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Biomedical subjects

Christian Delles

Publications and source records attributed to Christian Delles.

31 records · Page 2Linked to original sources
PubMed2003

Functional relevance of aldosterone for the determination of left ventricular mass.

In experimental studies, the importance of aldosterone for the development of left ventricular (LV) hypertrophy has been demonstrated. In 120 healthy Caucasian men (aged 25 +/- 3 years; blood pressure, 134 +/- 15/86 +/- 12 mm Hg), we determined LV mass (2-dimensionally guided M-mode echocardiography), urinary aldosterone concentration, and the response of aldosterone to angiotensin II infusion (3.0 ng/kg/min). Seventy-six volunteers took part in a follow-up visit after 2 years when urinary aldosterone concentration and LV mass were determined again. At follow-up, LV mass increased in 42 subjects (by 33 +/- 26 g), whereas in 34 subjects LV mass decreased (by 27 +/- 22 g). Between the 2 groups, only the change in urinary aldosterone concentration over time was significantly different (group with increased LV mass had an increase in urinary aldosterone concentration by 2.5 +/- 5.4 microg/day; group with decreased LV mass had a decrease in urinary aldosterone concentration by 0.7 +/- 4.6; p <0.01 between groups). In accordance, we found significant correlations between changes in LV mass and changes in urinary aldosterone concentration (r = 0.29, p <0.05) and between changes in LV mass and the response of aldosterone to angiotensin II at baseline (r = 0.25, p <0.05). Both changes in aldosterone concentration over time and the response of aldosterone to angiotensin II were related to changes in LV mass over time. These data underscore the importance of aldosterone for the development of LV hypertrophy. This process is already evident in young subjects with apparently small changes in LV mass over a mean follow-up period of 2 years.

Adult↗
PubMed2003

Direct comparison of the effects of valsartan and amlodipine on renal hemodynamics in human essential hypertension.

BACKGROUND: To elucidate the renoprotective mechanism of AT(1)-receptor blockers, we compared the effects of the AT(1)-receptor blocker valsartan with those of the calcium channel blocker amlodipine on renal hemodynamics and microcirculation. METHODS: A total of 58 patients (50.2 +/- 9.0 years) with mild to moderate essential hypertension were included in a randomized, double-blind study to receive either valsartan (80 to 160 mg) or amlodipine (5 to 10 mg). Renal plasma flow (RPF) and glomerular filtration rate (GFR) were measured before and after 8 weeks of treatment. Glomerular hydrostatic pressure (P(Glo)) and resistances of the afferent (R(A)) and efferent (R(E)) arterioles were calculated according to the Gomez formulas. RESULTS: Blood pressure control was similar in both groups. RPF did not change with either treatment. In contrast, GFR increased with amlodipine (+8 +/- 14 mL/min; P <.01) but was preserved with valsartan. Amlodipine caused a more marked increase in the R(E)/R(A) ratio than valsartan (+0.26 +/- 0.26 v +0.13 +/- 0.24, P <.05), which was paralleled by an increase in P(Glo) in patients treated with amlodipine (+1.9 +/- 4.3 mm Hg; P <.05) but not in those treated with valsartan. CONCLUSIONS: At similar blood pressure control, valsartan maintained GFR and P(Glo), whereas amlodipine led to glomerular hyperfiltration and an increase in P(Glo). The results might explain the favorable renal outcome with AT(1)-receptor blocker therapy.

Amlodipine↗
PubMed2003

The C242T p22phox polymorphism and endothelium-dependent vasodilation in subjects with hypercholesterolaemia.

