Reduction in blood product usage associated with routine use of mini bypass systems in extracorporeal circulation.

OBJECTIVE: The objective of this study is to investigate the hypothesis that a reduced prime extracorporeal circulation (ECC) system and ensuing reduction in patient hemodilution can affect blood product use. METHODS: We performed a prospective, randomized study from a group of 60 consecutive coronary artery bypass graft (CABG) patients, comparing blood product usage and postoperative bleeding in 30 mini bypass systems (n = 30) to 30 conventional systems (n = 30). The patient demographics in terms of patient weight, height, age, preoperative hemoglobin, preoperative hematocrit, BSA, ejection fraction, and NYHA were not statistically significant. RESULTS: Blood product use, including fresh frozen plasma (FFP) and homolgous blood transfusions was tracked through the operating theater and into the intensive care unit. In the mini bypass group, while no homologous blood transfusions were given in the OR, 27% of the patients received at least one unit of homologous blood. In the control group, 43% of the patients received at least one unit of blood in the OR or in the ICU and there was a stastistically-significant 38% reduction in homologous blood product use (p = 0.05). For the patients who received homologous blood, there was also a significant reduction in transfused volume (0.53 +/- 0.90 units blood mini bypass vs 1.3 +/- 1.93 units conventional, p < 0.05). In terms of FFP, there was also a stastistically significant difference between the two groups (0 units transfused in mini bypass group vs 3 patients receiving one unit FFP in the control group, p < 0.001). Cumulative postoperative bleeding during the ICU stay was also evaluated, yielding a significant reduction (365 +/- 495 ml mini bypass vs 825 +/- 975 ml conventional, p < 0.05). CONCLUSION: Mini bypass reduces on-pump hemodilution and, therefore, donor blood usage in routine CABG patients as compared to conventional ECC circuits and can reduce postoperative bleeding as compared to a traditional system. The mini bypass system is safe in routine clinical use and can manage easily the same number of anastomoses as a traditional system and should be considered a favorable alternative to conventional ECC in all revascularization cases.

Impaired basal NO activity in patients with glomerular disease and the influence of oxidative stress.

Endothelial dysfunction has been found to be linked to and predictive of cardiovascular events. Whether endothelial function of the renal vasculature is impaired in patients with chronic glomerular disease and whether oxidative stress is of importance in this setting has not yet been determined. In this study, endothelial function of the renal vasculature was investigated in 25 patients with chronic glomerular disease and 50 control subjects matched for age and blood pressure. Renal plasma flow (RPF) and glomerular filtration rate were measured by constant infusion input clearance technique at baseline and following infusions of the nitric oxide synthase (NOS) inhibitor N(G)-monomethyl-L-arginine (L-NMMA, 4.25 mg/kg), the substrate of NOS L-arginine (100 mg/kg) and the antioxidant vitamin C (3 g co-infused with L-arginine 100 mg/kg). At baseline, RPF was similar in the two groups. The reduction in RPF in response to L-NMMA was less pronounced in patients with chronic glomerular disease compared to control subjects (-4.6+/-12 vs -9.8+/-9%; P=0.040), indicating reduced basal nitric oxide (NO) activity in chronic glomerular disease. Co-infusion of the antioxidant vitamin C on top of L-arginine induced a more pronounced increase in RPF in patients with chronic glomerular disease than in control subjects (21.7+/-17 vs 10.9+/-22%; P=0.036). Our findings suggest that basal NO activity of the renal vasculature is reduced in patients with chronic glomerular disease compared to age- and blood pressure-matched control subjects. This might be in part related to increased oxidative stress.

Impaired sodium excretion during mental stress in mild essential hypertension.

