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Biomedical subjects

H J Kramer

Publications and source records attributed to H J Kramer.

At least 55 records · Page 3Linked to original sources
PubMed1995

Differential influence of arachidonic vs. eicosapentaenoic acid on experimental pulmonary hypertension.

The impact of the 2- and 3-series prostanoid precursors arachidonic acid (AA) and eicosapentaenoic acid (EPA) on experimental pulmonary hypertension was investigated. The model of buffer-perfused rabbit lungs was stimulated by infusion of Escherichia coli hemolysin (HlyA), which is known to provoke sustained thromboxane (Tx)-mediated pulmonary hypertension. Release of di- and trienoic Tx into the recirculating perfusate was quantified by a post-high-performance liquid chromatography enzyme-linked immunosorbent assay technique. HlyA at 0.08 hemolytic unit/ml caused a sustained rise in pulmonary arterial pressure (PAP; maximum increase 14 +/- 2 mmHg) accompanied by progressive TxB2 liberation (maximum perfusate concn 33 +/- 4 pg/ml, baseline < 2 pg/ml). Between 5 and 30 nM, AA provoked a transient monophasic rise in PAP (maximum pressor response 1.5-15 mmHg) and concomitant TxB2 release (peak concn 2-30 pg/ml). Simultaneous administration of HlyA and AA exhibited additive effects with regard to mediator release and pressor responses. EPA at 200-2,000 nM caused a transient rise in PAP similar to that provoked by 5-30 nM AA (maximum pressor response 3-18 mmHg). This was accompanied by liberation of TxB2 (peak concn 16 +/- 5 and 28 +/- 4 pg/ml after 1,000 and 2,000 nM EPA) and TxB3 (peak concn 9 +/- 4 and 30 +/- 3 pg/ml). Combined application of HlyA and EPA resulted in approximate addition of the TxB2 release reaction to each single compound, and TxB3 liberation more than doubled (maximum concn 59 +/- 12 pg/ml). The pressor responses to HlyA-EPA (200-2,000 nM) did not, however, surpass those to HlyA-AA (5-30 nM).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Exercise increases endothelin-1 plasma concentrations in patients with coronary artery disease: modulatory role of LDL cholesterol and of pentaerithrityltetranitrate.

Previous studies suggest that ET-1 plays a role in induction of coronary artery disease (CAD). It was shown that secretion of endothelin-1 (ET-1) by the vascular endothelium is enhanced in atherosclerotic alterations and may be antagonized by EDRF. The objective of the present study was to investigate the effects of ergometric exercise on plasma ET-1 concentrations, and the potential modulatory role of LDL cholesterol, and the effects of an orally administered nitrate, PETN, in patients with CAD. Ten men with CAD and 10 healthy men underwent bicycle ergometry according to the WHO-standards. Venous blood samples for determination of ET-1 concentrations were drawn directly before and 5 min after ergometric exercise. Patients were randomized and treated for 72 h in a crossover design either with placebo or pentaerithrityltetranitrate (PETN). After 72 h the identical ergometric protocol was repeated. Basal plasma levels of ET-1 were 6.1 +/- 0.7 pg/ml (patients) and 5.5 +/- 0.6 pg/ml (controls) (n.s.). After ergometric exercise ET-1 plasma concentrations rose significantly (7.3 +/- 0.9 pg/ml; p < 0.05) in the patient group under placebo treatment, whereas they remained constant (5.5 +/- 0.7 pg/ml) with PETN treatment. ET-1 levels remained unaffected by ergometric exercise in healthy controls. Mean LDL cholesterol plasma levels in patients with CAD were 156 +/- 8 mg% and 152 +/- 7 mg% in healthy controls. In the patient group there was a significant (p < 0.002) positive correlation between the exercise-induced increase in ET-1 and the LDL cholesterol plasma concentrations (r = 0.85). Blood pressure and heart rate were not modified by PETN treatment. In patients with CAD bicycle ergometry induced an increase in ET-1 plasma concentrations. The positive correlation with the LDL cholesterol plasma levels indicates that LDL cholesterol is involved in regulation of ET-1 secretion in vivo. PETN therapy completely abolished the exercise-induced increase in ET-1 plasma levels. This may result from local hemodynamic effects of the nitrate; hypothetically a nitrate-induced rise in the local NO concentrations can be considered. The clinical implications of these findings remain elusive. However, the findings of the present study are in accordance with the beneficial clinical effects of nitrates in patients with CAD.

