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Biomedical subjects

R Düsing

Publications and source records attributed to R Düsing.

At least 19 recordsLinked to original sources
PubMed1996

CV-11974, the active metabolite of TCV-116 (Candesarten), inhibits the synergistic or additive effect of different growth factors on angiotensin II-induced proliferation of vascular smooth muscle cells.

Many previous studies have demonstrated that angiotensin II (AII) type I (ATI) receptor antagonists remarkably reduced intimal lesions in rats following balloon injury. Using vascular smooth muscle cells (VSMC) in culture, we tested the hypothesis that other classical growth factors may enhance AII effects on VSMC growth, and ATI receptor antagonists may inhibit these effects. AII, platelet-derived growth factor-BB (PDGF-BB), and epidermal growth factor (EGF) caused a 3426 +/- 262%, 277 +/- 69%, and 1568 +/- 62% increase in [3H]thymidine incorporation in VSMC (mean +/- SD, n = 3), respectively. The exposure of the cells to AII in combination with PDGF-BB or EGF resulted in an approximately 2-fold or 1.5-fold elevation of the AII-dependent effect, respectively. 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-benzimi dazole-7- carboxylic acid (CV-11974), the active metabolite of the specific nonpeptide AT1 receptor antagonist (+/-)-1-cyclohexyloxycarbonyloxy)ethyl 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-benzimi dazole- 7-carboxylate (TCV-116, Candesartan), suppressed the effect of AII down to basal values, as well as reducing the synergistic effect of PDGF or the additive effect of EGF on AII-induced [3H]thymidine incorporation. AII and PDGF-BB per se induced 57 +/- 19 and 70 +/- 14% increase in VSMC number. Combination of both agonists resulted in a 2-fold increase of the AII effect on cell number. Again, CV-11974 blocked the effect of AII, as well as the additive effect of PDGF-BB on cell number. From these findings, it may be concluded that AT1 receptor antagonists may reduce or prevent the development of intimal lesions following vascular injury through inhibition of direct and indirect growth-promoting effects of AII in VSMC.

Angiotensin II↗
PubMed1995

Effects of TCV-116 and CV-11974 on angiotensin II-induced responses in vascular smooth muscle cells.

(+/-)-1-(Cyclohexyloxycarbonyloxy)ethyl 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H- benzimidazole-7-carboxylate (TCV-116, Candesartan) and its active metabolite 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H- benzimidazole-7-carboxylic acid (CV-11974) are specific nonpeptide angiotensin AT1 receptor antagonists. In the present study, the inhibitory potency of these two antagonists on the angiotensin II-induced responses in aortic vascular smooth muscle cells from Wystar Kyoto rats was investigated. The specific binding of 125I-angiotensin II to cells was inhibited by CV-11974 and TCV-116 with a half-maximal inhibitory concentration (IC50) of 3 x 10(-11) M and 1 x 10(-9) M, respectively. CV-11974 and TCV-116 inhibited the angiotensin II-induced increase in [3H]thymidine incorporation with an IC50 of 3 x 10(-10) and 5 x 10(-9) M, respectively. Both CV-11974 and TCV-116 (10(-7) M) completely blocked the angiotensin II-induced increase in c-fos mRNA. The inhibitory potency of the metabolite CV-11974 was about 30-100-fold higher than that of the prodrug TCV-116.

Angiotensin II↗
PubMed1995

[Orthostatic hypotension].

We report about a 67-year-old woman presenting with progressive orthostatic vertigo, urinary incontinence and clinical signs of Parkinson's disease. The Schellong test revealed deficient sympathetic orthostatic pressure response without an increase of plasma norepinephrine; therefore, a Shy-Drager syndrome was diagnosed. Because of inefficiency of the general measures (compressive pantyhose), the sympathomimetic agonists, and the centrally active alpha-2-antagonists, norepinephrine was administered via a miniature dosing pump. By this therapeutic regimen a marked improvement of orthostatic hypotension was achieved.

Aged↗
PubMed1995

Improved bronchial cleansing in intensive care patients with a new double-lumen catheter.

