Captopril-induced changes in MAG3 clearance in patients with renal arterial stenosis and the effect of renal angioplasty.

UNLABELLED: Angiotensin-converting enzyme inhibition by captopril decreases renal (131)I-o-iodohippurate sodium or iothalamate extraction in patients with renal artery stenosis (RAS). This study investigated the effect of captopril on another renal radiopharmaceutical, (99m)Tc-mercaptoacetyltriglycine (MAG3), in particular its plasma clearance. METHODS: Three groups of patients were studied. Group I contained 22 patients with hypertension but a low likelihood of RAS according to negative captopril renography results, confirmed by angiography in 5. Group II contained 22 hypertensive patients with RAS documented by angiography and positive captopril and plasma renin response. Group III contained 10 patients after successful percutaneous transluminal renal angioplasty (PTRA) with negative captopril renography results. The 60-min, single-sample technique was used for measurement of the plasma clearance of MAG3 during baseline and captopril renography. RESULTS: In 18 of 22 group I patients, clearance increased (P < 0.01) during captopril renography compared with baseline conditions, whereas in 18 of 22 group II patients, clearance decreased (P< 0.01). In group III patients, clearance was not significantly altered. The clearance decrease in group II did not correlate with the blood pressure decrease or plasma renin activity increase during captopril renography. CONCLUSION: Renal function assessed by MAG3 plasma clearance decreases in hypertensive patients with RAS but increases in patients without RAS. MAG3 clearance measurements during baseline and captopril renography can thus serve as additional diagnostic information when investigating patients with hypertension for the possibility of an RAS.

Vasoactive agents and blood pressure regulation in sequential ultrafiltration and hemodialysis.

Hypotension is a common and sometimes dangerous side effect of hemodialysis. Its etiology is multifactorial and largely unknown. Earlier studies on the role of endogenous blood pressure regulating agents such as catecholamines and renin have rendered conflicting results. We studied the influence of ultrafiltration and isovolemic hemodialysis separately on the plasma concentrations of the following blood pressure regulating agents: adrenaline, noradrenaline, dopamine, neuropeptide Y, calcitonin gene-related peptide (CGRP), renin (PRA), angiotensin II, vasopressin, aldosterone and cortisol. During isolated ultrafiltration, plasma levels of two strong vasoconstrictors (noradrenaline and angiotensin II) and one strong vasodilator (calcitonin gene-related peptide, CGRP) increased significantly (noradrenaline 3.24 +/- 0.60 nM to 4.31 +/- 0.55 nM; p = 0.032, angiotensin II 19.74 +/- 3.46 pmol/l to 28.49 +/- 7.24 pmol/l; p = 0.047) No symptomatic hypotension occurred. At the end of isovolemic hemodialysis, plasma levels of all the vasoconstricting agents had decreased to pretreatment values, but those of CGRP had continued to rise (from 85.3 +/- 17.6 pmol/l to 114.5 +/- 25.3 pmol/l, p = 0.031). During isovolemic hemodialysis, blood pressure fell to symptomatic levels, but was restored at the end of treatment. The study shows that hemodialysis patients respond to fluid removal by ultrafiltration with an increase in plasma levels of CGRP, noradrenaline and angiotensin II. The net effect is an appropriate vasoconstriction and adequate blood pressure is maintained during isolated ultrafiltration.(ABSTRACT TRUNCATED AT 250 WORDS)

Renal neurohormonal and vascular responses to dynamic exercise in humans.

Effects of graded supine dynamic exercise (30, 60, and 80-90% of maximal physical capacity, i.e., work loads of 69, 132, and 188 W) on renal vascular resistance (RVR); renal sympathetic nerve activity [assessed by the renal venous overflow of norepinephrine (NE)]; renal overflows of dopamine (DA), immunoreactive neuropeptide Y (NPY-LI), and renin; as well as plasma concentrations of angiotensin-(1-8)-octapeptide (ANG II) were evaluated in eight healthy male volunteers. Exercise evoked stimulus-dependent and marked elevations of RVR, arterial NE, epinephrine (Epi), and DA. RVR increased by 140% and the renal overflows of NE and DA increased by 1,331 and 179%, respectively, at 188 W. A net removal of NPY-LI at rest turned into a small net renal overflow, which correlated with increases in RVR at 188 W. Increases in renin release (+1,200% at 188 W) correlated with increases in renal NE and DA overflows and with arterial Epi levels. Arterial ANG II levels increased stimulus dependently (by 264% at 188 W) and correlated more closely with increases in RVR than did other variables. Thus dynamic exercise is a potent stimulus for renal nerve activation in humans, and renal sympathetic nerve activity may contribute to increased RVR both directly (NE and, at exhaustive work loads, possibly NPY) and indirectly (via renin-mediated ANG II formation).

