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S M Bode-Böger

Publications and source records attributed to S M Bode-Böger.

62 records · Page 4Linked to original sources
PubMed1994

Long-term administration of L-arginine, L-NAME, and the exogenous NO donor molsidomine modulates urinary nitrate and cGMP excretion in rats.

OBJECTIVE: The effects of long term oral administration of L-arginine, NG-nitro-L-arginine methyl-ester (L-NAME), or molsidomine v placebo on blood pressure and the urinary excretion rates of NO3- and cyclic GMP were studied in Munich Wistar Frömter (MWF) rats. METHODS: L-arginine (2 g.kg-1 body weight, n = 8), NG-nitro-L-arginine methylester (L-NAME; 5 mg.kg-1, n = 8), or molsidomine (3 mg.kg-1, n = 8) were given in drinking water and compared with placebo (n = 8) over a period of five months. Urinary excretion rates of NO3- (by gas chromatography) and cyclic GMP (by radioimmunoassay) were assessed in monthly intervals, as well as systolic blood pressure (tail plethysmography). RESULTS: Mean basal blood pressure was 143.5(SEM 2.2) mm Hg. It was unaffected by L-arginine or molsidomine, but continuously and significantly increased during L-NAME treatment to 199.3(6.4) mm Hg (p < 0.05). Urinary excretion of NO3- increased by 20-41% v controls in L-arginine and molsidomine treated rats (p < 0.05), and decreased by 5-15% in L-NAME treated rats (p < 0.05). Urinary excretion of cyclic GMP increased by 9-38% v controls in the L-arginine and molsidomine treated groups and decreased by 5-20% in the L-NAME treated animals. Consistent with their higher blood pressure, L-NAME treated animals displayed cardiac hypertrophy. CONCLUSIONS: Determination of urinary NO3- excretion by gas chromatography is a sensitive and specific method to assess NO formation in vivo. Long term oral administration of L-arginine in MWF rats increases NO production (as assessed by the urinary excretion rates of NO3- and cyclic GMP), but does not significantly influence systolic blood pressure, whereas L-NAME induces sustained hypertension and cardiac hypertrophy due to inhibition of NO formation.

Animals↗
PubMed1994

Increased urinary nitrate excretion in rats with adjuvant arthritis.

OBJECTIVES: In rats with adjuvant arthritis measurements were taken of the urinary excretion of nitrate, reflecting endogenous nitric oxide (NO) formation, and cyclic guanosine monophosphate (cGMP). METHODS: Urinary nitrate was determined by gas chromatography, cGMP by radioimmunoassay. RESULTS: A significant (p < 0.001), more than three fold increase of urinary nitrate excretion was found in rats 20 days after induction of adjuvant arthritis compared with non-arthritic rats. There was no significant difference in urinary cGMP excretion between arthritic rats and control animals. CONCLUSION: The data suggest that the dramatic increase of urinary nitrate excretion is due to increase of NO synthesis by the inducible form of NO synthase.

Animals↗
PubMed1994

Exercise increases systemic nitric oxide production in men.