In hypertensive rats, environmental stress causes sodium retention by an exaggerated increase in renal sympathetic nerve activity, which is modulated by angiotensin II. We tested whether similar effects can be observed in humans. In 66 normotensive subjects (half of them with a family history of hypertension) and 36 subjects with mild essential hypertension, urinary sodium excretion and renal hemodynamics were examined at rest and during mental stress treated either with placebo or ACE inhibition in a double-blind, randomized, cross-over design. Despite a marked increase in glomerular filtration rate in response to mental stress (Deltaglomerular filtration rate, 4.3+/-7.7 mL/min in normotensives without versus 5.6+/-8.4 mL/min in normotensives with a family history versus 10.1+/-5.7 mL/min in patients with mild essential hypertension; P:<0.002), the increase in urinary sodium excretion was blunted in patients with mild essential hypertension (Deltaurinary sodium excretion, 0.12+/-0.17 mmol/min versus 0.10+/-0.14 mmol/min versus 0.05+/-0.14 mmol/min; P:<0.05). ACE inhibition corrected the natriuretic response to mental stress in subjects with mild essential hypertension (Deltaurinary sodium excretion, 0.05+/-0.14 mmol/min with placebo versus 0.13+/-0.19 mmol/min with ACE inhibition; P:<0.01); thus, after ACE inhibition, urinary sodium excretion increased similarly in all 3 groups. In conclusion, impaired sodium excretion occurs during mental stress in human essential hypertension but not in subjects with positive family history of hypertension. This abnormality in sodium handling during activation of the sympathetic nervous system appears to be mediated by angiotensin II.

Regression of left ventricular hypertrophy by AT1 receptor blockade in renal transplant recipients.

AT1 receptor antagonists control blood pressure (BP) effectively and reduce left ventricular hypertrophy in patients with essential hypertension. Because left ventricular hypertrophy is very common in renal transplant recipients, we examined the cardiovascular effects and the safety profile of the AT1 receptor antagonist losartan in hypertensive renal transplant recipients. In 20 renal transplant recipients with stable renal graft function 50 mg of losartan was added to the preexisting antihypertensive treatment (no angiotensin-converting enzyme inhibitors) at least 6 months after renal transplantation. Twenty-four-hour ambulatory BP, two-dimensional-guided M-mode echocardiography, and duplex sonography, as well as renal function, red blood cell count, cyclosporine A and FK 506 levels, erythropoetin, and angiotensin II concentration were determined at baseline and after 6 months of therapy. With 24-h ambulatory BP measurement, systolic blood pressure (SBP) was reduced by 7.5 +/- 2.4 mm Hg and diastolic blood pressure (DBP) by 4.5 +/- 1.8 mm Hg (P < .01 and P < .05, respectively). Posterior, septal, and relative wall thickness decreased by 0.95 +/- 0.2 mm, 0.91 +/- 0.2 mm and 0.04 +/- 0.01 mm, respectively (all P < .001). Left ventricular mass index decreased by 18.1 +/- 4.7 g/m2 (P < .01). Ejection fraction and midwall fractional fiber shortening as systolic parameters and the relation of passive-to-active diastolic filling of the left ventricle were unaltered. Serum creatinine and cyclosporine A concentration remained stable in all patients. Hemoglobin and hematocrit decreased by 1.0 +/- 0.3 g/dL and 3.6% +/- 0.9%, respectively (P < .002 and P < .001) without a change in serum erythropoetin level. In renal transplant recipients the AT1 receptor antagonist losartan reduces left ventricular hypertrophy without altering systolic or diastolic function. It is safe with regard to renal function and immunosuppression, but slightly decreases hemoglobin level.

Enhanced antinatriuresis in response to angiotensin II in essential hypertension.

Angiotensin II regulates sodium homeostasis by modulating aldosterone secretion, renal vascular response, and tubular sodium reabsorption. We hypothesized that the antinatriuretic response to angiotensin II is enhanced in human essential hypertension. We therefore studied 48 white men with essential hypertension (defined by ambulatory blood pressure measurement) and 72 normotensive white control persons, and measured mean arterial pressure, sodium excretion, renal plasma flow, glomerular filtration rate, and aldosterone secretion in response to angiotensin II infusion (0.5 and 3.0 ng/kg/min). Hypertensive subjects exhibited a greater increase of mean arterial pressure (16.7+/-8.2 mm Hg v 13.4+/-7.1 mm Hg in normotensives, P < .05) and a greater decrease of renal plasma flow (-151.5+/-73.9 mL/ min v -112.6+/-68.0 mL/min in controls, P < .01) when 3.0 ng/kg/min angiotensin II was infused. The increase of glomerular filtration rate and serum aldosterone concentration was similar in both groups. Sodium excretion in response to 3.0 ng/kg/min angiotensin II was diminished in both groups (P < .01). However, the decrease in sodium excretion was more pronounced in hypertensives than in normotensives (-0.18+/-0.2 mmol/min v -0.09+/-0.2 mmol/min, P < .05), even if baseline mean arterial pressure and body mass index were taken into account (P < .05). We conclude that increased sodium retention in response to angiotensin II exists in subjects with essential hypertension, which is unrelated to changes in glomerular filtration rate and aldosterone concentration. Our data suggest a hyperresponsiveness to angiotensin II in essential hypertension that could lead to increased sodium retention.