Cholesterol, LDL↗
PubMed1994

The effect of kinin and prostaglandin inhibitors on the renal response to angiotensin-converting enzyme inhibition: a micropuncture study in the dog.

It has been suggested that angiotensin-converting enzyme (ACE) inhibition is accompanied by enhanced bradykinin and prostaglandin activities, which may contribute to the renal haemodynamic actions of ACE inhibitors. Therefore we investigated renal function by clearance and micropuncture techniques in dogs maintained either on normal or low-salt diet before and after ACE inhibition with an i.v. bolus of 0.1 mg/kg ramiprilat followed by an infusion of 5 micrograms kg-1 min-1. Subgroups each comprising six dogs were also treated with either HOE-140, a bradykinin B2 receptor antagonist, or the cyclooxygenase inhibitor indomethacin. In general, renal effects of ramiprilat were more pronounced in dogs fed on low salt than in those on normal diet. In dogs on low salt, the mean arterial pressure decreased by 20% 20 min after ramiprilat application, whereas the total renal blood flow rose by 71% from 4.71 to 8.06 ml min-1 g kidney weight-1 and the glomerular filtration rate (GFR) by 28% from 0.74 to 0.95 ml min-1 g-1. Single-nephron glomerular blood flow and single-nephron GFR rose by 55% and 23% respectively. The total and the single-nephron filtration fraction decreased by 25% and 23% respectively. There were no substantial changes in glomerular and peritubular capillary and tubular pressures, but a significant increase in the ultrafiltration coefficient, Kf, by 103% from 3.55 nl/mmHg to 7.19 nl/mmHg (26.7-54.0 nl/kPa) was observed. Afferent and efferent arteriolar resistances decreased in parallel by 55% and 47%.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1994

Cyclosporine A enhances total cell calcium independent of Na-K-ATPase in vascular smooth muscle cells.

The effect of cyclosporine A in enhancing vasconstrictor-induced calcium (Ca2+) mobilization in vascular smooth muscle cells may contribute to important side effects in cyclosporine therapy such as hypertension and nephrotoxicity. As we have previously shown, cyclosporine A stimulates transmembrane Ca2+ influx. Since Ca2+ efflux was not affected by cyclosporine A, we concluded that cyclosporine augments angiotensin II induced Ca2+ mobilization in vascular smooth muscle cells by an increased amount of Ca2+ in angiotensin II sensitive intracellular Ca2+ stores. The present study was therefore designed to examine the effect of cyclosporine A on cellular calcium content and on membrane calcium transport mechanisms. An important mechanism of Ca2+ extrusion from the cell is the Na-Ca exchanger. Its activity is closely related with that of the Na-K-ATPase. By increasing cellular sodium concentration the blockade of Na-K-ATPase would in turn activate cellular calcium uptake bx the Na-Ca exchanger. Therefore, we hypothesized that cyclosporine A might exert its effects in the same manner as a circulating Na-K-ATPase inhibitor. Total cell calcium was measured by atomic absorption and activity of Na-K-ATPase was estimated by an assay measuring phosphate production. Preincubation of the cells with cyclosporine (10 micrograms/ml) for 15 min increased total cell calcium from 31.4 +/- 5.0 to 46.5 +/- 5.3 nmol/mg protein (P < 0.05). Activity of Na-K-ATPase was not affected by cyclosporine A (3.9 +/- 0.2 vs. 4.3 +/- 0.2 mumol Pi h-1 mg-1 protein). Therefore, cyclosporine A induced Ca2+ influx is not mediated by an inhibition of the Na-K-ATPase.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Atrial natriuretic peptide inhibits cyclosporin A-induced endothelin production and calcium accumulation in rat vascular smooth muscle cells.

