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Biomedical subjects

H J Kramer

Publications and source records attributed to H J Kramer.

At least 19 recordsLinked to original sources
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↗
PubMed1992

Intranasal application of atrial natriuretic peptide and 1-deamino-d-arginine vasopressin in healthy volunteers. Hemodynamic, hormonal, and renal excretory effects.

In the present study we investigated the effects of an intranasal administration of 25 micrograms alpha-human atrial natriuretic peptide (alpha-hANP) dissolved in 0.2 mL 0.9% saline on renal excretory function, blood pressure (BP), heart rate (HR), and also its interaction with the renal effects of 20 micrograms deamino-d-arginine vasopressin (d-DAVP) in 10 healthy volunteers. After two 30-min control periods plasma concentrations of ANP and cGMP rose significantly from 14.8 +/- 1.8 pmol/L and 5.9 +/- 0.3 pmol/mL to 23.3 +/- 2.3 pmol/L and 6.6 +/- 0.4 pmol/mL (P less than .05), respectively within 30 min after ANP administration. The levels returned to basal values after 60 min. Urinary cGMP excretion initially rose from 17.9 +/- 3.6 to 46.8 +/- 3.7 pmol/30 min and then returned to control values, whereas plasma renin activity and plasma aldosterone concentration decreased significantly after 30 and 60 min (P less than .05). Systolic and diastolic BP declined slightly by 8% and 7%, respectively, while HR remained unaltered. Urine flow rate and sodium excretion increased by 321% and 190%, respectively (P less than .05). These changes were also significant when data were compared with a time-matched placebo study performed on the preceding day with intranasal administration of 0.2 mL 0.9% saline alone. After 48 h the protocol was repeated but 20 micrograms d-DAVP was administered intranasally 120 min before an intranasal application of 25 micrograms alpha-hANP. Within 120 min d-DAVP had reduced urine flow by approximately 50% (P less than .05), while sodium excretion remained unaltered.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intranasal↗
PubMed1992

Role of calcium in the progression of renal disease: experimental evidence.

Intracellular calcium mediates a wide array of cell functions in mesenchymal as well as in epithelial and endothelial cells. These comprise regulation of vascular tone, cell proliferation and synthesis of prostanoids and cytokines. Therefore, it is not surprising that a substantial body of evidence has emerged to suggest a crucial role of calcium in the initiation and perpetuation of renal disease. Increased deposition of calcium was found in the renal cortex of rats with remnant kidney and in kidney tissue of patients with end-stage renal failure. Calcium plays an important role in altered intrarenal and glomerular hemodynamics with increased glomerular wall tension as well as in cellular proliferation and in recurrent ischemic events leading to glomerulosclerosis and interstitial fibrosis. Besides hemodynamic mechanisms, additional calcium-dependent mechanisms must be considered for glomerular hypertrophy and/or mesangial proliferation to develop, namely the role of growth factors, prostanoids and cytokines. Their signals include receptor-regulated production of inositol-trisphosphate and diacylglycerol and the consecutive stimulation of protein kinase C and the Na/H-antiport. Full activation of this antiport, which raises intracellular pH and thereby stimulates protooncogenes, again requires the presence of calcium. Recurrent focal glomerular ischemia may result in cellular and mitochondrial calcium overload that may interfere with cellular energy metabolism. Calcium also activates proteinases and the production of oxidants to enhance neutrophil-mediated cell injury. These deleterious effects of calcium may initiate and perpetuate the progression of renal disease and eventually lead to end-stage renal failure.

Animals↗
PubMed1991

Effects of atrial natriuretic peptide on systemic and renal hemodynamics and renal excretory function in patients with chronic renal failure.