Oxidative stress plays a major pathogenetic role in cardiovascular disease. The C242T variant of the CYBA gene encoding the p22phox subunit of the NAD(P)H oxidase, a major source of superoxide production, has been shown to be associated with coronary artery disease and with vascular superoxide production in human veins ex vivo. Since superoxide degrades nitric oxide (NO), we hypothesized that the C242T variant influences endothelium-dependent vasodilation of the human forearm vasculature in vivo. In the present study, 90 subjects with elevated cholesterol levels were stratified for the C242T polymorphism of the CYBA p22phox gene. Endothelium-dependent and -independent vasodilation were assessed by plethysmographic monitoring of forearm blood flow responses to intra-arterial infusion of acetylcholine and sodium nitroprusside respectively. N(G)-Monomethyl-L-arginine (L-NMMA) was infused to analyse NO-mediated basal vascular tone. Baseline parameters (age, gender, blood pressure, body mass index, cholesterol level) were similar across the genotypes. No differences in forearm blood flow responses to the intra-arterial infusion of acetylcholine, sodium nitroprusside or L-NMMA were found across the CYBA p22phox genotypes. Our sample size of n =90 had a power of >80% (beta=0.20) with a P value of <0.05 (alpha=0.05) to detect a difference greater than 156% in the forearm blood flow response to acetylcholine across genotypes (S.D. 336%; average increase in forearm blood flow=514%). In conclusion, at a power of 80%, our study excludes a major effect of the C242T CYBA p22phox polymorphism on acetylcholine-mediated endothelium-dependent vasodilation and basal NO-mediated vascular tone of the human forearm circulation in subjects with hypercholesterolaemia.

Acetylcholine↗
PubMed2003

Vitamin C augments the renal response to L-arginine in smokers.

BACKGROUND: In the coronary and the forearm circulations, endothelium-dependent vasomotion is impaired in smokers, but can be augmented by -arginine or vitamin C. We examined whether smoking similarly affects the renal circulation. METHODS: In 20 smokers (age 26 +/- 4 years) and in 20 non-smokers (age 28 +/- 3 years) changes of renal plasma flow (RPF), glomerular filtration rate (GFR), blood pressure and heart rate in response to the subsequent intravenous infusions of N(G)-monomethyl--arginine (L-NMMA), -arginine and -arginine plus vitamin C were studied by use of a constant infusion input clearance technique. RESULTS: Systemic haemodynamic parameters did not differ between smokers and non-smokers during each experimental phase. At baseline, RPF and GFR were similar between the groups. The infusion of L-NMMA led to a similar decrease of RPF, while GFR did not change in either group. During the infusion of -arginine RPF increased similarly. Finally, the co-infusion of -arginine plus vitamin C led to a significantly greater increase of RPF (+277 +/- 395 vs +79 +/- 76 ml/min, P = 0.03) and GFR (+12.1 +/- 10.6 vs +3.4 +/- 11.2 ml/min, P = 0.02) in smokers as compared to non-smokers. CONCLUSIONS: L-NMMA-induced vasoconstriction of the renal vasculature was similar in smokers compared to non-smokers. -arginine alone induced a similar increase of RPF. The co-infusion of vitamin C and -arginine led to a greater increase of RPF and GFR in smokers. This might suggest that oxidative stress is increased in the renal vasculature of smokers.

Adolescent↗
PubMed2003

L-arginine-induced vasodilation of the renal vasculature is not altered in hypertensive patients with type 2 diabetes.

OBJECTIVE: Diabetes, arterial hypertension, hypercholesterolemia, and aging are associated with endothelial dysfunction in various vasculatures. Endothelium-dependent vasodilation of the renal vasculature cannot be easily assessed, but infusion of L-arginine, the substrate of endothelial nitric oxide synthase, leads to an increase in renal plasma flow (RPF) in humans. We have examined the effect of L-arginine infusion on renal hemodynamics in hypertensive patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Twenty-three elderly patients with type 2 diabetes (age, 65 +/- 6 years; HbA(1c), 7.8 +/- 1.6%) with coexisting arterial hypertension (158 +/- 19/83 +/- 11 mmHg) and elevated cholesterol levels (total cholesterol, 215 +/- 33 mg/dl) were examined. These patients were compared with a young and healthy reference group (n = 20; age, 26 +/- 2 years). The effect of L-arginine infusion (100 mg/kg over 30 min) on RPF and glomerular filtration rate were measured using the constant input clearance technique with p-aminohippurate and inulin, respectively. RESULTS: L-arginine infusion similarly influenced renal hemodynamics in patients and reference subjects: RPF increased by 7 +/- 11 and 7 +/- 11% in diabetic and reference subjects, respectively (P = NS). Other parameters of renal hemodynamics such as glomerular filtration rate (5 +/- 5 vs. 4 +/- 4%) and filtration fraction (-1 +/- 8 vs. -1 +/- 9%) were not significantly different between diabetic and reference subjects, too. CONCLUSIONS: L-arginine-induced vasodilation of the renal vasculature is not different between a group of hypertensive diabetic patients and a young, healthy reference group. These data were obtained using low-dose L-arginine infusion.