1. As we have previously shown, cyclosporin A enhances the vasoconstrictor-induced rise in intracellular free calcium in vascular smooth muscle cells. This effect may contribute to important side-effects in cyclosporin therapy, such as hypertension and nephrotoxicity. Atrial natriuretic peptide has been shown to inhibit this effect as well as the cyclosporin-stimulated transmembrane calcium influx in smooth muscle cells. 2. The present study, therefore, was designed to examine the effect of cyclosporin and atrial natriuretic peptide on total cellular calcium content in the rat. Furthermore, since cyclosporin was recently shown to induce endothelin production in smooth muscle cells, we investigated the effect of atrial natriuretic peptide on this potentially adverse cellular effect of cyclosporin therapy. 3. Total cell calcium was measured by atomic absorption, and cellular endothelin production was estimated by radioimmunoassay. 4. Preincubation of the cells with cyclosporin (10 micrograms/ml) for 30 min increased total cell calcium from 2.6 +/- 0.5 to 6.9 +/- 0.3 nmol/mg of protein (P < 0.01). Within 24 h endothelin production was significantly enhanced in the presence of cyclosporin (52.2 +/- 2.5 versus 65.9 +/- 2.7 fmol/mg of protein, P < 0.05). Therefore, the cyclosporin-induced rise in total cell calcium in smooth muscle cells is associated with enhanced production of endothelin. Thus, it is tempting to speculate that the cyclosporin-induced changes in calcium kinetics may be mediated by endothelin. 5. In the presence of atrial natriuretic peptide (10(-8) mol/l), the cyclosporin-induced rise in total cell calcium was significantly reduced (6.9 +/- 0.3 versus 5.1 +/- 0.2 nmol/mg of protein, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Metoclopramide does not affect renal function and atrial natriuretic peptide release in response to acute saline loading in conscious rats.

It was previously shown in man that metoclopramide (MCP), a dopamine (DA)-2 receptor blocker, attenuates the natriuresis of water immersion. In the present study, we therefore investigated the effects of MCP on renal function and atrial natriuretic peptide (ANP) release in conscious rats. Under basal conditions MCP did not affect glomerular filtration rate (GFR) (7.4 +/- 1.7 ml/min/kg without and 7.8 +/- 0.6 ml/min/kg with MCP), urinary fractional excretion of Na (FENa) (0.3 +/- 0.1% without and 0.3 +/- 0.1% with MCP) and K (FEK) (20.6 +/- 1.4% without and 28.0 +/- 6.2% with MCP) or plasma ANP (37 +/- 5 pmol/l without and 31 +/- 6 pmol/l with MCP). During acute saline loading equal to a 10% rise in body weight, which significantly (p < 0.05) increased GFR, MCP again had no effects on GFR (8.8 +/- 1.8 ml/min/kg with vs. 9.7 +/- 2.5 ml/min/kg without MCP), FENa (24.5 +/- 6.9% with vs. 20.4 +/- 5.1% without MCP), FEK (52.5 +/- 6.9% with vs. 52.5 +/- 9.5% without MCP) and plasma ANP (89 +/- 8 pmol/l with vs. 91 +/- 9 pmol/l without MCP). These results indicate that DA does not modulate renal function or ANP release via DA-2 receptors under basal conditions nor in response to acute saline loading in conscious rats.

Animals↗
PubMed1994

Lisinopril versus slow release nifedipine in patients with essential hypertension: a multicentre study.

The present study was performed to investigate the efficacy and safety of the angiotensin converting enzyme (ACE) inhibitor lisinopril compared with those of the calcium channel blocker nifedipine in 293 patients with mild to moderate essential hypertension (supine diastolic blood pressure (DBP) 95-115 mmHg) in a multicentre, randomised, double-blind parallel group study after a two week single-blind placebo run-in period. Thus, the haemodynamic effects as well as side-effects during antihypertensive treatment were examined in 146 patients receiving lisinopril (20 mg once daily) and in 147 patients receiving slow release nifedipine (20 mg twice daily) who entered the six weeks' treatment period. From the analysis of efficacy one patient from the lisinopril and two patients from the nifedipine groups were excluded because their supine DBP after run-in was < 95 mmHg. Adverse reactions, mostly transient during the initial treatment period, and withdrawals occurred in six (4.1%) and three (2.1%) patients of the lisinopril group and in 12 (8.2%; NS) and three (2.0%) patients of the nifedipine group, respectively. After the six weeks' treatment period the lisinopril group showed 19 nonresponders (supine DBP > or = 95 mmHg) of the remaining 142 patients and the nifedipine group revealed 20 nonresponders of the remaining 142 patients. Initial supine and standing heart rates were similar in both groups. Supine heart rate fell significantly in the lisinopril group, whereas standing heart rate in this group and supine and standing heart rates in the nifedipine group did not change significantly with treatment. Thus, lisinopril proved to be as effective and safe as nifedipine with responder rates of 86.6% and 85.9%, respectively.