Plasma endothelin is increased in early essential hypertension.

Local vascular generation of endothelin-1 (ET-1) may contribute to elevated peripheral resistance in hypertension. We tested the hypothesis that immunoreactive ET production in the forearm circulation is increased in early essential hypertensive subjects. Ten young, previously untreated male patients with mild essential hypertension and no signs of target organ damage were compared with matched normotensive subjects in an outpatient setting. Arterial and venous samples were obtained from indwelling catheters in the brachial artery and the medial cubital vein, respectively. Samples were collected at baseline and after induction of endothelium-dependent (acetylcholine) vasodilation. Immunoreactive ET (ET) was measured after column extraction by a sensitive radioimmunoassay employing a C-terminal ET-1 antibody with negligible cross-reaction to big-ET. Individual recovery rates were determined for each sample. Basal ET was significantly higher in hypertensive than in normotensive subjects, both in venous and arterial samples (P < .01). This difference was also present after correction for recovery (P < .01). There was no significant difference between venous and arterial ET concentrations. Local vasodilation did not change arterial or venous ET levels. In conclusion, plasma ET is increased in young, untreated, essential hypertensive subjects with no signs of target organ damage. The increased circulating immunoreactive ET may point to a role for the peptide early in the development of high blood pressure.

Relation between the renin-angiotensin-aldosterone system and left ventricular structure and function in young normotensive and mildly hypertensive subjects.

BACKGROUND: High angiotensin II levels in relation to the corresponding urinary sodium excretion have been found to modulate left ventricular (LV) structure in middle-aged hypertensive patients. To analyze whether such a relation between the renin-angiotensin-aldosterone system and left ventricular structure is already present in young individuals, we examined the changes of angiotensin II and aldosterone in response to increased salt intake and their relations to LV structure and function. METHODS: In 119 young (aged 26 +/- 3 years) patients with normal or mildly elevated blood pressure, we determined LV structure and function (2-dimensional guided M-mode echocardiography and pulse wave Doppler sonography) and 24-hour ambulatory blood pressure (SpaceLabs 90207). Dietary sodium intake as estimated by 24-hour urinary sodium excretion, plasma renin activity, angiotensin II, and aldosterone concentrations were measured first on a normal diet and second at high salt intake to determine the extent of the resulting suppression of the renin-angiotensin-aldosterone system. RESULTS: Body mass index (r = 0.43, P <.001) and both systolic (r = 0.24, P <. 01) and diastolic (r = 0.19, P <.05) 24-hour ambulatory blood pressure correlated with LV mass. No straightforward relation was found between LV structure and baseline angiotensin II or aldosterone concentration. The increase of sodium excretion at high salt intake was related to a physiologically expected decrease of angiotensin II and aldosterone levels in normotensive (r = -0.36, P <.01 and r = -0.32; P =.016, respectively) but not in hypertensive patients. Changes in angiotensin II or aldosterone concentration were not related to LV structure in either hypertensive or normotensive young individuals. However, changes in aldosterone secretion correlated with diastolic filling parameters in hypertensive patients (velocity-time integrals of the A over E wave: r = 0.32, P =.03; atrial contribution of LV filling: r = 0.33, P =. 025) but not in normotensive individuals. CONCLUSION: In contrast to middle-aged hypertensive patients, neither angiotensin II, aldosterone, nor their suppression in response to high salt intake were related to LV structure in young hypertensive patients. However, inadequate suppression of aldosterone after salt intake was associated with diastolic filling abnormalities in our young hypertensive patients, which may represent early changes in hypertensive heart disease and precede potential structural alterations.

Presence of factor-VII and -XIII activity in ultrafiltrate during hemofiltration.