BACKGROUND: Our aim was to compare the effects of exercise on systemic nitric oxide formation, assessed from the urinary excretion rates of nitrate and of cyclic GMP, in endurance-trained and untrained men. METHODS: Ten endurance-trained and six untrained men underwent a submaximal exercise test for 30 min at 60% of their individual maximal work capacity. Urinary excretion rates of nitrate (measured using gas chromatography) and cyclic GMP (measured using a radioimmunoassay) were assessed at hourly intervals. RESULTS: Urinary nitrate excretion was comparable at rest in the two groups (104 +/- 35 and 110 +/- 19 mumol/mmol creatinine; NS), more than doubled during exercise in both groups (236 +/- 88 mumol/mmol creatinine in untrained and 252 +/- 39 mumol/mmol creatinine in trained participants; P < 0.01 for both groups) and decreased rapidly after the completion of the exercise test. Excretion of urinary cyclic GMP at rest was four times higher in the endurance-trained than in the untrained men (21 +/- 5 compared with 6 +/-1 nmol/mmol creatinine; P < 0.05). During the exercise test, GMP excretion approximately doubled in both groups (52 +/- 12 and 10 +/- 1 nmol/mmol creatinine, respectively; P < or = 0.01 for both groups) and returned to baseline at the end of the test. Urinary cyclic GMP and nitrate excretion correlated well in both groups (p < 0.05). Atrial natriuretic factor is also a stimulator of cyclic GMP formation but resting plasma levels of atrial natriuretic factor did not differ between the groups (22 +/- 3 compared with 21 +/- 4 pmol/l; NS). CONCLUSION: An acute submaximal exercise test increases the formation of nitric oxide, reflected in the increase in urinary excretion of nitrate and cyclic GMP. This increase may contribute to vasodilatation during physical exercise and at least partly explain the beneficial effects of physical training in patients with vascular diseases.

Adult↗
PubMed1993

Rapid and selective inhibition of platelet aggregation and thromboxane formation by intravenous low dose aspirin in man.

1. One of the major problems in the clinical use of low dose aspirin for the prevention of vascular occlusion is that it takes about 3-5 days to become effective, a time too long for patients with unstable angina or coronary thrombolysis. Intravenous aspirin may be expected to exert a more rapid effect, but its influence on endothelial prostacyclin synthesis is uncertain. 2. In a single-blind, randomized, prospective study, we compared the effects of a single intravenous low dose (50 mg) or high dose (500 mg) of aspirin or placebo infused over a 60 min period on platelet aggregation, platelet thromboxane A2 production and whole-body prostanoid synthesis in 10 healthy male subjects by gas chromatography-tandem mass spectrometry. 3. Before the study, blood flow rates in the basilic and subclavian veins were determined by sonographic colour velocity imaging; the infusion rate for low dose aspirin was calculated to avoid biologically effective plasma levels of aspirin in the systemic circulation. 4. Platelet aggregation induced by 1 mmol/l arachidonic acid was similarly inhibited by > 85% within 30 min after the start of the infusion of high dose or low dose aspirin, respectively, and remained suppressed for 24 h. Platelet thromboxane A2 release declined gradually after low dose aspirin, reaching a minimum of 93% inhibition after 60 min. High dose aspirin suppressed platelet thromboxane A2 release to below the detection limit after 10 min. 5. Urinary excretion of the major urinary metabolite of thromboxane A2 (2,3-dinor-thromboxane B2) was equally suppressed by both dosages of aspirin [no significant difference between high dose (-83.2%) and low dose (-67.4%)].(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Endothelin release and shift in prostaglandin balance are involved in the modulation of vascular tone by recombinant erythropoietin.

Hypertension is the main side effect developing in patients suffering from renal anemia who are treated with recombinant human erythropoietin (rhEPO). We investigated the effect of rhEPO on the vascular tone of rabbit aorta. rhEPO had no direct vasoconstrictor effect, but it enhanced norepinephrine (NE)-induced contractions of rabbit aortic rings. Relaxations to acetylcholine (ACh, 1 microM) were unaltered in the presence or absence of rhEPO, indicating that the endothelium-dependent NO pathway was not affected by rhEPO. In rings of human renal artery and rabbit aorta, rhEPO (200 U/ml) increased the synthesis of constrictor prostanoids. The cyclooxygenase inhibitors indomethacin and aspirin abolished the increase in prostanoid production. However, they did not completely suppress the rhEPO-induced enhancement of NE contractions in rabbit aorta. We further investigated the effect of rhEPO on prostanoid and endothelin-1 synthesis in cultured human endothelial cells. Endothelial cells from human umbilical veins (HUVEC) were isolated and cultured. After incubation with rhEPO, the formation of prostaglandin (PG) I2 (analyzed as its stable metabolite 6-keto-PGF1 alpha), PGF2 alpha, PGE2, thromboxane (Tx) B2, and of endothelin-1 (ET-1) was measured by radioimmunoassay (RIA). rhEPO (200 U/ml) increased the formation of PGF2 alpha and TxB2 and decreased the formation of PGI2 in HUVEC. The release of ET-1 was increased by nearly 90% in the presence of rhEPO (200 U/ml). We conclude that a shift in the balance of constrictor and relaxing prostanoids as well as an increased synthesis of ET-1 may contribute to the hypertensive side effect of rhEPO therapy. ET-1 may at least in part be responsible for the unexpectedly low inhibitory effect of indomethacin on rhEPO-enhanced contractions of rabbit aorta.

