PubMed Health⌕ Search

Biomedical subjects

R J Gryglewski

Publications and source records attributed to R J Gryglewski.

At least 19 recordsLinked to original sources
PubMed1992

Mechanisms of the endothelium-dependent relaxation induced by NG-hydroxy-L-arginine.

There are three mechanisms by which NG-hydroxy-L-arginine (L-HOArg) induces endothelium-dependent relaxations. L-HOArg is a substrate for the constitutive nitric oxide (NO) synthase present in endothelial cells (ECs). It reacts with NO released from EC to form a potent and more stable vasodilator. Moreover, it induces a relatively stable, EC-dependent relaxation that is not blocked by the inhibitors of NO synthesis. Subsequently, we have investigated the effects of hydroxyguanidine (HOG) on the biological activity of endothelium-derived relaxing factor (EDRF). HOG potentiated the relaxant responses of rabbit aortic strips to EDRF released from EC by adenosine diphosphate (ADP) or bradykinin as well as those induced by authentic NO. Importantly, it was not a substrate for NO synthesis and it did not affect the generation of prostacyclin by ECs. Thus, the effects of HOG were due to the chemical reaction of HOG with NO released from ECs and the formation of a more stable vasodilator. Moreover, HOG augmented not only agonist-triggered, but also flow-induced, EC-dependent relaxation and both effects of HOG were abolished by NG-nitro-L-arginine methyl ester (L-NO2-Arg). In contrast, the EC-dependent relaxation induced by L-HOArg was not inhibited by L-NO2Arg. Moreover, it was not affected by the removal of extracellular Ca2+, but was blocked by oxyhemoglobin and potentiated by superoxide dismutase. These results demonstrate the involvement of the hydroxyguanidino moiety of L-HOArg in its reaction with NO. Moreover, they strongly support the notion that nitrix oxide mediates both the agonist-triggered and flow-induced endothelium-dependent relaxation.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases↗
PubMed1992

Modulation of the pharmacological actions of nitrovasodilators by methylene blue and pyocyanin.

1. In superfused precontracted strips of rabbit aorta, methylene blue (MeB) or pyocyanin (Pyo, 1-hydroxy-5-methyl phenazinum betaine) at concentrations of 1-10 microM inhibited relaxations induced by endothelium-derived relaxing factor (EDRF), glyceryl trinitrate (GTN), S-nitroso-N-acetyl-penicillamine (SNAP) or 3-morpholino-sydnonimine (SIN-1). However, the vasorelaxant actions of sodium nitroprusside (NaNP) or sodium nitrite (NaNO2) were enhanced by MeB or Pyo. Oxyhaemoglobin (HbO2, 1 microM) inhibited the activities of EDRF and all of the nitrovasodilators studied. Vascular preparations were not relaxed by Pyo unless pretreated with NaNP (0.05-10 microM). 2. In bathed, precontracted rings of rabbit aorta, Pyo (10 microM) produced a shift to the left of the cumulative concentration-response curve for NaNP (0.01-10 microM). The rise in guanosine-3':5'-cyclic monophosphate (cyclic GMP) content of aortic tissue was also enhanced. 3. The vasorelaxant potency of NaNP (30 microM) at pH 5-8 and at 37 degrees C remained unchanged over 2.5 h while a solution of SNAP (30 microM) progressively lost its biological activity over 60 min. The in vitro degradation of the biological activity of SNAP was accelerated by MeB (150 microM) or Pyo (150 microM), whereas the vasorelaxant potency NaNP (30 microM) was doubled when incubated with MeB or Pyo. 4. In human platelet-rich plasma, MeB or Pyo (0.3-3.0 microM) uncovered an anti-aggregatory action of subthreshold concentrations of NaNP (4-8 microM). This was abrogated by HbO2 (10 microM).5. We conclude that MeB or Pyo differ from HbO2 in their mode of interaction with nitrovasodilators.HbO2 scavenges nitric oxide that is released from all types of nitrovasodilators. MeB and Pyo exert a similar action towards organic nitrovasodilators (e.g. SNAP, SIN-1). However, the pharmacological actions of inorganic nitrovasodilators (e.g. NaNP or NaNO2) are potentiated by MeB and Pyo owing to facilitation of the intracellular release of nitric oxide from the inorganic nitrovasodilators.

Animals↗
PubMed1992

The endothelium-dependent and the endothelium-independent vasodilators in the isolated, perfused guinea pig heart.