UNLABELLED: Bleeding complications during renal replacement therapies can be attributed to coagulation system and platelet function alterations in uremia, and the application of heparin in extracorporeal circulation. Small protein losses during hemofiltration are always described, however the high molecular weight of coagulation factors should significantly prevent their removal during hemofiltration. To exclude degradation of coagulation factors under conditions of spontaneous ultrafiltration, the hemofiltrate of 40 patients with acute renal failure (treated with continuous veno-venous hemofiltration, CVVH) was sampled from the filtrate line after 1 h from the beginning of treatment and in 5 patients also after 12 and 24 h. Samples were investigated with human factor deficient plasma (VII, X, XI, XII) from donors with a congenital deficiency and with human plasma depleted of factor V, VIII, IX, and protein S and C. Factor XIII was detected photometrically. Subsequently the presence of factor- XIII and -VII activity was investigated in plasma and hemofiltrate from 16 patients treated with intermittent hemofiltration before (plasma) and after (plasma, hemofiltrate) therapy. These patients also suffered from acute renal failure and needed renal replacement therapies. Quality control was carried out with a buffer solution (<1% activity in the assays according to recommended protocols). RESULTS: Factor-V, -VIII, -IX, -X, -XI, and -XII activity, and protein C and S could not be detected in the hemofiltrate from continuous hemofiltration. Factor-VII and -XIII activity was present in the hemofiltrate (mean activity in CVVH: 1.93% for factor VII and 6.9% for factor XIII, mean activity in intermittent hemofiltration: <1% for factor-VII and 7.3% for factor-XIII). Three were no significant differences (Student's t-test) in plasma activity before and after intermittent hemofiltration of factor VII (44 vs. 47%, p = 0.39) and factor XIII (44 vs. 52%, p = 0.24). The presence of factor-VII and -XIII activity in the hemofiltrate cannot influence plasma activities in intermittent hemofiltration. Rapid new synthesis and short half-life should neutralize these effects. Elimination of coagulation factor-XIII activity should be excluded by the next generation of highly permeable membranes and on-line hemodiafiltration.

Hyper-responsiveness to angiotensin II is related to cardiac structural adaptation in hypertensive subjects.

BACKGROUND: Angiotensin II has been found to be a growth stimulating factor for myocardial cells. In humans, angiotensin II infusion causes vasoconstriction in systemic and renal vasculature and leads to aldosterone secretion. Our hypothesis was that hyper-responsiveness to angiotensin II is related to left ventricular mass in human essential hypertension. METHODS AND RESULTS: In 30 normotensive individuals and 30 subjects with mild essential hypertension (white men, mean age 26+/-3 years), the responsiveness to angiotensin II was assessed by measuring changes in mean arterial pressure, renal blood flow, glomerular filtration rate and aldosterone secretion in response to i.v. angiotensin II infusion (0.5 and 3.0 ng/kg per min). The provoked changes to angiotensin II infusion were similar in the normotensive and hypertensive group with the exception of an exaggerated increase in mean arterial pressure in hypertensives (14+/-5 versus 10+/-5 mm Hg, P<0.001 at 3.0 ng/kg per min angiotensin II). The increase in mean arterial pressure was correlated with left ventricular mass in hypertensive subjects (angiotensin II 0.5 ng/kg per min: r = 0.49, P<0.005; angiotensin II 3.0 ng/kg per min: r = 0.35, P<0.05); no such correlation was found in the normotensive group. After taking into account baseline mean arterial pressure and body mass index, the increase in mean arterial pressure to angiotensin II 0.5 ng/kg per min was still correlated with left ventricular mass (partial r = 0.50, P<0.01). Similarly, the change of glomerular filtration rate but not of renal blood flow in response to angiotensin II 0.5 ng/kg per min was correlated with left ventricular mass, (r = 0.42, P<0.02) in the hypertensive group but not in the normotensive one. This relationship remained significant even after taking baseline glomerular filtration rate, mean arterial pressure and body mass index into account (partial r = 0.43, P<0.05). CONCLUSION: Hyper-responsiveness to angiotensin II is related to an increased left ventricular mass in hypertensive subjects independent of blood pressure.

Low-density lipoprotein-cholesterol determines vascular responsiveness to angiotensin II in normocholesterolaemic humans.