Aged↗
PubMed2002

Assessment of endothelial function of the renal vasculature in human subjects.

BACKGROUND: L-Arginine, the substrate of nitric oxide (NO) synthase, and N(G)-monomethyl-L-arginine (L-NMMA), a competitive inhibitor of endothelial NO synthase, are used to analyze endothelial function of the renal vasculature. However, little is known about the appropriate dose of L-arginine to be used and the duration of action of L-arginine and L-NMMA. METHODS: Twenty-nine healthy male subjects (age, 27+/-1 years) were examined. In protocol 1 (N = 17), L-arginine at low (100 mg/kg) and high dose (250 mg/kg), and high-dose L-arginine combined either with L-NMMA (total dose, 4.25 mg/kg; N = 9) or placebo (N = 8) were given. In protocol 2 (N = 12), L-NMMA was given before L-arginine infusion (100 mg/kg). Glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured at rest and at the end of each infusion step. RESULTS: In protocol 1, L-arginine dose dependently increased RPF and GFR (RPF: 599+/-19 v 630+/-18 v 690+/-24 mL/min, P <.05; GFR: 111+/-3 v 115+/-3 v 121+/-3 mL/min, P <.01; for baseline, L-arginine 100 mg/kg and 250 mg/kg, respectively). However, these changes could not be antagonized by coinfusion of L-NMMA to L-arginine 250 mg/kg: RPF and GFR remained unchanged in both the placebo and the L-NMMA group. In protocol 2, L-NMMA decreased RPF (492+/-18 v 567+/-27 mL/min, P <.01) and increased GFR (122+/-4 v 118+/-3 mL/min, P <.05). These changes could only be partially reversed by subsequent infusion of L-arginine (RPF: 533+/-15 mL/min; GFR: 121+/-4 mL/min; both parameters P = NS v L-NMMA and v baseline). CONCLUSIONS: L-arginine at a dose of 100 mg/kg is sufficient to analyze endothelial function of the renal vasculature. The prolonged effect of L-NMMA and L-arginine must be taken into account in study protocols using both substances. Thus, stimulation and blockade of NO synthase cannot be examined in the same protocol.

Adult↗
PubMed2002

Angiotensin converting enzyme inhibition and angiotensin II AT1-receptor blockade reduce the levels of asymmetrical N(G), N(G)-dimethylarginine in human essential hypertension.

BACKGROUND: Asymmetrical N(G), N(G)-dimethylarginine (ADMA) is associated with impaired endothelium-dependent vasodilation in humans. METHODS: Twenty young, male, mildly hypertensive subjects were included in a randomized, double-blind, fourfold cross-over study with placebo, enalapril (20 mg/day), eprosartan (600 mg/day), or a combination of both drugs (10 and 300 mg/day, respectively) each over 1 week, followed by a 2-week wash-out phase. After each treatment phase, ADMA concentration was measured. RESULTS: ADMA concentration was 1.69+/-0.59 micromol/L in the placebo phase, and was significantly lower in the enalapril, eprosartan, and combination phases (1.41+/-0.29, 1.42+/-0.43, and 1.38+/-0.30 micromol/L, respectively; all P < 0.05 v placebo). Changes in ADMA levels were independent of the drugs' action on blood pressure (BP). CONCLUSIONS: Levels of ADMA were reduced with enalapril and eprosartan therapy. Our results suggest a specific action of these drugs on ADMA levels that is independent of BP.

Acrylates↗
PubMed2002

Effects of enalapril and eprosartan on the renal vascular nitric oxide system in human essential hypertension.