The endothelium-dependent (acetylcholine, bradykinin, substance P) and the endothelium-independent (gliceryl trinirate, 3-morpholinsydnominine, sodium nitroprusside) vasodilators were studied in the Langendorff-perfused heart of the guinea pig. The involvement of prostanoids and EDRF in the endothelium-dependent responses were assessed by using indomethacin, an inhibitor of cyclooxygenase, and NG-nitro-L-Arginine, an inhibitor of NO synthase. The endothelium-independent agents were used as reference compounds. Both indomethacin and NG-nitro-L-Arginine elevated significantly baseline coronary perfusion pressure, indicating that prostanoids (most likely PGI2 and PGE2) and EDRF modulate the resting tone of the guinea pig coronary circulation. NG-nitro-L-Arginine, but not indomethacin, considerably reduced receptor-stimulated responses. It is concluded that acetylcholine, bradykinin or substance P-induced vasodilation is mediated by EDRF. In contrast, prostanoids do not contribute to endothelium-dependent responses. In addition, short-term tachyphylaxis to bolus injection of gliceryl trinitrate but not of sodium nitroprusside was demonstrated, suggesting that this preparation may be of value for studying nitrate tolerance.

Animals↗
PubMed1979

Successful therapy of advanced arteriosclerosis obliterans with prostacyclin.

Five patients with advanced arteriosclerosis obliterans of the lower extremities, as evidenced by resting pain, ischaemic ulcers, and focal necrosis, received intra-arterial infusions of prostacyclin at doses of 5--10 ng/kg/min for 72 h. Within 2 days of termination of the infusion, pain at rest had disappeared in all patients. In three of the five, the necrosis had completely regressed and the ischaemic ulcers healed within 2 months. The other two patients showed considerable improvement. Prostacyclin therapy was not associated with changes in the radiographic appearance of the major blood-vessels. However, muscle blood-flow, as measured by xenon-133 clearance, was significantly increased both during prostacyclin infusion and for the 6 weeks of measurement after its termination.

Aged↗
PubMed1979

Preparation and biochemical properties of PGH3.

PGH3 was biosynthesised from all-cis-5,8,11,14,17-eicosapentaenoic acid (20:5 omega 3) by an acetone-pentane powder of ram seminal vesicles and its structure was confirmed by GLC-MS after its reduction to PGF 3 alpha. PGH3 was transformed by horse platelet microsomes to TXB3, and by aortic microsomes to delta 17-6-keto-PGF 1 alpha. The structures of these compounds were confirmed by GLC-MS.

Animals↗
PubMed1979

Endogenous mechanisms which regulate prostacyclin release.

When infused intravenously into anaesthetized cats angiotensin II (1--4 micrograms/kg) released into the circulation an unstable substance that caused de-aggregation of platelet clumps, relaxed a strip of bovine coronary artery, and its release was blocked by aspirin and indomethacin. Because of these characteristics this substance is likely to be prostacyclin. Catecholamines and phenylephrine did not induce the release of prostacyclin. It is suggested that a chemical modification of the molecule of angiotensin II may render a peptide with little hypertensive properties which will be an activator of prostacyclin biosynthesis.

Angiotensin II↗
PubMed1978

Thromboxane generation and platelet aggregation in survivals of myocardial infarction.

Arachidonic acid (AA)-induced platelet aggregation was studied in platelet-rich plasma of 30 male patients who survived myocardial infarction and in 30 healthy men of similar age. Mean platelet aggregation thresholds to AA were 746 +/- 62 micrometer, and 869 +/- 57 micrometer, respectively. Only in 2 healthy subjects, but in 12 patients, irreversible platelet aggregation was induced consistently with low concentrations of AA, under 500 micrometer. The rate of conversion of AA to thromboxane A2 (TXA2) by platelets of these patients was augmented. Furthermore, less endogenous TXA2 was required to trigger aggregation of their platelets as compared to the controls. We have also shown that in platelet-poor plasma of these patients with "hyperreactive" platelets there exists a transferable factor which makes platelets of healthy subjects more prone to aggregatory action of AA. It is proposed that the assessment of platelet aggregability with AA provides a tool for identifying a subgroup of patients with coronary heart disease who might substantially benefit from the secondary preventive treatment with aspirin and with other antiplatelet drugs which inhibit the generation of TXA2 in platelets.

Adult↗
PubMed1978

Lungs as a generator of prostacyclin--hypothesis on physiological significance.

In vivo anti-platelet de-aggregatory activity of exogenous prostacyclin is enhanced after its passage through the pulmonary circulation of anaesthetized cats, probably because of a concomitant generation of endogenous prostacyclin by the lungs. Evidence is also presented that perfused lungs of guinea pigs and rats spontaneously release considerable amounts of prostacyclin. It is therefore postulated that a continuous biosynthesis of prostacyclin by pulmonary endothelium is a general physiological phenomenon, while the generation of thromboxane A2 by lungs occurs in response to pathological stimuli. Coronary and cerebral arteries are supposed to benefit from this hormonal function of the lungs.

Animals↗