OBJECTIVE: Both LDL-cholesterol and angiotensin II have been shown to increase the risk for and severity of cardiovascular disease. In hypercholesterolaemia, experimental studies have demonstrated an increased angiotensin type 1 (AT1) receptor expression on vascular smooth muscle cells and an increased vascular responsiveness to vasopressors has been documented in humans. We investigated in a normocholesterolaemic young population whether vascular responsiveness to angiotensin II (Ang II) infusion depends on LDL-cholesterol serum levels in the systemic and renal circulation. DESIGN AND METHODS: Changes in systolic and diastolic blood pressure (deltaBP) to Ang II infusion (0.5 and 3.0 ng/kg per min) were investigated in 103 normocholesterolaemic (LDL-cholesterol < 160 mg/dl) young white men (26+/-3 years; 24 h BP: 128+/-10/75+/-7 mmHg) without cardiovascular disease. According to their LDL-cholesterol levels, participants were classified into tertiles (lower tertile < 85 mg/dl, middle tertile 85-111 mg/dl, upper tertile > 111 mg/dl). RESULTS: Blood pressure (BP) responses to Ang II infusion 3.0 ng/kg per min were enhanced in the group with the highest LDL-cholesterol levels (delta systolic BP: +12.8+/-6.7, +13.2+/-8.6, +17.9+/-9.6, P < 0.02; delta diastolic BP: +11.1+/-5.8, +11.5+/-6.5, +16.5+/-8.3, P < 0.01, for the lower, middle and upper tertiles, respectively). This holds true when baseline BP was taken into account as a confounding covariable (P < 0.015). BP responses to Ang II infusion were related to LDL-cholesterol serum levels (delta systolic BP: r = 0.26, P = 0.01; delta diastolic BP: r = 0.32, P = 0.001). In multiple stepwise regression analysis, LDL-cholesterol emerged as the strongest determinant of vascular responsiveness to Ang II (delta systolic BP: P < 0.01; delta diastolic BP: P < 0.001). CONCLUSION: In young male subjects, responsiveness to Ang II is determined by the LDL-cholesterol serum level even in the normal range of LDL-cholesterol, thereby potentially contributing to the cardiovascular risk of LDL-cholesterol even within the so-called normal range.

Update on reversal of left ventricular hypertrophy in essential hypertension (a meta-analysis of all randomized double-blind studies until December 1996).

OBJECTIVE: To provide an update on the ability of different antihypertensive drugs to reduce left ventricular hypertrophy in essential hypertension. DATA SOURCES: Relevant medical databases including MEDLINE, BIOSIS PREVIEWS, EMBASE, and SCISEARCH as well as review articles to December 1996. STUDY SELECTION: Meta-analysis of all published articles including only double-blind, randomized, controlled clinical studies with parallel-group design. DATA EXTRACTION: Literature search and data extraction according to a prefixed scheme performed independently by two investigators. The primary parameter was reduction of left ventricular mass by antihypertensive therapy with placebo, diuretics, beta-blockers, calcium channel blockers, or ACE-inhibitors. DATA SYNTHESIS: Fifty studies published till the end of December 1996 were identified. They comprised a total of 1715 patients in 13 placebo (n=165, age: 50+/-3 years) and 89 active treatment arms (n=1550, age: 56+/-10 years) respectively. Overall, for active treatment left ventricular mass index was the more reduced the greater the decrease in systolic blood pressure, (r=0.27; P<0.05), the longer the duration of therapy (r=0.36; P<0.001), and the higher the pretreatment value of left ventricular mass index (r= 0.53; P<0.001). Left ventricular mass index was decreased by 12% with ACE-inhibitors (95% CI: 9.0-14.5%), by 11% with calcium channel blockers (95% CI: 7.8-13.7%), by 5% with beta-blockers (95% CI: 1.2-7.3%) and by 8% with diuretics (95% CI: 3.9-11.1%) (overall P<0.01). Subsequent tests revealed that ACE-inhibitors and calcium channel blockers were more effective than beta-blockers in reducing left ventricular mass index (P<0.05). Similar differences between drug classes were found with regard to effect on left ventricular wall thickness (P<0.05). CONCLUSIONS: Decrease in systolic blood pressure, duration of antihypertensive therapy, degree of pretreatment left ventricular hypertrophy and antihypertensive drug class determined the reduction of left ventricular hypertrophy. ACE-inhibitors and calcium channel blockers were more potent in reducing left ventricular mass than beta-blockers, with diuretics in the intermediate range.

Reversal of left ventricular hypertrophy in essential hypertension. A meta-analysis of randomized double-blind studies.