Blood Cell Count↗
PubMed1994

[Use of natriuretic peptides in clinical practice].

Due to its physiological and pharmacological action ANF could be an ideal diuretic and vasorelaxation product in the treatment of oedema and essential hypertension. Experimental and clinical investigations in oedematous conditions revealed a very slight diuretic and natriuretic effect of ANF, as compared with healthy subjects. This is due to the reduced renal perfusion pressure, the increased RAAS activity, enzymatic degradation of ANF by endopeptidase and also its inactivation via C-receptors. Moreover the use of ANF is very limited due to its short half-life and peptide structure. In recent years therefore new possibilities are sought how to influence the metabolism of endogenous ANF and thus increase its activity. Neutral endopeptidase inhibitors (NEP) inhibit ANF degradation, increase thus its plasma level and in cardiac weakntlakess have a marked diuretic and natriuretic effect. The administration of NEP inhibitors in patients with essential hypertension did not reveal so far an adequate effect on blood pressure. Inhibitors of C-receptors potentiate also the effect of endogenous ANF. In experiments they enhance Na excretion and lead to a drop of blood pressure. Recently another natriuretic peptide was detected--urodilatine. In experimental and clinical studies in cardiac failure urodilatine administration leads to an increase of diuresis and natriuresis greater than after ANF. Haemodynamic effects after urodilatine are also greater than after ANF whereby urodilatine does not cause reflex tachycardia and is resistant to peptidase degradation. Its therapeutic administration is a new perspective in the treatment of oedematous conditions and essential hypertension.

Atrial Natriuretic Factor↗
PubMed1993

Cellular signaling by cyclosporine A in contractile cells: interactions with atrial natriuretic peptide.

Immunosuppressive therapy with cyclosporine A (CyA) may be associated with severe side effects such as nephrotoxicity and arterial hypertension. The partial reversibility of these effects suggests that they are at least in part functional. The present study examined the effects of CyA on cellular signaling in vascular smooth muscle cells and in glomerular mesangial cells and the interactions with the endogenous vasodilator atrial natriuretic peptide (ANP). Intracellular free calcium concentrations ([Ca2+]i) were measured using Fura-2. 45Ca2+ was used to measure Ca2+ efflux and cellular Ca2+ influx. In the presence of cyclosporine (10 micrograms/ml), the Ca(2+)-mobilizing effects of angiotensin II (10(-8)M) in smooth muscle cells and of arginine vasopressin (AVP) in mesangial cells were significantly enhanced. CyA significantly stimulated cellular Ca2+ uptake in both cell types. ANP blocked the Ca2+ mobilization by angiotensin II and AVP and also completely inhibited the potentiating effect of CyA on angiotensin II- and AVP-induced Ca2+ mobilization. ANP also completely blocked the CyA-stimulated Ca2+ uptake. These findings suggest that CyA stimulates transmembrane Ca2+ influx, thereby increasing vasopressor-sensitive intracellular Ca2+ stores and augmenting vasopressor-induced Ca2+ mobilization. This cellular effect of CyA in vitro was markedly diminished by ANP. The effects of CyA on intracellular signaling may directly enhance the contractile response of smooth muscle and the glomerular mesangium to vasopressor stimuli and may also contribute to other disturbances of cell metabolism associated with CyA.

Angiotensin II↗
PubMed1993

Rat renal, aortic and pulmonary endothelin-I receptors: effects of changes in sodium and water intake.

1. In the present study we investigated, first, the effects of high Na+ intake and, second, the effects of water deprivation on plasma endothelin-1 concentration and urinary endothelin-1 excretion and on endothelin receptors in membranes of renal glomeruli and papillae and of aortic smooth muscle and lung tissue from 32 female Sprague-Dawley rats. 2. After 5 weeks of high Na+ intake (n = 8) urinary Na+ excretion was 10.5 +/- 1.3 compared with 1.6 +/- 0.2 mmol/24 h in controls. Body weight, plasma osmolarity, plasma endothelin-1 concentration (23 +/- 6 versus 28 +/- 3 fmol/ml) and urinary endothelin-1 excretion (6.1 +/- 1.3 versus 4.7 +/- 0.3 pmol/24 h) remained unchanged. 3. The characteristics of endothelin-1 receptors in glomeruli, papillae, aortic smooth muscle and lung tissue from salt-loaded rats were not different from those of controls. 4. After 48 h water deprivation (n = 8) body weight had decreased, whereas packed cell volume and plasma and urine osmolarities had increased compared with controls (n = 8) (P < 0.05). Plasma endothelin-1 concentration (40 +/- 6 versus 21 +/- 2 fmol/ml) was higher (P < 0.01) and urinary endothelin-1 excretion (1.0 +/- 0.2 versus 2.8 +/- 0.3 pmol/24 h) was lower than in controls (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Characteristics of endothelin receptors and intracellular signalling in porcine inner medullary collecting duct cells.

