Plasma Immunoreactive Renin Research Articles

A rare cause of systemic hypertension in an African child: Questions

A female toddler was referred to our hospital with the problem of hypertensive encephalopathy manifesting with convulsions, right hemiparesis and blindness. She had been well until the age of 17 months when she developed fever and symptoms of an upper respiratory tract infection. Her past medical history was significant only for having been a small for gestational age baby. She weighed 2 kg at birth after a term, uncomplicated pregnancy. She had achieved her milestones normally up to the age of 12 months. Thereafter her mother noticed that her neurological development was faltering—she was not talking or playing, she was disinterested in her environment and she was unusually irritable. She has no family history of hypertension, heart or kidney disease. She has one healthy sibling. On physical examination she appeared chronically ill. She was severely stunted (length 72.5 cm, Z score<−3 SD) and wasted (weight for length Z score<−3 SD). Her level of consciousness was depressed. All her pulses were present and normal and there was no radio-femoral delay. Her blood pressure was 148/92 mm Hg and was elevated in all four limbs. She had puffy eyes, but no pedal or sacral oedema. She was clinically anaemic and mildly dehydrated. She did not have any lymphadenopathy. There were no cafe au lait spots, no malar rash and no evidence of vasculitis. The left precordium was bulging. The apex was heaving in the fifth intercostal space, displaced laterally. The second heart sound was loud. There was no murmur over the heart, the subclavian or carotid vessels, over the inter-scapular area or abdominal aorta. There was weakness of the left arm and leg, and all tendon reflexes were markedly brisk. She had complete loss of vision, but her other cranial nerves were intact. Fundoscopy revealed retinal haemorrhages, but no papilloedema. Laboratory investigations revealed the following information: she had a hypokalaemic metabolic alkalosis; potassium was 2.8 mmol/l and bicarbonate was 30 mmol/l. The serum sodium, chloride, urea and creatinine levels were normal. The full blood count showed a hypochromic microcytic anaemia, with haemoglobin of 9.4 g/dl [normal 11.1–14.7 g/dl, mean corpuscular volume of 65.9 fl (normal 70–86 fl) and mean corpuscular haematocrit of 20.8 pg (normal 23–31 pg)]. The differential white cell count was normal. Further investigations showed a suppressed plasma immuno-reactive renin of <1.8 mIU/l (normal 5.4–28.8 mIU/l) and aldosterone level of <31 pmol/l (normal 28–666 pmol/l). The urine potassium was 21.7 mmol/l, urine sodium was <10 mmol/l and urine chloride was 20 mmol/l. The urine protein creatinine ratio was 0.23 g/mmol (normal <0.02 g/mmol). Steroid chromatography excluded endocrine causes of hypertension associated with hypokalaemic metabolic alkalosis. The kidney sonography showed normal-sized kidneys for her length of 72.5 cm (right 6.1×3.1 cm, left 5.8×3 cm), with decreased cortico-medullary differentiation. Renal The answers to these questions can be found at http://dx.doi.org/10.1007/ s00467-013-2446-3

The rennin???angiotensin system

We investigated the effects of the human renin inhibitor, ES-8891, and captopril on renal renin secretion and storage in the marmoset. Either ES-8891 (30mg/kg) or captopril (2 mg/kg) was given orally twice a day for 1 week to conscious, sodium-depleted marmosets (n=6 for each group). The ES-8891-treated group displayed a significant reduction in mean arterial pressure (MAP), plasma renin activity (PRA) and plasma immunoreactive renin (PIR) compared with the control group. Kidney renin content was significantly increased compared with the control group and enlarged renin granules containing heterogenous internum were observed in juxtaglomerular cells after treatment with ES-8891. Treatment with captopril significantly increased PRA and PIR compared with the control day as well as increasing kidney renin content and the number of renin granules with crystalline content in juxtaglomerular cells compared with the control group. These results suggest that ES-8891 inhibits both PRA and renin secretion from the kidney, resulting in an increase in renal renin storage

Kidney renin gene expression after renin inhibition in the marmoset.

