Ronald Kramp

DIFFERENTIAL REGULATION OF ANGIOTENSIN II RECEPTORS DURING RENAL INJURY AND COMPENSATORY HYPERTROPHY IN THE RAT

1. The renin‐angiotensin system may be involved in the compensatory adaptations occurring after the reduction of renal mass and during the consecutive changes leading to chronic renal failure. We therefore investigated the regulation of angiotensin II receptors in two models of renal hypertrophy in the rat: hypertrophy following uninephrectomy (UNx) or subtotal nephrectomy (STNx). The level of angiotensin type 1 (AT1A‐R and AT1B‐R) and type 2 (AT2‐R) receptor mRNA was quantified by competitive reverse transcription‐polymerase chain reaction (RT‐PCR) in specific renal zones and the intrarenal distribution of angiotensin II receptors was analysed by immunohistochemistry.

Measurement of Changes in Glomerular Filtration Rate Induced by Atrial Natriuretic Peptide in the Rat Kidney

This study was undertaken to improve the measurement of glomerular filtration rate (GFR) during the acute diuretic phase induced by atrial natriuretic peptide (ANP), which may indeed alter the renal clearance of inulin (GFRCL) due to dead space error. A technique to measure GFR without urine collections was therefore developed in anaesthetized rats prepared as for micropuncture. To do so, arterial blood was periodically collected and renal venous blood was withdrawn simultaneously from a catheter inserted into the left suprarenal vein to determine the renal extraction coefficient of inulin (CEIN). In addition, renal blood flow (RBF) was continuously measured with an electromagnetic flow transducer fitted around the left renal artery to estimate renal plasma flow (RPF). GFR (GFRCE) was then calculated as the product of RPF and CEIN. To study the effects of ANP on GFR, rats were injected i.v. with 10 μl of saline without (n= 6; vehicle) or with 1 μg ANP (n= 6; ANP) and GFRCE and GFRCL were compared before and after each treatment. They did not differ significantly during baseline measurements in each experimental group and were not modified after vehicle. Similarly, RBF remained constant. In contrast, RBF and GFRCE increased rapidly and simultaneously 90 s after ANP, from 9·07 ± 0·25 to 10·07 ± 0·35 (12%) and from 1·209 ± 0·188 to 1·715 ± 0·190 ml min−1 (42%), respectively (P < 0·05). GFRCL increased to an even greater extent (88%). Moreover, the peak enhancement of GFRCL was delayed and occurred 180 s after ANP. The renal clearance of inulin was thus unduly elevated due to sudden changes in the dead space induced by the diuretic effect of ANP. In conclusion, determination of glomerular filtration rate by the method of renal extraction of inulin provided more reliable results than those achieved using the classical method of renal clearance of inulin. Moreover, it was sufficiently sensitive to detect small and transient changes in GFR induced by the injection of 1 μg ANP.

Changes in renal haemodynamics induced by indomethacin in the rat involve cytochrome P450 arachidonic acid-dependent epoxygenases‡

1. A significant renal vasodilation was observed previously after an acute cyclo‐oxygenase (COX) inhibition induced with indomethacin. Because this effect could be due to COX‐dependent intrarenal metabolization of arachidonic acid through cytochrome P450 (CYP450) pathways, the aim of the present study was to investigate, in vivo, possible interactions between COX and CYP450 mono‐oxygenases.

Differential effects of sulindac on renal hemodynamics and function in the rat

Renal hemodynamics were studied using an electromagnetic perivascular flow sensor in anesthetized rats injected i.v. with vehicle, 5 or 10 mg/kg body weight (b.w.) sulindac. No hemodynamic changes occurred with vehicle (n = 6), but mean arterial pressure was significantly decreased (by 15 mmHg) with sulindac (n = 12). In the 5 mg/kg b.w. sulindac group (n = 7), renal blood flow progressively and significantly increased from 7.88 +/- 0.36 to 8.98 +/- 0.58 ml/min, except during concomitant intrarenal infusion of 3 mg/kg b.w. per h proadifen (n = 7). The pressure limits for efficient and no renal blood flow autoregulation remained unchanged (approx. 100 and 80 mmHg, respectively). In the 10 mg/kg b.w. sulindac group (n = 5), renal blood flow did not change but autoregulatory pressure limits were lowered by 10 mmHg 2 h after treatment (P < 0.025). Also, Na+ retention was marked. Prostanoid excretion in urine was significantly reduced with either dose but basal plasma renin activity was not (about 8 ng/ml per h; n = 15). When plasma renin activity was enhanced after a reduction in renal perfusion pressure (n = 21), it was decreased from 11.5 +/- 1.2 to 7.4 +/- 0.2 ng/ml per h only by 10 mg/kg b.w. sulindac (P < 0.05; n = 6). In conclusion, differential effects of sulindac on renal hemodynamics, Na+ excretion and plasma renin activity were demonstrated. Renal hemodynamic changes could be related in part to the cytochrome P-450 arachidonic acid pathway.

Le facteur auriculaire natriurétique: rétrospective et perspectives

AbstractSince the hypotensive and natriuretic properties of crude cardiac extracts were first demonstrated in 1981 in the rat, the effector molecule has been isolated, purified and synthesized. The hormonal factor is produced by atrial myocytes in mammals and stored as a prohormone. Secretion mainly results from a volemic stress inducing an atrial stretch. Secretion includes a maturation step. A peptide of 28 amino-acids (ANP) is then released into the bloodstream. ANP has a half-life of a few minutes. ANP binds to specific receptors expressed at the target cell surface. B-receptors mediate the biological actions of ANP by an increase in cGMP while C-receptors are involved in clearance of the peptide. The kidney as well as the cardiovascular and endocrine systems are the main target sites for ANP. The renal effects of ANP are expressed by an enhanced diuresis and natriuresis which may result from an increased glomerular filtration rate and/or a reduced tubular reabsorption of salt and water. Renal hemodyn...

AMPLIFICATION BY ATRIAL NATRIURETIC PEPTIDE OF THE HAEMODYNAMIC AND RENAL RESPONSES TO AN ACUTE VOLUMIC STRESS IN THE RAT

1. The purpose of the present study was to test the effects of synthetic atrial natriuretic peptide (ANP) on renal haemodynamics and excretory capacities of salt and water in the rat during an ‘acute volumic stress’, which was induced by brisk disturbances of the circulatory volume.