In porcine kidneys we investigated the characteristics of endothelin (ET) receptors that are present in papillary tissue but not in glomeruli. Therefore, porcine inner medullary collecting duct (IMCD) cells were separated by Percoll density gradient centrifugation after enzymatic and hypotonic treatment of minced papillary tissue. Studies were performed in fresh cell suspensions and in cells in primary culture. Changes in cytosolic free Ca2+ concentration [Ca2+]i were measured by the use of fura-2. Optimum binding of ET-1 was obtained by incubation for 120 min at 37 degrees C, pH 7.0 when maximal protein content was 40 micrograms. Analysis with the LIGAND program showed an average number of binding sites (Bmax) of 26.0 +/- 30.5 fmol/mg protein and dissociation constant (Kd) of 90.5 +/- 28.6 pmol/L for ET-1 and Bmax of 246.9 fmol/mg protein and Kd of 162.5 pmol/L for ET-3. ET-1, 10(-9) to 10(-6) mol/L, dose dependently raised [Ca2+]i four to tenfold, respectively, from a mean basal level of 41 nmol/L. This rise was significantly attenuated by TMB-8 and by verapamil. Preincubation with Ni2+ almost completely prevented the increment in [Ca2+]i. ET-1 slightly suppressed basal and significantly attenuated arginine vasopressin (AVP)-induced cyclic adenosine monophosphate (cAMP) synthesis. Thus, porcine IMCD cells possess a single class of super high affinity ETB receptors (ETB1). ET-1 raises [Ca2+]i through release from intracellular stores, activation of L-type calcium channels and, probably to a larger extent, through stimulation of other channels, eg, T-type calcium channels or unselective cation channels.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Cellular mechanisms of action of a ouabain-like factor in vascular smooth-muscle cells.

Ouabain-like factor (OLF) has been implicated to play an important role in certain forms of hypertension. We isolated OLF from the urine of salt-loaded healthy subjects by stepwise chromatographic procedures. The post-salt fraction (F IV) eluted from Sephadex G-25 was rechromatographed on Sephadex G-10. A late small-molecular-weight fraction F8 inhibited Na-K-ATPase in vitro (OLF activity). The effects of OLF on intracellular Ca2+ concentrations ([Ca2+]i) and pH (pHi) were examined in cultures of vascular smooth-muscle cells using the fluorescent probes fura-2 and 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF), respectively. Preincubation with OLF increased basal [Ca2+]i from 87 +/- 6 to 160 +/- 8 nM (p < 0.001) and enhanced arginine vasopressin-stimulated maximal [Ca2+]i (418 +/- 11 vs. 523 +/- 14 nM, p < 0.01). This effect was similar to that of ouabain. OLF also induced a rapid transient increase of [Ca2+]i (82 +/- 9 vs. 253 +/- 23 nM, p < 0.01); [Ca2+]i returned to levels slightly above baseline within approximately 4 min. OLF-stimulated [Ca2+]i was attenuated by verapamil (126 +/- 5 nM, p < 0.01) and was also reduced in Ca(2+)-free medium (104 +/- 9 nM, p < 0.01). As opposed to OLF, ouabain did not exhibit this fast transient effect on [Ca2+]i. Amiloride (10(-3) M) blocked the sustained effect of OLF on [Ca2+]i (77 +/- 11 vs. 86 +/- 12 nM, NS). OLF induced an increase of pHi from 7.09 +/- 0.03 to 7.28 +/- 0.04 (p < 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Atrial natriuretic peptide blunts the cellular effects of cyclosporine in smooth muscle.

