DBP was more pronounced in patients with OSA than in controls (9 (5-11) versus 3 (1-6) mmHg; p = 0.01). Endothelin-1 (ET-1) was significantly higher in patients compared with controls (1.1 (1.0-1.3) versus 0.8 (0.7-0.9) pg/mL; p<0.01). In controls, l-NMMA induced a small increase in ET-1, while no changes were seen in patients. The placebo-corrected change in ET-1 was lower in patients compared to controls (-01 (-0.3-0.0) versus 0.1 (0.0-0.1) pg/mL; p = 0.04). Conclusions. Patients with OSA have abnormally increased NO synthesis and an increased unresponsive level of ET-1 in plasma. This might be due to an imbalance between NO synthesis and ET-1 production. [ABSTRACT FROM AUTHOR]

Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit the enzyme cyclooxygenase and thereby block the prostaglandin (PG) synthesis in the kidneys. In animals, PG interferes with the formation of aquaporin 2 in the distal renal tubules. The purpose was to measure the effect of ibuprofen on urinary excretion of aquaporin-2 (u-AQP2), urinary output, urinary osmolality (u-osm) and plasma concentration of vasopressin (AVP) in a dose-response study using placebo and ibuprofen 600mg and 1200mg. In 12 healthy subjects, urine was collected in 6 periods between 07.00 h and 13.00 h, and blood samples were drawn at 60-min intervals. The study medication was given 10 h and 1 h before the study. U-AQP2 and AVP were determined by radioimmunoassays. U-AQP2 decreased 33% in the placebo group and increased 47% in the ibuprofen groups. There was a highly significant difference between the placebo group, on the one hand, and the ibuprofen groups, on the other. There was a small but significant increase in AVP in the placebo group and the 600 mg ibuprofen group, but not in the 1200 mg ibuprofen group. Urinary output was at maximum after 2 h, with a 394%, 1020% and 714% increase for placebo, 600 mg ibuprofen and 1200 mg ibuprofen, respectively. U-osm decreased during the experiment in all three groups. Inhibition of renal prostaglandin synthesis by ibuprofen affects the distal part of the nephron by increasing u-AQP2. This increase was not related to changes in AVP, urinary output or urinary osmolality. We suggest that the increased excretion of AQP2 can be explained by an increase in the ratio of AQP2 that is shed into the urine because the endocytic retrieval of AQP2 from the apical membrane is impaired. This could not be revealed by changes in the osmoregulatory system by the low doses of ibuprofen used in the present study. [ABSTRACT FROM AUTHOR]

Basal plasma atrial natriuretic peptide (ANP) and blood pressure were measured in 11 patients with chronic renal failure before requirement of dialysis, 13 patients on chronic dialysis, and 28 control subjects (Study 1). Changes in ANP during noradrenaline infusion were determined in eight patients with chronic renal failure before dialysis, 12 patients on chronic dialysis, and 17 control subjects (Study 2). ANP was also measured in 14 healthy control subjects during angiotensin II infusion (Study 3). Study 1 showed a significantly greater ANP in patients before the stage of dialysis (median 23 pg/ml) and in dialysis patients (34 pg/ml) than in control subjects (19 pg/ml) 0.01 for both. In Study 2, noradrenaline induced an increase in ANP in the non-dialysed patients (<0.05) and in the control subjects (<0.01), but not in the dialysis patients. According to Study 3, ANP was unchanged during angiotensin II infusion. Blood pressure was increased in all groups during noradrenaline and angiotensin II infusions. It can be concluded that ANP is increased both in patients with chronic renal failure before requirement of dialysis and in patients on maintenance dialysis. It is suggested that noradrenaline stimulates ANP release. [ABSTRACT FROM PUBLISHER]