OBJECTIVE: To determine the ability of various antihypertensive agents to reduce left ventricular hypertrophy, a strong, blood pressure-independent cardiovascular risk factor, in persons with essential hypertension. DATA SOURCES: MEDLINE, DIMDI, RINGDOC, ADES, EMBASE, and review articles through July 1995 (English-language and full articles only). STUDY SELECTION: Meta-analysis of all published articles including only double-blind, randomized, controlled clinical studies with parallel-group design. DATA EXTRACTION: Intensive literature search and data extraction according to a prefixed scheme performed independently by 2 investigators. Reduction of left ventricular mass index after antihypertensive therapy with placebos, diuretics, beta-blockers, calcium channel blockers, or angiotensin-converting enzyme (ACE) inhibitors was the principal parameter. DATA SYNTHESIS: Of 471 identified references describing the effects of antihypertensive drugs on left ventricular hypertrophy, only 39 clinical trials fulfilled the inclusion criteria of our study. We found that the decrease in left ventricular mass index was more marked the greater was the decline in blood pressure (systolic r=0.46, P<.001; diastolic r=0.21, P=.08) and the longer was the duration of therapy (r=0.38, P<.01). After adjustment for different durations of treatment (mean duration of treatment, 25 weeks), left ventricular mass decreased 13% with ACE inhibitors, 9% with calcium channel blockers, 6% with beta-blockers, and 7% with diuretics. There was a significant difference between drug classes (P<.01): ACE inhibitors reduced left ventricular mass more than beta-blockers (significant, P<.05) and diuretics (tendency, P=.08). Similar differences between drug classes were found with regard to effect on left ventricular wall thickness (P<.05). CONCLUSIONS: The database of articles published through July 1995 is small and incomplete, and most of the articles are of poor scientific quality. In this first meta-analysis including only double-blind, randomized, controlled clinical studies, decline in blood pressure, duration of drug treatment, and drug class determined the reductions in left ventricular mass index. The ACE inhibitors seemed to be more potent than beta-blockers and diuretics in the reduction of left ventricular mass index; calcium channel blockers were somewhat in the intermediate range. The ACE inhibitors and, to a lesser extent, calcium channel blockers emerged as first-line candidates to reduce the risk associated with left ventricular hypertrophy.

Normalization of circadian blood pressure profiles after renal transplantation.

Most patients with secondary hypertension due to renal disease or on maintenance hemodialysis have lost the physiologic fall of blood pressure during sleep. To test the notion that kidney transplantation normalizes the blood pressure profile, we monitored ambulatory blood pressure over 24 hr in 45 patients (29 males and 16 females) after successful renal transplantation. The longer the time after renal transplantation, the more marked was the decrease of blood pressure during sleep (r = 0.38, P < 0.01). This effect of time after renal transplantation on the fall of blood pressure during sleep was independent of the prevailing level of 24-hr ambulatory blood pressure. The prevalence of dippers (defined by a fall in mean blood pressure during sleep of 10% or more of the awake mean) increased from 27% in the early phase (< 7 months) to 73% in the late phase (> or = 1 year) after renal transplantation (P < 0.01). Again, this effect was not attributable to the level of 24-hr ambulatory blood pressure and concomitant antihypertensive or immunosuppressive medication. We conclude that renal transplantation leads to a normalization of the circadian blood pressure profile with a marked decrease of blood pressure during sleep. As a consequence, the lower hemodynamic load imposed on the cardiovascular system may in turn lead to a reduction of cardiovascular morbidity and mortality.

Natriuresis-pressure relationship in polycystic kidney disease.

We studied, under outpatient conditions, nine patients with autosomal dominant polycystic kidney disease who were hypertensive on their usual diet, and nine normotensive healthy probands. The subjects were examined in random order on the 7th day after equilibration on a low-sodium diet (20 mmol/day) and again on the 7th day after equilibration on the same diet but with added sodium to yield a final intake of 200 mmol/day (or vice versa). Blood pressure was monitored non-invasively for 2 h at 4-min intervals using an automatic system. In healthy probands, mean arterial pressure (MAP) was similar on the low- and the high-sodium diets (92.7 versus 91.9 mmHg). In hypertensive patients, a significant (P less than 0.02) increase in mean MAP (107.2 versus 111.2 mmHg) and in systolic blood pressure (140.6 versus 148.7 mmHg) was observed irrespective of whether the glomerular filtration rate (GFR) was normal or reduced. The natriuresis pressure curve showed an upward shift (resetting) and a positive slope (sodium sensitivity). Patients with a reduced GFR as shown by inulin clearance differed from probands and patients with a normal GFR, by showing greater proportional changes in GFR and body weight. In hypertensive patients, atrial natriuretic factor (ANF) levels were higher at baseline and showed an exaggerated response to sodium loading. Changes in angiotensin II (Ang II) or in Ang II binding sites on platelets were similar in patients and controls and changed appropriately with the sodium intake. These data show a resetting of the natriuresis-blood pressure relationship and an increased blood pressure sensitivity to sodium in hypertensive patients with adult, dominant, polycystic kidney disease.