Animals↗
PubMedDate not supplied

Effects of very low dose and enteric-coated acetylsalicylic acid on prostacyclin and thromboxane formation and on bleeding time in healthy subjects.

OBJECTIVE: Low dose acetylsalicylic acid (ASA) is widely used as an anti-aggregatory agent in the primary and secondary prevention of cardiovascular diseases. In an effort to spare prostacyclin formation and to reduce gastrointestinal side-effects, both very low doses and enteric-coated formulations of ASA have been introduced. However, it still remains unclear whether these different formulations and dosages are equally effective with respect to inhibition of platelet aggregation and thromboxane A2 (TXA2) formation. METHODS: In a randomized study, we therefore investigated the effects of 100 mg ASA plain (p), 100 mg ASA enteric-coated (ec) and 40 mg ASA (p) to 36 healthy male subjects given for 7 days on platelet aggregation and endogenous prostanoid formation rates. Platelet aggregation and platelet TXB2 release in platelet rich plasma (PRP) and serum TXB2 and 6-keto-PGF1alpha levels were determined at baseline and after 7 days of each medication. The urinary metabolites of TXA2 (2,3-dinor-TXB2) and prostacyclin (2,3-dinor-6-keto-PGF1alpha) were measured by gas chromatography/tandem mass spectrometry in 24-h-urines at baseline and on day 7 of each medication. RESULTS: Collagen-induced platelet aggregation was 73.1+/-1.6% of maximal aggregation at baseline. It was inhibited by 68.9%, 58.6% and 24.0% by ASA 100 mg plain, 100 mg enteric-coated, and 40 mg plain on day 7, respectively. Platelet TXB2 release was 11592.0+/-367.5 pg x ml(-1) PRP. It was inhibited by 90.1%, 86.5%, and 55.2% by ASA 100 mg plain, 100 mg enteric-coated, and 40 mg plain, respectively. Serum TXB2 was almost completely reduced on day 7 by 100 mg ASA, but not by 40 mg ASA; serum 6-keto-PGF1alpha was slightly, but significantly reduced in all three groups. Urinary 2,3-dinor-TXB, excretion was 196.0+/-41.5 pg x mg(-1) creatinine at baseline. It was reduced by 80.3% and 79.1% by ASA 100 mg plain and enteric-coated, respectively (each P < 0.05 versus baseline), but only by 55.4% by ASA 40 mg plain (P < 0.05 versus both formulations of ASA 100 mg). CONCLUSIONS: Our present data show that the plain and enteric-coated formulations of 100 mg ASA are equally effective in inhibiting platelet aggregation, platelet thromboxane production, and urinary 2,3-dinor-TXB2 excretion rates. In contrast, a very low dose of 40 mg ASA was significantly less effective in inhibiting these indices of platelet activation in healthy human subjects. ASA enteric-coated 100 mg may be a useful alternative to 100 mg ASA (p) in patients with gastrointestinal side-effects, whereas 40 mg ASA (p) may be too low to inhibit sufficiently platelet activity in patients with cardiovascular diseases in whom platelet activity is increased.

Adult↗