The effect of cyclosporine A to enhance vasoconstrictor-induced calcium (Ca2+) mobilization in vascular smooth muscle cells may contribute to important side effects in cyclosporine therapy such as hypertension and nephrotoxicity. On the other hand, atrial natriuretic peptide (ANP) is known to diminish vasoconstrictor-stimulated Ca2+ mobilization. The present study, therefore, examined the interaction of cyclosporine and ANP on Ca2+ kinetics in cultured rat vascular smooth muscle cells. Intracellular free calcium concentrations ([Ca2+]i) were measured using fura-2. 45Ca2+ was used to estimate Ca2+ efflux and cellular Ca2+ influx. Preincubation of the cells with cyclosporine (10 micrograms/ml) for 12 minutes lowered basal [Ca2+]i from 48 +/- 4 to 28 +/- 3 nM (p < 0.01). However, in the presence of cyclosporine, the angiotensin II (10(-8) M)-stimulated rise of [Ca2+]i was increased from 296 +/- 22 to 460 +/- 47 nM (p < 0.001). ANP (5 x 10(-9) M) blocked the Ca2+ mobilization by angiotensin II (71 +/- 7 versus 69 +/- 7 nM, NS) and also completely inhibited the effect of angiotensin II in the presence of cyclosporine (77 +/- 5 versus 78 +/- 5 nM, NS). Basal efflux as well as angiotensin II-stimulated 45Ca2+ efflux were not altered by preincubation with cyclosporine, indicating that the effect of cyclosporine on [Ca2+]i was not due to an inhibition of 45Ca2+ efflux.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Effects of thromboxane A2 receptor blockade on oliguric ischemic acute renal failure in conscious rats.

To investigate the potential pathogenetic and therapeutic roles of thromboxane A2 (TXA2) and its receptor blockade, respectively, in the early phase of ischemic acute renal failure (ARF), renal function, TXB2 excretion, and the effects of the specific TXA2 receptor antagonist sulotroban (SU) in a model of unilateral renal artery occlusion in conscious female Sprague-Dawley rats were studied. Occlusion of the left renal artery for 1 h in untreated (i.e., vehicle-treated) rats (N = 8) resulted in oliguric ARF. In SU-treated rats (N = 8), the drug was given as an i.v. bolus of 5 mg/kg body wt, followed by a continuous infusion of 0.5 mg/min.kg body wt from 1 h before and during ischemia and for 6 h after reflow. After 1 h of ischemia, urine volume of left ischemic kidneys from untreated rats had decreased from 13.2 +/- 2.8 to 1.0 +/- 0.3 and 0.5 +/- 0.2 microL/min.100 g at 2 and 6 h of reflow, respectively, and GFR had decreased from 0.32 +/- 0.04 mL/min.100 g body wt to undetectable values. At 6 h of reflow, medullary Na-K-ATPase was slightly (P < 0.05) reduced in left ischemic kidneys, whereas medullary and papillary enzyme activities were compensatorily increased (P < 0.01) in right intact kidneys. The ADP/O ratio of cortical mitochondria was 41% (P < 0.05) and ATP synthesis was 77% (P < 0.01) lower than in right intact kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1992

Selective downregulation of rat renal clearance receptors for atrial natriuretic peptide by chronic high-salt intake: study on isolated membranes using 125I-labelled c-atrial natriuretic peptide-(4-23).

1. 125I-labelled c-atrial natriuretic peptide-(4-23) was used as radioligand for the direct quantification of atrial natriuretic peptide clearance receptors, and 125I-labelled rat atrial natriuretic peptide-(1-28) was used for the determination of total and biologically active atrial natriuretic peptide receptors, in renal glomerular and papillary membrane preparations of chronically salt-loaded and control rats. 2. The membrane preparation technique included acid-washing (pH 5), and receptor binding was assessed by saturation studies at 4 degrees C for 3 h. Chronic salt loading revealed a 35% decrease in clearance receptor number in the glomerular membrane and a 42% decrease in the papillary membranes. The absolute decrease in clearance receptor number was almost identical with the observed reduction in absolute number of total atrial natriuretic peptide receptors. Biologically active receptors were not affected by chronic salt loading. 3. Selective downregulation of clearance receptors for atrial natriuretic peptide may reflect an important role for the rat renal atrial natriuretic peptide system in long-term fluid and electrolyte regulation.

Animals↗