Renal and systemic plasma immunoreactive neuropeptide Y and calcitonin gene-related peptide responses to mental stress and adrenaline in humans.

Arterial plasma levels and renal venous overflows of immunoreactive neuropeptide Y (NPY-LI) and calcitonin gene-related peptide (CGRP-LI) were studied during mental stress (a modified version of Stroop's colour word conflict test--CWT) and during i.v. infusions of step-wisely increasing doses of adrenaline (ADR) in 12 healthy male volunteers. At rest, mean arterial plasma levels of NPY-LI and CGRP-LI were 27 +/- 2 pmol l-1 and 61 +/- 9 pmol l-1, respectively. No renal venoarterial concentration difference could be demonstrated for either peptide at rest. Although CWT caused a three-fold increase in the simultaneously measured renal venous overflow of noradrenaline, indicating markedly increased renal sympathetic nerve activity, the arterial levels of NPY-LI were unchanged and the net renal overflow of NPY-LI was only slightly (not significant) and transiently increased. CWT also failed to influence CGRP-LI levels in arterial plasma or CGRP overflow from the kidney. During ADR infusions, which increased arterial plasma ADR from 0.25 +/- 0.06 to 6.43 +/- 0.27 nmol l-1, NPY-LI levels were unaffected but CGRP-LI levels in arterial plasma were elevated (P less than 0.001 by ANOVA). No net renal overflow of CGRP-LI could, however, be demonstrated. These findings suggest that CWT is not powerful enough a stimulus to significantly enhance systemic or renal overflows of NPY-LI even though marked renal sympathetic activation occurs. During ADR infusions plasma CGRP-LI levels increased but renal veno-arterial differences of CGRP-LI were unaltered, indicating that CGRP-LI may be released from sites other than the kidney by ADR.

Renal responses to lower body negative pressure in humans.

Renal blood flow, renal sympathetic nerve activity, assessed by the renal overflows of norepinephrine (NE), dopamine (DA), and neuropeptide Y-like immunoreactivity (NPY-LI), as well as plasma renin activity and angiotensin II (ANG II) were evaluated during stepwise increases in lower body negative pressure (LBNP) in 10 healthy volunteers. The fractional extraction of epinephrine (Epi) was used to assess renal catecholamine removal (approximately 50%) from arterial plasma. Renal NE, DA, and NPY-LI overflows at rest were 235 +/- 31, 30 +/- 5, and 0.6 +/- 0.2 pmol/min, respectively. LBNP increased renal vascular resistance (RVR) by 52% and renal NE overflow by 31%. Renin release increased by 330% (from 64 +/- 12 units/min) and arterial ANG II levels by 119%, without altering the renal ANG II extraction (which was approximately 50%). Renal DA and NPY-LI overflows were unaffected. A "vaso-vagal" reaction in one subject was associated with cessation of renal NE overflow and marked elevations of arterial Epi, renal renin release, and arterial ANG II. Selective unloading of cardiopulmonary baroreceptors by low-level LBNP did not affect RVR, whereas higher levels of LBNP caused renal vasoconstriction probably mediated in part by increased renal sympathetic nerve activity and in part by ANG II.

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.

Renal responses to mental stress and epinephrine in humans.