BACKGROUND: Experimental data in humans on the contribution of angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor blockers to the nitric oxide system of the renal vasculature are inconsistent. Enalapril and eprosartan, alone and in combination, were used to determine their short-term effects on the renal nitric oxide system and renal hemodynamics of human subjects with essential hypertension. METHODS: Twenty male, white patients (27 +/- 1 years) with mild essential hypertension (143 +/- 11/95 +/- 6 mm Hg) were included in a double-blind, randomized, placebo-controlled, fourfold cross-over study with placebo, enalapril (20 mg/day), eprosartan (600 mg/day), or combination of both drugs (10 and 300 mg/day, respectively) each over a one week period followed by a two-week washout phase. After each study phase the glomerular filtration rate (GFR) and renal plasma flow (RPF) were determined. Basal nitric oxide synthesis of the renal vasculature was assessed by the decrease in RPF after inhibition of nitric oxide synthase with NG-monomethyl-L-arginine (L-NMMA; 4.25 mg/kg). RESULTS: After one week of therapy, the combination therapy decreased casual blood pressure by 5 +/- 2/3 +/- 1 mm Hg versus placebo (P < 0.01). Neither enalapril alone (-2 +/- 2/1 +/- 2 mm Hg, NS vs. placebo) nor eprosartan alone (-1 +/- 1/0 +/- 2 mm Hg, NS vs. placebo) had a clear-cut significant effect on casual blood pressure. In the combination phase, RPF increased by 123 +/- 36 mL/min (P < 0.01). Neither enalapril alone (+59 +/- 46 mL/min, P = 0.21) nor eprosartan alone (+113 +/- 51 mL/min, P = 0.06) had a clear-cut significant effect on RPF. Changes of RPF induced by treatment correlated with the L-NMMA induced decrease in RPF in the combination (r = 0.70, P < 0.01) and eprosartan phase (r = 0.86, P < 0.001), but not in the enalapril phase (r = -0.44, P = 0.10). Renal vascular resistance was reduced by each active treatment with the most prominent reduction in the combination phase. GFR was unaffected by any treatment. CONCLUSIONS: In contrast to the effects of either substance alone, a combination of half the dose of eprosartan with half the dose of enalapril had a prominent effect on renal perfusion. The effects of eprosartan on RPF are mediated, at least in part, by an increased bioavailability of nitric oxide in the renal vasculature.

Acrylates↗
PubMed2002

Altered aldosterone response to salt intake and angiotensin II infusion in young normotensive men with parental history of arterial hypertension.

OBJECTIVE: An increased sensitivity to angiotensin II (Ang II) has been observed in patients with established hypertension. In the current study we tested whether young normotensive subjects with positive family history of arterial hypertension exhibit an increased sensitivity to Ang II, thereby potentially contributing to the pathogenesis of essential hypertension in these subjects. METHODS AND DESIGN: Normotensive young men (25 +/- 2 years) with positive family history (PFH) (n = 28) and negative family history (NFH) (n = 60) of arterial hypertension were investigated to study aldosterone response, and systemic and renal haemodynamic changes (p-aminohippurate- and inulin-clearance) to Ang II infusion (0.5 and 3.0 ng/min per kg). In addition, aldosterone response to salt loading (5 g/day for 1 week) was analysed. RESULTS: Ambulatory blood pressure (ABP) (mean: 84 +/- 4 versus 83 +/- 4 mmHg; NS), body mass index (23.5 +/- 2.5 versus 24.1 +/- 2.4 kg/m(2); NS), and urinary sodium excretion (191 +/- 55 versus 170 +/- 73 mmol/24 h; NS) did not differ between PFH and NFH at baseline. Changes in BP, urinary sodium and potassium excretion were similar between PFH and NFH in response to salt loading. However, salt loading did not result in an adequate suppression of aldosterone in PFH compared with NFH (8 +/- 62 versus -32 +/- 39 pg/ml; P < 0.001). Baseline values and changes in mean arterial BP (NFH: +13.4 +/- 7.6; PFH: +14.4 +/- 5.3 mmHg; NS), renal plasma flow (NFH: - 113 +/- 68; PFH: - 122 +/- 64 ml/min; NS) and glomerular filtration rate (NFH: +5.0 +/- 5.3; PFH: +4.2 +/- 8.3 ml/min; NS) in response to Ang II (3.0 ng/min per kg) were similar between the two groups. In contrast, the increases in serum aldosterone (PFH: 63.6 +/- 70.1 versus NFH: 37.7 +/- 46.8 pg/ml; P < 0.05) and urinary potassium excretion (PFH: 0.05 +/- 0.1 versus NFH: -0.01 +/- 0.07 mmol/min; P < 0.05) 30 min after stopping Ang II infusion were more pronounced and prolonged in PFH than in NFH. CONCLUSIONS: Our findings suggest that young normotensive subjects with parental history of arterial hypertension are characterized by an inadequate suppression of aldosterone production in response to salt loading and an exaggerated and prolonged hyper-responsiveness of aldosterone secretion in response to Ang II. This might contribute to the increased risk for the development of essential hypertension in subjects with positive family history of arterial hypertension.

Adult↗