1. The effects of renin inhibitor ES-8891 on renin synthesis and its secretion by the kidney were investigated in normotensive sodium-depleted marmosets. We measured plasma renin activity, plasma immunoreactive renin concentration, plasma angiotensin II concentration and kidney renin mRNA content after oral administration of ES-8891 (60 mg day-1 kg-1) for 1 week. 2. The mean blood pressure was significantly decreased (P less than 0.01) on day 7 after oral administration of ES-8891. There was no significant change in heart rate during the administration. 3. Oral administration of ES-8891 for 1 week markedly decreased the plasma renin activity, the plasma immunoreactive renin concentration and the plasma angiotensin II concentration (to 18%, 41% and 24% of the corresponding control values; P less than 0.05 for each, n = 5). 4. The kidney renin mRNA content in ES-8891-treated marmosets was significantly lower than that in normal controls (4.2 +/- 3.5 versus 12.8 +/- 5.5 pg/micrograms of total RNA, means +/- SD, P less than 0.05, n = 5). 5. Oral administration of the renin inhibitor ES-8891 for 1 week not only inhibited plasma renin activity but also decreased renin synthesis and its secretion by the kidney.

The effect of the renin inhibitor ES-1005 on the expression of the kidney renin gene in sodium-depleted marmosets

The effect of the renin inhibitor ES-1005 or captopril on the expression of the kidney renin gene was investigated in sodium-depleted marmosets. We measured the level of kidney renin messenger RNA (mRNA) after continuous administration of ES-1005 (48 mg/kg per day) or captopril (2 mg/kg per day) intraperitoneally, via an osmotic mini-pump, for one week. The level of kidney renin mRNA was measured by densitometric Northern blot analysis using an alpha-32P-labelled human renin cDNA fragment as the hybridization probe. Captopril treatment markedly increased plasma renin activity and the level of kidney renin mRNA by 4.7-fold and 6.3-fold, respectively. ES-1005 treatment completely inhibited plasma renin activity and significantly decreased the level of kidney renin mRNA (46% of the normal control P less than 0.01). However, plasma immunoreactive renin concentration was significantly increased by the treatment with ES-1005 (P less than 0.05). These results suggest that the treatment with the renin inhibitor ES-1005 for one week has a paradoxical effect on kidney renin gene expression and renin release from the kidney in sodium-depleted marmosets.

Sandwich radioimmunoassay of human plasma renin using two monoclonal antibodies.

Plasma immunoreactive renin was measured by sandwich radioimmunoassay, under various physiological and pathological conditions. Enzymatic activities of active renin and trypsin-activatable inactive renin were also measured. There was a significant correlation between plasma immunoreactive renin concentration (IRRC) and total (active plus inactive) renin concentration, as estimated by enzymatic activity. In plasma from normotensive volunteers and hypertensive patients, the IRRC were 279 +/- 37 pg/ml and 268 +/- 29 pg/ml, respectively. After the intravenous injection of furosemide, the plasma IRRC in normotensive volunteers increased significantly. IRRC was significantly higher in plasma from juvenile diabetics than in plasma from age-matched disease-free children. Thus, renin secretion in children with diabetes mellitus is increased.

Increased plasma renin during renin inhibition. Studies with a novel immunoassay.

The response of renin release to the administration of renin inhibitors cannot be studied with conventional enzymatic methods used to measure plasma renin. In the present experiments, a novel multirange enzyme-linked immunosorbent assay for human and primate renin was used to investigate the changes in plasma immunoreactive renin after renin inhibition. A potent and long-acting statine-containing renin inhibitor, CGP 29 287, was injected in conscious marmosets after mild or severe sodium depletion. In mildly sodium-depleted marmosets, CGP 29 287 (0.1 mg/kg i.v.) reduced mean arterial blood pressure and completely inhibited plasma renin activity for up to 30 minutes. This response was associated with a transient increase in plasma immunoreactive renin concentration. After a dose of 1.0 mg/kg i.v., the reduction of mean arterial pressure and the complete inhibition of plasma renin activity persisted for up to 120 minutes. These effects were accompanied by a sustained increase in plasma immunoreactive renin concentration. In severely sodium-depleted marmosets, CGP 29 287 (1.0 mg/kg i.v.) induced a marked fall in systolic blood pressure and complete inhibition of plasma renin activity within 30 minutes of injection. Plasma immunoreactive renin levels increased to 257% of pretreatment values. The converting-enzyme inhibitor enalaprilat (2 mg/kg i.v.) induced a fall in systolic blood pressure of similar magnitude, which was accompanied by an increase in plasma renin activity. Levels of plasma immunoreactive renin increased to 210% of pretreatment values. Hydralazine (0.2 mg/kg i.v.) did not increase plasma renin activity or plasma immunoreactive renin levels despite a comparable hypotensive effect.(ABSTRACT TRUNCATED AT 250 WORDS)