Renal blood flow, renal sympathetic nerve activity, and renin release responses to mental stress (Stroop's color-word conflict test; CWT) and intravenously infused epinephrine (Epi) were evaluated in 12 healthy volunteers. The overflows of norepinephrine (NE) and dopamine (DA) to renal venous plasma were measured as indexes of nerve activity; the fractional extraction of Epi was used to assess renal catecholamine extraction from arterial plasma. At rest, NE and DA levels were higher in renal venous plasma than in arterial plasma. Arterial Epi levels were 0.26 +/- 0.04 nmol/l, and the fractional extraction of Epi by the kidney was 46 +/- 4%. CWT increased renal vascular resistance (RVR) by 48%, renal venous NE overflow by 214% (to 708 +/- 79 pmol/min), and DA overflow by 42% (to 34 +/- 4 pmol/min). Arterial Epi increased by 197%. The vasoconstrictor response was correlated with the NE overflow response. The increased renin release (from 75 to 247 U/min, median values; P less than 0.001) was correlated to increases in mean arterial pressure and NE and DA overflows. Epi infusion increased arterial plasma Epi and renin release dose dependently to 6.43 +/- 0.27 nmol/l and by 664%, respectively. RVR and NE and DA overflows were unchanged. Renal venous DA data support the existence of a subset of renal dopaminergic nerves. Mental stress causes renal vasoconstriction, apparently due to increased renal sympathetic nerve activity. Physiological increments of circulating Epi do not affect renal blood flow but enhance renin release markedly without apparent activation of the renal nerves in humans.

Development of hypertension and uraemia after pyelonephritis in childhood: 27 year follow up.

OBJECTIVE: Determination of the long term incidence of uraemia, hypertension, and toxaemia in pregnancy associated with non-obstructive focal renal scarring after pyelonephritis in childhood 25-35 years earlier. DESIGN: 27 Year follow up of patients with non-obstructive focal scarring identified from a retrospective review of intravenous urograms performed in childhood between 1951 and 1967. SETTING: Paediatric primary referral centre and urological clinic in tertiary referral centre. PATIENTS: 30 Patients (mean age 33 (range 22-41] with non-obstructive focal renal scarring first detected between 1951 and 1967 and a history of febrile urinary tract infection. MAIN OUTCOME MEASURE: Hypertension and complications of renal damage. RESULTS: Three patients had developed end stage renal disease, seven had developed hypertension, two of 16 women had a history of toxaemia during pregnancy, and seven patients had undergone renal surgery during follow up. Of the 20 patients who had neither had renal surgery nor had end stage renal disease, all had a significantly lower glomerular filtration rate and renal plasma flow and higher diastolic blood pressure, mean arterial blood pressure, plasma renin activity, and serum beta 2 microglobulin concentration than 13 healthy age matched controls. Diastolic blood pressure and plasma renin activity were positively correlated (r = 0.50, p less than 0.05) and so were fractional sodium excretion and both systolic and diastolic blood pressures (r = 0.54, p less than 0.01, r = 0.51, p less than 0.01 respectively). The progress of renal damage was unrelated to the incidence of recurrent infections. CONCLUSIONS: Children with focal renal scarring due to pyelonephritis are at high risk of serious long term consequences. It is essential that they are given adequate attention and care during adolescence and pregnancy.

Effect of diatrizoate on renal extraction of PAH in man.

The effect of diatrizoate on the renal extraction of para-amino hippurate (EPAH) was studied in 8 healthy male volunteers. The contrast medium was injected into an antecubital vein and into a renal vein in each individual. A single-injection technique for the determination of EPAH was used and EPAH was measured before and over a period of 30 min after each contrast medium injection. In addition, the renal extraction of diatrizoate was measured simultaneously. Small but significant and similar decreases in EPAH were observed after both antecubital and renal venous administrations of the contrast medium, with a duration of less than 30 min after the injection. The renal extraction ratio for the diatrizoate was 0.20. It is concluded that diatrizoate should not be used before the determination of EPAH, at least not until 30 min after the administration of the contrast medium. The decrease in EPAH caused by diatrizoate seems to be due to a direct tubular depressant effect.

Reflex activation of renal nerves in humans: differential effects on noradrenaline, dopamine and renin overflow to renal venous plasma.