OBJECTIVES: A new double lumen catheter with a small channel for application of rinsing solution in deeper parts of the endobronchial tree was developed and its efficiency was tested in two trials. DESIGN: Comparison of the new catheter in 2 controlled studies with the traditional way of suctioning and with conventional endotracheal lavage in a randomized block design. SETTING: Intensive care unit of a university hospital. PATIENTS: In the first study, endobronchial cleansing with the new catheter was compared to the traditional way of suctioning in 12 long-time ventilated patients. In the second study, 28 ventilated patients received either conventional lavage or lavage with the new catheter. INTERVENTIONS: In the first trial the bronchial system of each patient was suctioned 25 times with a conventional technique or cleansed by using the new catheter. In the second study, patients alternatively received conventional lavage 88 times or lavage 88 times with the new catheter. MEASUREMENTS AND RESULTS: Drained secretions averaged 0.84 +/- 0.28 ml using conventional cleaning as compared to 11.02 +/- 0.84 ml with the new catheter. This was accompanied by a significant (p < 0.001) increase in PaO2 of 24.20 +/- 7.90 mmHg after 10 min compared to nearly unchanged PaO2 after normal suctioning. In the second study, suctioned volume was 2.48 +/- 0.21 ml using conventional endotracheal lavage and 10.55 +/- 0.47 ml using the new catheter. Use of the double-lumen catheter induced a significant increase in PaO2 by 30.90 +/- 3.90 mmHg within 10 min. The changes in PaO2 correlated with the drained volume. CONCLUSION: Both studies show that suctioning with the new double lumen catheter allows drainage of a larger volume of secretions and results in a greater improvement of oxygenation.

Aged↗
PubMed1995

New injectable aqueous carbamazepine solution through complexing with 2-hydroxypropyl-beta-cyclodextrin: tolerability and pharmacokinetics after intravenous injection in comparison to a glycofurol-based formulation.

The poor water solubility of the antiepileptic drug (AED) carbamazepine (CBZ) is generally considered an absolute contraindication to parenteral administration in epileptic patients. However, the water solubility of CBZ can be largely enhanced through formation of an inclusion complex with an amorphous cyclodextrin derivative, 2-hydroxypropyl-beta-cyclodextrin (HP beta CD). We studied tolerability and pharmacokinetics of an aqueous CBZ:HP beta CD solution after intravenous (i.v.) administration in dogs. For comparison, a conventional glycofurol-based solution of CBZ was used. We also administered a commercial liquid formulation of CBZ orally (p.o.). Infusion of CBZ:HP beta CD solutions or HP beta CD "placebo" formulations i.v. was well tolerated by the animals. In contrast, infusion of CBZ:glycofurol solutions and glycofurol placebo solutions induced marked behavioral and cardiovascular adverse effects. Pharmacokinetic studies indicated that glycofurol inhibited CBZ metabolism by decreasing formation of the major CBZ metabolite CBZ-10,11-epoxide (CBZ-E). With infusion of CBZ:HP beta CD 10 ml/min for 12-15 min, resulting in a CBZ dose of CBZ 5 mg/kg body weight, peak CBZ plasma levels of approximately 3.6 micrograms/ml were obtained. This relatively low peak concentration is primarily due to the rapid elimination of CBZ in dogs [half-life (t1/2) < 1 h]. Comparison of peak plasma levels determined after p.o. administration of CBZ to dogs with peak CBZ levels previously determined after p.o. administration in humans indicated that about four times higher doses are needed in dogs to attain the same peak plasma levels as in humans.(ABSTRACT TRUNCATED AT 250 WORDS)

2-Hydroxypropyl-beta-cyclodextrin↗
PubMed1995

Kinetics of Na+/H+ exchange in vascular smooth muscle cells from WKY and SHR: effects of phorbol ester.

The kinetic properties of Na+/H+ exchange were investigated in vascular smooth muscle cells (VSMC) in culture from normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Antiport activity was measured in 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein-loaded cells after nigericin-induced cytosolic acidification. Studies were performed without (control) and with pretreatment of the cells with phorbol 12-myristate 13-acetate (PMA; 200 nM). Na+/H+ exchange markedly differed between the two strains with lower Hill coefficients [1.56 +/- 0.17 (SE) vs. 2.62 +/- 0.36] and higher maximal activity (Vmax) values (55.85 +/- 5.24 vs. 31.11 +/- 2.38 mmol H+.l-1.min-1) in SHR compared with WKY cell lines. PMA markedly altered the antiport kinetics in WKY VSMC with a decrease in the Hill coefficient (1.75 +/- 0.14) without affecting Vmax (31.88 +/- 1.55 mmol H+.l-1.min-1). In VSMC from SHR, PMA had no effect on the kinetic variables investigated. Thus two kinetic abnormalities are present with respect to Na+/H+ antiport activity in VSMC from SHR compared with WKY, i.e., increased Vmax and decreased Hill coefficient. The observation that PMA does not affect the kinetics of the Na+/H+ antiport in VSMC from SHR suggests a marked degree of antiporter prestimulation in this animal model of genetic hypertension.