We examined the effects of 60 min alpha-hANP infusion (24 ng/min/kg) on glomerular filtration rate (GFR), renal blood flow (RBF), cardiac index (CI) and blood pressure (BP) in 8 patients with chronic renal failure (CRF) with GFR ranging from 18 to 80 ml/min/1.73 m2 and in 8 control (C) subjects with normal renal function. Basal plasma levels of ANP and cGMP were elevated in CRF (ANP: 60.6 +/- 9.1 vs 13.6 +/- 1.9 pmol/l, p less than 0.05; cGMP: 14.3 +/- 2.9 vs 6.6 +/- 1.1 pmol/ml, p less than 0.05). During ANP infusion, peak levels of cGMP were higher in CRF than in C (27.5 +/- 3.2 vs. 17.3 +/- 1.3 pmol/ml, p less than 0.05). During ANP infusion, GFR increased in CRF by 70.7 +/- 4.2% from 34.5 +/- 6.8 to 57.4 +/- 9.9 ml/min/1.73 m2 (p less than 0.001) as compared to 16.2 +/- 1.4% in C (p less than 0.001 vs CRF). RBF increased in CRF by 43.6 +/- 6.4% and in C by 3.1 +/- 1.2% (p less than 0.01). Basal urinary sodium excretion (UNaV) was slightly lower in CRF than in C but rose to the same level in both groups during ANP infusion. In CRF, as opposed to C, UNaV remained elevated above baseline after the end of the infusion. The effect of ANP on fractional sodium excretion (FENa), however, was more pronounced in C.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Endogenous natriuretic and ouabain-like factors. Their roles in body fluid volume and blood pressure regulation.

An endogenous ouabain-like sodium pump inhibitor was demonstrated originally in serum or plasma of acutely extracellular fluid volume (ECFV) expanded animals and humans. Since then numerous studies have confirmed the presence of ouabain-like factor(s) (OLF) in blood, urine, cerebrospinal fluid, and various tissues including the heart and hypothalamus. Some of these OLFs represent well-known endogenous compounds, eg, free unsaturated fatty acids, which in vitro exhibit inhibition of transepithelial sodium transport, direct inhibition of the Na-K-ATPase enzyme, displacement of 3H-ouabain from its membrane receptor, and crossreaction with a digoxin antibody. Small molecular weight (MW) OLFs of yet unknown peptidic or nonpeptidic nature, which may be of hypothalamic origin, were also detected in various animal models of hypertension and in hypertensive patients. They may play a pathophysiological role especially in salt- and volume-dependent forms of hypertension. Our results show that OLFs increase basal and vasopressin-stimulated intracellular Ca2+ release in rat vascular smooth muscle cells in culture and in human platelets similar to the newly discovered endothelin. In addition, a natriuretic factor (natriuretic hormone) was detected by bioassay in plasma and urine, whose activity changes in parallel with sodium intake. We found that this natriuretic factor is associated with small peptides with a MW of less than 1,000. It is, however, unlikely that the two biological properties, ie, the ouabain-like and natriuretic activities, reside in a single compound. A number of circulating OLFs is certainly not identical with a humoral natriuretic factor. Nevertheless, there is increasing evidence for multiple interactions between OLF and the atrial natriuretic peptide (ANP).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Atrial natriuretic peptide in patients with essential hypertension. Hemodynamic, renal, and hormonal responses.

In six patients with essential hypertension (EH) and in six healthy volunteers (C) the effects of a 60-min intravenous (iv) infusion of human atrial natriuretic peptide (alpha-hANP) (24 ng/min/kg) on systemic and renal hemodynamics and renal excretory function were evaluated. Basal plasma ANP concentrations in patients with EH were higher (P less than .05) than in C (30.9 +/- 4.5 v14.0 +/- 1.7 pmol/L). Maximal effects of alpha-hANP infusion occurred after 30 to 60 min. Blood pressure (BP) declined from 154 +/- 5/109 +/- 4 to 139 +/- 7/94 +/- 4 in EH and from 117 +/- 1/72 +/- 2 to 106 +/- 1/65 +/- 3 mm Hg in C (P less than .05). Cardiac output (CO) increased transiently from 6.1 +/- 0.3 to 6.5 +/- 0.4 L/min in EH and from 6.8 +/- 0.3 to 7.2 +/- 0.5 L/min in C, whereas heart rate (HR) remained constant both in patients with EH and in C (69 +/- 3 to 72 +/- 5 and 60 +/- 3 to 63 +/- 3/min). The increases in urine flow and in urinary sodium excretion from 3.6 +/- 0.2 to 16.0 +/- 2.0 mL/min and from 230 +/- 33 to 1004 +/- 137 mumol/min, respectively, in EH were more pronounced than in C (from 3.9 +/- 1.0 to 8.4 +/- 0.8 mL/min and from 211 +/- 37 to 451 +/- 84 mumol/min); (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

[Effects of the angiotensin converting enzyme inhibitor ramipril on calcium (Ca2+) kinetics in smooth muscle cells].