Using a thermodilution technique for renal venous blood flow measurements, renal sympathetic nerve activity was evaluated in 10 healthy volunteers by measurements of noradrenaline (NA) and dopamine (DA) overflow to renal venous plasma. Renin release was measured simultaneously. At rest, arterial adrenaline (ADR) levels were 0.24 +/- 0.03 nmol-1 and NA and DA levels were higher in renal venous than in arterial plasma (1.24 vs. 0.98 and 0.14 vs. 0.09 nmol l-1, respectively, P less than 0.01 for both). The renal extraction of ADR from arterial plasma was 40 +/- 4%. ADR extractions were used to correct for the renal removal of NA or DA from arterial plasma when calculating the renal overflow of NA or DA to renal venous plasma. At rest, the thus corrected renal venous overflows of NA and DA were 228 +/- 34 and 29 +/- 3 pmol min-1, respectively. Isometric handgrip exercise (IHG) increased renal vascular resistance (RVR) by 20% and NA overflow by 123%, without altering renin release or DA overflow. Vasodilatation induced by dihydralazine (HYDR) increased NA overflow by 63% (P less than 0.05) and elevated DA overflow by 107 +/- 59%. The renal DA/NA overflow ratio was reduced from 0.15 to 0.06 (P less than 0.01) during IHG, but was not altered by HYDR. Renin release increased by 377% after HYDR (P less than 0.001) and was correlated to the reduction of mean arterial pressure but not changes in NA overflow. Thus, both IHG and HYDR increased renal sympathetic nerve activity, although differential effects on renin release and DA overflow were observed. The dissociation of renal NA and DA responses suggests that the human kidney may have a subset of dopaminergic nerves.

Plasma renin activity and oxygen content along the renal veins in hypertensive patients.

Plasma renin activity (PRA) and oxygen content in three different locations in the renal veins were studied in 27 patients with suspected renin-dependent hypertension or during post-operative follow-up investigations after renal artery reconstruction. A significant decrease in PRA was found along the right renal vein but not along the left one. The oxygen content simultaneously measured was lower in the central parts of both renal veins than most peripherally, more on the right side than on the left one, indicating dilution of renal venous blood. An erroneous ratio between renal vein PRA of the affected and the contralateral kidney was found in two of 17 patients with unilateral renal artery stenosis when sampling from a central position in the renal vein. This indicates that a peripheral position of the catheter is important when sampling for renal vein PRA.

Psychosocial and physiological factors in relation to blood pressure at rest--a study of Swedish men in their upper twenties.

The interrelationships between psychosocial factors, several physiological variables and blood pressure (BP) were investigated in 88 young men (aged 26-32 years) in whom high, intermediate or low BP had been recorded at the age of 18 years. In the original high BP group, venous plasma noradrenaline was normal but adrenaline levels elevated. At the follow-up adrenaline correlated with systolic blood pressure (SBP), and this was also so after controlling for overweight and serum gamma-glutamyltranspeptidase [gamma-GT, a marker for alcohol consumption, which showed an independent association with diastolic blood pressure (DBP)]. Low assertiveness (low scores of verbal and indirect aggression) correlated with high BPs, even after controlling for other psychosocial variables. Several associations between psychosocial job variables and physiological variables were found. Among self-reported job variables, excessive 'demands' and 'bossing others' (but not 'decision latitude' or 'psychosocial conflict') were associated with high SBP. Habitual smoking of cigarettes was not associated with BP at rest, but influenced several associations between psychosocial and physiological variables. Men with high BP at rest and low plasma renin activity (PRA) reported more psychosocial problems at work and lower assertiveness than other groups.

Effect of the contrast medium meglumine amidotrizoate on renal extraction of para-amino hippurate after injection into the renal vein.

The effect of the contrast medium meglumine amidotrizoate (AngiografinR) on the renal extraction of para-amino hippurate (EPAH) was studied in 24 patients with suspected or previous renin-dependent hypertension. A single injection technique for administration of PAH was used and in eight additional patients the relationship between the arterial concentration of PAH and EPAH was studied over a period of 30 min after the injection. No change in EPAH with decreasing arterial concentration of PAH was found. After injection of 26 g of contrast medium (40 ml) into the renal veins of 18 of the 24 patients, a small (6%) but significant decrease in EPAH was observed. There was no significant difference in the decrease in EPAH between kidneys with increased and normal renal vein plasma renin activity. In the remaining six patients, the contrast medium (20 ml) was injected into one renal vein only, and blood samples were repeatedly drawn from both kidneys over a period of 30 min after injection. A decrease in EPAH was observed in both the injected and contralateral kidney; the decrease lasted for at least 20 min, with a maximum 1 min after injection. It is concluded that meglumine amidotrizoate injected into the renal vein causes a reduction of EPAH. Therefore, a contrast medium such as meglumine amidotrizoate should be avoided before determining the renal extraction of PAH.