Animals↗
PubMed1995

Sodium-proton exchange and primary hypertension. An update.

An enhancement of sodium-proton exchange in blood cells of patients with primary hypertension has been described by various investigators. The present review summarizes some of the most recent findings regarding the enhanced sodium-proton exchanger activity in primary hypertension and discusses the potential mechanisms that may contribute to or explain these findings. Novel evidence has been accumulated on the in vivo regulation of the sodium-proton exchanger in humans, and recent findings suggest that metabolic acidosis, high NaCl intake, and circulating hormones (eg, insulin) can enhance sodium-proton exchanger activity in blood cells. However, the relative roles of such exogenous factors in the stimulation of sodium-proton exchanger activity in primary hypertension remain questionable because enhanced sodium-proton exchanger activity persists in immortalized lymphoblasts from patients with primary hypertension after prolonged cell culture. Therefore, at least in a certain group of hypertensive subjects this abnormality cannot be due to metabolic or hormonal alterations of the "hypertensive" in vivo milieu but appears to be under genetic control. Available evidence strongly argues against intrinsic changes of the sodium-proton exchanger protein itself in primary hypertension, for example, a mutation in the encoding gene. Interestingly, immortalized cells from hypertensive subjects with enhanced sodium-proton exchanger activity display a distinctly enhanced proliferation pattern that appears to be independent of this ion transport. At present we speculate that enhanced sodium-proton exchanger activity and proliferation may represent indicators of a genetically fixed enhanced intracellular signal transduction in primary hypertension that may be caused by an increased activation of pertussis toxin-sensitive G proteins.

Animals↗
PubMed1995

Thromboxane A2 and vascular smooth muscle cell proliferation.

In the present study we describe the intracellular pathways for the transmission of growth signals by the potent vasoconstricting eicosanoids prostaglandin H2 and thromboxane A2 in smooth muscle cells from rat aorta. Carbocyclic thromboxane A2 and U46619 are stable thromboxane A2 mimetics acting at the common thromboxane A2/prostaglandin H2 receptor. Carbocyclic thromboxane A2 (10(-6) mol/L) induced an approximately 2.5-fold increase in [Ca2+]i above the basal value at 25 seconds. Maximal stimulation of the 42-kD mitogen-activated protein kinase isoform by both thromboxane A2 mimetics occurred at 5 minutes. Both thromboxane A2 mimetics at a concentration of 10(-6) mol/L induced the expression of c-fos and early growth response gene-1 (egr-1) mRNA, with a maximum at 30 minutes. Carbocyclic thromboxane A2 (10(-6) mol/L) induced a 3.3-fold increase in [3H]thymidine incorporation into cell DNA above the basal value and produced a 3.5-fold elevation of platelet-derived growth factor-BB-dependent [3H]thymidine incorporation into cell DNA. Similar effects of U46619 (10(-6) to 10(-5) mol/L) alone did in combination with platelet-derived growth factor-BB on cell DNA synthesis were obtained. The thromboxane A2/prostaglandin H2 receptor antagonist SQ29548 (10(-6) mol/L) completely suppressed the mitogenic effect of both thromboxane A2 mimetics (10(-6) mol/L). Pertussis toxin (10 to 100 ng/mL) did not influence the mitogenic effects of the thromboxane A2 mimetics. Carbocyclic thromboxane A2 (10(-6) mol/L) and platelet-derived growth factor-BB (20 ng/mL) per ser caused a 44% and 100% increase in cell number, respectively. In the presence of carbocyclic thromboxane A2 (10(-6) mol/L), platelet-derived growth factor-BB induced a 152% increase in cell number. Similar results were obtained with U46619 alone or in combination with platelet-derived growth factor-BB.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1994

Hypertonic saline infusion induces activation of the lymphocyte Na+/H+ antiport and cytosolic alkalinization in healthy human subjects.