In order to investigate renin- and angiotensin-independent mechanisms of the angiotensin converting enzyme (ACE) inhibitor ramipril we examined the effects of ramiprilat on calcium mobilization in cultured vascular smooth muscle cells. Ramiprilat (10(-7) M) induced a slow increase of basal [Ca2+]i from 52 +/- 7 nM to 162 +/- 12 nM (p less than .001). This increase of basal [Ca2+]i was associated with contraction of vascular smooth muscle cells as assessed by microscopy in vitro. While ramiprilat itself induced an increase of basal [Ca2+]i, the Ca(2+)-mobilizing effect of angiotensin II (AII) was blunted in the presence of the ACE inhibitor (659 +/- 38 nM vs 360 +/- 45 nM, p less than .001). The calcium channel blocker verapamil did not affect the stimulatory effect of ramiprilat on basal [Ca2+]i. The intracellular Ca2+ antagonist TMB 8 attenuated the ramiprilat-induced increase of basal [Ca2+]i (162 +/- 12 nM vs 101 +/- 14 nM, p less than .05). In the present study, the effect of ramiprilat on [Ca2+]i was not blocked by inhibition of prostaglandin synthesis by meclofenamate (10(-5) M); however, this finding does not rule out in vivo effects of ramiprilat-stimulated prostaglandins. These results suggest that ramipril affects Ca2+ kinetics in vascular smooth muscle cells. Ramiprilat-induced contraction of cultured smooth muscle cells may not be relevant in vivo, but the increase of basal [Ca2+]i by ramiprilat may reflect a "reset" of the cellular Ca(2+)-mobilizing mechanism or a depletion of cellular Ca2+ stores and may thus explain the attenuation of the Ca(2+)-mobilizing effect of AII. This mechanism may result in a decrease of vasopressor-dependent vascular tone in vivo and may contribute to the vasodilatory effect of ramipril.

Angiotensin II↗
PubMed1990

Kinin- and non-kinin-mediated interactions of converting enzyme inhibitors with vasoactive hormones.

The antihypertensive effect of inhibitors of the angiotensin I-converting enzyme (ACE = kininase II) results from their vasodilatory and natriuretic effects as well as their effect on baroreceptor function. In addition to the inhibition of systemic and local angiotensin II formation, other local hormonal systems may also be involved in this effect at multiple target sites. Thus, potentiation of the vasodilator and natriuretic kinin system following inhibition of kininase II is thought to contribute to the persistent hypotensive effect of ACE inhibitors despite normalization of circulating ACE activity. Although increased plasma bradykinin levels cannot be detected, we found that the enhanced kinin-dependent local vascular prostacyclin production can be blunted in vitro by aprotinin, a kallikrein inhibitor. ACE inhibition may affect the atrial natriuretic peptide (ANP) system as the renin-angiotensin system and ANP appear to play antagonistic roles at the peripheral and central nervous system levels. Inhibition of kallikrein or of kininase II were both shown to modulate the natriuretic and vasorelaxant effects of ANP. In hypertensive subjects, we found that ACE inhibition with blood pressure normalization reduces basal and stimulated plasma ANP and blunts the renal sodium excretion in response to saline loading. In contrast, we did not observe effects of acute ACE inhibition in healthy sodium-depleted volunteers on plasma vasopressin under basal conditions or in response to passive tilt. Finally, we investigated the interaction of ACE inhibition with substance P, a powerful endogenous diuretic and natriuretic peptide that may have a transmitter function in the baroreceptor reflex arch.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1979

Effects of aprotinin on renal function and urinary prostaglandin excretion in conscious rats after acute salt loading.

1. Aprotinin, a potent kallikrein inhibitor, was given to conscious rats with and without expansion of the extracellular fluid volume with isotonic saline. 2. In non-expanded rats aprotinin had no effect on arterial pressure, glomerular filtration rate (GFR), hippuran clearance, urinary flow rate, absolute sodium and potassium excretion or free-water clearance. 3. In volume-expanded rats aprotinin significantly reduced GFR, hippuran clearance, urine volume (V) UNaV, UKV and Cwater/GFR without effect on systemic arterial pressure. 4. Urinary immunoreactive prostaglandin E2 excretion significantly increased during the expansion phase but returned to below the control range during stable extracellular fluid volume expansion. 5. Aprotinin significantly suppressed urinary immunoreactive prostaglandin E2 excretion in non-expanded rats and in volume-expand rats during the expansion phase, but not during stable expansion. 6. The results suggest that the kallikrein-kinin system may contribute to changes in renal function during extracellular volume expansion. This action may not necessarily be associated with changes in renal prostaglandin E2 activity.