Renin release during controlled hypotension with sodium nitroprusside, nitroglycerin and adenosine: a comparative study in the dog.

The haemodynamic effects of i.v. infusions of sodium nitroprusside (SNP), nitroglycerin (TNG), and adenosine were studied in dogs in parallel with quantitative determinations of plasma renin activity (PRA) by radioimmunoassay. The drugs were given for controlled hypotension, and the mean arterial blood pressure (MABP) was decreased to approximately 50 mmHg (6.7 kPa). Arterial blood samples for PRA were collected at 10-min intervals. During the last interval the dogs were subjected to haemorrhagic shock. SNP-induced hypotension could be maintained only with a stepwise increase in infusion rate, from 11.8 to 16.0 micrograms X kg-1 X min-1 (P less than 0.05). TNG could not produce the desired blood pressure level, but gradually increasing doses induced a gradually decreasing MABP (80-60 mmHg) (10.7-8.0 kPa). During adenosine-induced hypotension, a perfectly stable blood pressure level was maintained without dose adjustments. Both SNP and TNG induced blood pressure-dependent increases in PRA, while no changes in PRA were seen during adenosine-induced hypotension. Nor could haemorrhagic shock, which induced further increases in PRA during SNP- and TNG-induced hypotension, alter PRA during adenosine infusions. We conclude that adenosine differs markedly from conventional hypotensive drugs such as SNP and TNG with respect to stability of action and dose requirements, and that this stability is related to an inhibited increase in renin release.

Persisting hypertension after renal artery reconstruction. A follow-up study.

Twenty-four patients with persisting hypertension after renal artery reconstruction were re-investigated 1--8 years after surgery. They underwent renal arteriography, determination of plasma renin activity, renography and renal function studies in order to find the causes of the postoperative hypertension. Restenosis was found in 6 patients, in 3 of whom it was of functional significance according to the positive renin tests (renin ratio greater than 1.5). Positive renin tests were found in 2 other patients. One had occlusion of a renal artery branch and the other hypoplasia of the kidney due to chronic nephritis. No explanation of the persisting hypertension could be found in 19 patients at re-examination. In 10 of them, however, biopsy from the affected kidney obtained during operation showed nephrosclerosis, which may explain the outcome. Fourteen of the 19 patients had negative renin tests preoperatively. These negative tests indicate that renal artery stenosis was not the only cause of hypertension. It may be concluded that the renin test is of the utmost value in the selection of patients for renal artery reconstruction and should always be considered. A biopsy from the contralateral kidney may be necessary in order to detect other causes of hypertension than renal artery stenosis. The importance of re-investigating patients with persisting hypertension is confirmed by the present study.

Renal artery reconstruction in renovascular hypertension.

Over a period of 8 years, 52 patients (31 females and 21 males) between 12 and 59 years of age (mean age 40 years) underwent renal artery reconstruction for correction of renovascular hypertension. Five patients were operated on bilaterally. A thoracoretroperitoneal approach was chosen at 48 of 57 renal artery reconstructions. The most used types of arterial reconstruction were thrombendarterectomy and vein patch, resection of the stenosis and end-to-end anastomosis, vein patch only or aortorenal vein bypass. No early or late nephrectomies were performed. These was no operative mortality, but 3 late deaths occurred. Twenty-two patients were normotensive postoperatively, 20 were improved and there were 10 failures. The follow-up time as 1--8 years. The blood pressures were measured after withdrawal of antihypertensive drugs for at least 10 days. The best predictable criterion for normotension was a positive renin test with a renin ratio of 1.5 or more. The normotensive patients were in the younger age group with a shorter duration of known hypertension and had mainly fibromuscular hyperplasia.