The Na+/H+ antiport is a membrane transport protein that extrudes intracellular protons in exchange for extracellular sodium. Some details of its physiological and pathophysiological role remain poorly defined. Experimental evidence suggests that the antiporter is involved in the regulation of cell volume. In the present study, we therefore investigated the activity of the lymphocyte Na+/H+ antiport in nine healthy volunteers following acute hypertonic (2.5%) saline infusion (4 mmol NaCl/kg over 120 min). Antiport activity was measured after acidifying the cells with Na+ propionate (5-40 mM) using the fluorescent dye bis-carboxyethyl carboxyfluorescein. Hypertonic saline induced significant increases in plasma osmolality (308.4 +/- 2.3 vs. 293.5 +/- 2.7 mOsm/kg; P < 0.01), serum Na+ (150.8 +/- 3.7 vs. 138.9 +/- 0.5 mmol/kg; P < 0.01), and Cl- concentrations (118.0 +/- 3.9 vs. 101.1 +/- 1.0 mmol/kg; P < 0.01). Extracellular hypertonicity was followed by a stimulated activity of the lymphocyte Na+/H+ antiport with an increase in the apparent Vmax values from 2.44 +/- 0.16 to 3.27 +/- 0.34 10(-3) s-1 (P < 0.01) and a slight rise in pK, from 6.81 +/- 0.03 to 6.87 +/- 0.03 (P < 0.05) after hypertonic saline. In addition to antiport activation, cytosolic alkalinization was observed with cytosolic pH values averaging 6.90 +/- 0.02 before and 6.99 +/- 0.02 (P < 0.01) after hypertonic saline. Our results show for the first time that acute extracellular hypertonicity in man due to hypertonic NaCl loading is associated with a stimulated lymphocyte Na+/H+ antiport activity and cytosolic alkalinization.

Adult↗
PubMed1994

Evidence for cardiovascular remodeling in a patient with Bartter's syndrome.

In a 56-year-old normotensive white male subject with a 12-year history of hypokalemic alkalosis, hyperreninemia, and aldosteronism, the diagnosis of Bartter's syndrome was established on the basis of an impaired maximal renal diluting capacity and decreased distal fractional chloride absorption [CH2O/(CH2O+CCl)]. Negative urine analysis for diuretics suggested that this renal tubular defect was not secondary to diuretic (ab)use. In this normotensive patient with hyperreninemia and secondary aldosteronism, significant cardiovascular remodeling could be observed. Thus, in spite of normal arterial blood pressure and normal left ventricular systolic function (ejection fraction > 70%), impaired left ventricular diastolic function was observed using pulsed-wave Doppler echocardiography. Moreover, duplex analysis of the common carotid artery revealed significant intima-media hypertrophy with an average intima-media diameter of 0.9 mm (normal < or = 0.6 mm). Also, forearm venous occlusion plethysmography revealed an abnormally high minimal forearm vascular resistance following a 10-min period of forearm ischemia handgrip exercise suggesting remodeling within the peripheral arterioles. Thus, in a patient with Bartter's syndrome and activated neurohormonal systems such as the renin-angiotensin system, cardiac and vascular remodeling can be observed in the absence of hypertension. In analogy to the results of experimental studies showing that angiotensin II and noradrenaline act as growth factors on cardiac and vascular cells, cardiovascular remodeling present in our patient with Bartter's syndrome may be explained by increased activity of angiotensin II and/or noradrenaline.

Arteries↗
PubMed1994

Iron-deficiency anemia as the sole manifestation of celiac disease.

We report on a 40-year-old woman with a 2-year history of iron-deficiency anemia of unknown origin. Repeated endoscopic investigations in the past had revealed no abnormality of the gastrointestinal system on macroscopic examination. Oral iron supplementation was shown to have no effect on serum iron levels and had no influence on the anemia. Upper gastrointestinal endoscopy performed at our hospital confirmed normal macroscopic findings. However, jejunal biopsies revealed subtotal villous atrophy of the mucosa of the small intestine. A strict gluten-free diet led to an increase in serum iron, resolution of the anemia, and restitution of normal mucosal architecture. Thus iron-deficiency anemia may be the lone manifestation of celiac disease.