Animals↗
PubMed1978

Comparative evaluation of metrizamide and meglumine ioxithalamate in angiography of the vessels of the head and neck.

Metrizamide, a non-ionic contrast medium of low osmolality was compared with meglumine ioxithalamate, the ionic angiographic contrast medium currently in use in our department in a double-blind study. Criteria upon which the comparison was based were: 1) the pain reaction of the patient upon intra-arterial contrast injection, 2) bradycardial reactions upon common carotid injection and 3) the quality of the contrast image. Metrizamide induced significantly less painful sensations than meglumine ioxithalamate in those vessels in which injections of contrast medium are frequently painful (external carotid artery, vertebral artery). No significant difference in the degree of bradycardia was caused by the two contrast media. The degree of bradycardia was also found to be poorly reproducible upon successive injections of the same contrast medium in the same patient, thus raising questions as to the suitability of this method for determining the toxicity of the contrast medium. The quality of the angiograms obtained did not differ significantly with the two media. Spasm, when it occurred during selective external carotid injections, was found to be independent of the contrast agent used, being correlated instead with the depth of distal advance of the catheter tip into the external carotid. Of the 51 patients included in the study, two patients suffered transient neurological deficit after angiography with metrizamide, and one patient suffered a permanent hemiplegia after angiography with meglumine ioxithalamate.

Aorta, Thoracic↗
PubMed1978

Effects of inhibition of prostaglandin-synthesis on renal electrolyte excretion and concentrating ability in healthy man.

In five healthy subjects inhibition of prostaglandin (PG)-synthesis with indomethacin did not significantly alter glomerular filtration, urinary flow rate or sodium and potassium excretion during control urine collection periods or i.v. hypertonic saline infusion. Saline administration was accompanied by a fall in urinary PGEI-excretion from 0.58 +/- 0.14 to 0.26 +/- 0.09 ng/min (p less than 0.05). While indomethacin had no effect on basal urinary osmolality (Uosm), renal concentrating ability following hypertonic saline or i.v. administration of 100 mU lysine-vasopressin significantly increased in the presence of indomethacin with Uosm rising from 805 +/- 25 to 970 +/- 53 mosm/L (p less than 0.01) and from 839 +/- 47 to 996 +/- 62 mosm/L (p less than 0.01), resp. Since this was not accompanied by respective changes in urinary excretion of cyclic adenosine monophosphate (cAMP) mechanisms other than PG-antagonism of vasopressin, such as decreased medullary washout of solute, may contribute to enhanced renal concentrating ability following inhibition of PG-synthesis with indomethacin.

Adult↗
PubMed1978

Third factor and edema formation.

Urine extracts as well as plasma and urine fractions from normal persons during extracellular volume expansion and from patients with edema of different origin were tested for natriuretic (rat bioassay) and antinatriferetic (frog skin) activity. Whereas the extracts and fractions from normal persons with extracellular volume expansion proved to have a distinct natriuretic and antinatriferetic effect, no such effect was observed with urine and plasma preparations from patients with sodium retention and edema. Whether or not edema formation is mediated by a loss of natriuretic activity remains still to be clarified.

Adult↗
PubMed1977

[Triamterene in the treatment of hypertension with hydrochlorothiazide and propranolol (author's transl)].

In 36 patients with essential hypertension the action and side effects of hydrochlorothiazide (25 mg/d), hydrochlorothiazide-triamterene (25 and 50 mg/d) and propranolol (160 mg/d) were investigated. Hydrochlorothiazide and hydrochlorothiazide-triamterene led to an average decrease of the systolic blood pressure by 21 and 30 mm Hg and of the diastolic pressure by 11 and 18 mm Hg. Propranolol alone decreased the systolic pressure by 35 mm Hg on average in 8 out of 16 patients. The diastolic pressure was lowered by 20 mm Hg. In the remaining 8 patients the systolic pressure, when propranolol was used alone, decreased by 21.3 mm Hg, the diastolic pressure by 11.3 mm Hg. Addition of hydrochlorothiazide-triamterene lowered pressures by a further 22.5 (systolic) and 10.6 (diastolic) mm Hg. No disturbances of the potassium or acid-base balance were observed using hydrochlorothiazide-triamterene.

Acid-Base Equilibrium↗