Adult↗
PubMed1994

The lymphocyte Na+/H+ antiport: activation in primary hypertension and during chronic NaCl-loading.

Increased activity of the Na+/H+ antiport may be a major abnormality in essential hypertension. The activity of this transport system was investigated in lymphocytes from 13 patients with untreated essential hypertension (Ht) and 13 normotensive control subjects (Nt) on an ad libitum (130-170 mmol d-1) NaCl intake. Furthermore, the effects of different states of NaCl balance on lymphocyte Na+/H+ antiport were evaluated in two groups of Nt volunteers receiving 20 vs. 300 mmol d-1 (n = 8) and 85 vs. 200 mmol d-1 (n = 14) of NaCl for 1 week each and in seven Ht patients (20 vs. 300 mmol NaCl d-1 for 1 week each). Additionally, during the 20 and 300 mmol/d NaCl intake red blood cell membrane transport was studied in eight subjects. For the determination of lymphocyte antiport activity, cells were loaded with the cytosolic pH (pHi) indicator bis-carboxyethyl carboxyfluorescein (BCECF-AM) and acidified by addition of different amounts of Na(+)-propionate (5-40 mM). Initial pHi-recovery was taken as the activity of the antiport system and plotted against pHi-values after acidification. Non-linear regression analysis yielded higher 'apparent' maximal transport rates in Ht than Nt (Nt: 2.00 +/- 0.22; Ht: (3.81 +/- 0.59) x 10(-3) s-1; P < 0.025). In contrast, baseline pHi-values and pHi-values at half-maximal activity (pK) were identical in Nt and Ht. In normotensive control subjects on an NaCl intake of 20, 85, 200 and 300 mmol d-1 for 7 d, 'apparent' maximal transport rates averaged 2.75 +/- 0.20, 2.89 +/- 0.17, 2.81 +/- 0.18 and (3.62 +/- 0.25) x 10(-3) s-1, respectively. Thus, antiport activity was significantly (P < 0.05) stimulated on the 300 mmol d-1 intake as compared to the three other NaCl intakes. The extreme intakes of NaCl (20 vs. 300 mmol d-1) in normotensive volunteers did not affect the erythrocyte Na+/K+ pump, Na+/K+ cotransport and Na+/Li+ countertransport. Our study supports the concept that a group of patients with primary hypertension exhibit an activated Na+/H+ antiport. Furthermore, our data demonstrate that a chronic high intake of NaCl is associated with an increase in lymphocyte antiport activity towards the high values observed in primary hypertension.

Adult↗
PubMed1993

Platelet Na+/H+ antiport activity in patients with insulin-dependent diabetes mellitus with and without diabetic nephropathy.

The incidence of diabetic nephropathy in patients with insulin-dependent diabetes mellitus (IDDM) may depend on factors other than the quality of diabetes control. Hypertension is an additional factor associated with a high degree of renal involvement in IDDM. One abnormality consistently observed in various tissues of patients with essential hypertension is enhanced activity of the Na+/H+ antiport. In the present study we have therefore studied platelet antiport activity in 41 healthy subjects (control), in 22 patients with untreated essential hypertension (EH), and in 35 normotensive IDDM patients (type 1). Of these patients 17 exhibited signs of diabetic nephropathy (group 1) while 18 had no evidence for renal involvement of IDDM in spite of a duration of IDDM of at least 10 years (group 2). The two IDDM patient groups were undistinguishable with respect to age, body mass index, and arterial blood pressure (group 1, 117.9 +/- 2.4/78.4 +/- 1.5 mmHg; group 2, 113.9 +/- 3.6/76.1 +/- 1.8 mmHg). Antiporter activity was determined from the rate of cell volume changes induced by propionic acid. Platelet Na+/H+ exchange activity averaged 23.43 +/- 0.43 10(-3).s-1 in control subjects and was markedly elevated in EH (28.38 +/- 0.62 10(-3).s-1; P < 0.01). Antiport activity in group 2 patients without nephropathy averaged 24.54 +/- 0.57 10(-3).s-1 and was undistinguishable from the control group. However, platelet Na+/H+ antiport activity was significantly stimulated in group 1 patients with nephropathy as compared to group 2 (26.95 +/- 0.73 10(-3). s-1; P < 0.025). Our results show that renal involvement in IDDM is associated with enhanced activity of the platelet Na+/H+ antiport.

Adult↗
PubMed1993

Insulin enhances angiotensin II induced DNA synthesis in vascular smooth muscle cells of the rat.

Hypertension has a high prevalence among subjects with decreased insulin sensitivity and/or hyperinsulinemia. Furthermore, angiotensin II plays a pivotal role in the regulation of vascular tone and is known to induce hypertrophy and/or hyperplasia in vascular smooth muscle cells. In the present study, the effect of insulin on angiotensin II induced smooth muscle cell growth (Wistar-Kyoto rat) was investigated. Cell growth was assessed by the measurement of [3H]thymidine incorporation into cell DNA. Insulin in a concentration range of 1.7 x 10(-10)-1.7 x 10(-6) M lacked any effect on cell DNA synthesis. However, insulin enhanced the angiotensin II induced DNA synthesis in a concentration-dependent manner. This effect was similar in cells with a weak and in cells with a marked response in DNA synthesis to stimulation with 100 nM angiotensin II. In conclusion, insulin is able to enhance angiotensin II induced DNA synthesis and may therefore function as a growth cofactor in vascular smooth muscle cells.

Angiotensin II↗
PubMed1993

Dye and electric coupling between osteoblast-like cells in culture.

Primary cultures of osteoblast-like cells (OB) derived from calvarial fragments of newborn rats and juvenile guinea pigs formed numerous gap junctions between neighboring cells in vitro. Intracellular injection of Lucifer yellow led to a staining of up to 30 adjacent cells. Parallel intracellular recordings showed that amplitudes of stimulated membrane potential changes (4-5 mV) were closely related between coupled cells. The coupling factor, which was derived from the ratio of these amplitudes, ranged between 0.1 and 0.8. The coupling factor (1) was not dependent on the membrane potential or the injected current strength; (2) strong acidosis (pH < 6.6) and hypercapnia (pCO2 > 80 mm Hg) did not affect electric or dye coupling; (3) elevation of intracellular cAMP level was ineffective; (4) rise of the extra- and intracellular Ca2+ concentration did not effect the electric coupling; (5) the anticonvulsant drugs carbamazepine and phenytoin impaired the coupling factor up to 59%. The findings show that cell-cell communication between OB via gap junctions proved stable under various conditions which, in other tissues, were found to reduce the coupling strength of gap junctions.

1-Octanol↗
PubMed1993

Long-term insulin treatment of vascular smooth muscle cells from rat aorta attenuates the synergistic effect of insulin on angiotensin II- and epidermal growth factor-induced DNA synthesis.

1. In the present study the effects of acute and chronic insulin treatment on growth factor-induced cell growth were investigated in vascular smooth muscle cells. Cell growth was quantified by the incorporation of [3H]thymidine into cell DNA and by determination of total protein. 2. Insulin in a concentration range of 10(-9)-10(-6) mol/l had no effect on cell DNA synthesis. Insulin-like growth factor-1 in a concentration range of 10(-9)-10(-6) mol/l induced a concentration-dependent increase in total cell protein, whereas no changes in DNA synthesis were observed. 3. Acutely, insulin enhanced the mitogenic effect of epidermal growth factor and angiotensin II. Long-term treatment with 10 and 100 ng/ml insulin over 14 weeks was associated with a time-dependent reduction in this potentiating effect of insulin on growth factor-induced DNA synthesis. To evaluate the mechanism of this effect, receptor binding studies were performed with 125I-labelled insulin-like growth factor-1. No difference in the Kd value (2.1 nmol/l) for insulin-like growth factor-1 was found between untreated and chronically insulin-treated cells, whereas the maximal number of binding sites decreased from 5.9 x 10(4) (untreated cells) to 4.7 x 10(4) (10 ng/ml) and to 4.3 x 10(4) (100 ng/ml) binding sites/cell in chronically insulin-treated cells. 4. We conclude that insulin acutely enhances the mitogenic effect of various growth factors such as epidermal growth factor and angiotensin II on vascular smooth muscle cells. Long-term insulin treatment reduced the number of receptor binding sites for insulin-like growth factor-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