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H L Zhou

Publications and source records attributed to H L Zhou.

27 records · Page 2Linked to original sources
PubMed1991

Relationship between cyclic guanosine monophosphate accumulation and relaxation of canine trachealis induced by nitrovasodilators.

The role of cyclic GMP (cGMP) in mediating relaxation of canine trachealis produced by nitrovasodilators (NVDs), compounds that activate guanylate cyclase, was examined. Sodium nitroprusside (SNP) produced a concentration-dependent relaxation of the canine trachealis that was accompanied by a concentration-related increase in cGMP content. In time course studies, relaxation of isolated trachealis strips induced by 30 microM SNP was paralleled by an increase in cGMP that reached a maximum of 18-fold above basal levels within 2 min. Zaprinast, an inhibitor of the cGMP-specific phosphodiesterase, potentiated both SNP-induced relaxation and cGMP accumulation. A cell-permeable analog of cGMP, 8-bromo-cGMP, mimicked the relaxant effects of SNP. Also assessed were the effects of methylene blue, an agent that inhibits soluble guanylate cyclase activity, and hemoglobin, an agent that competitively binds NO-containing compounds. In these experiments, tissues were pretreated with the above agents for 10 min, contracted with 1 or 3 microM methacholine, and then relaxed by the cumulative addition of SNP or two other NVDs, S-nitroso-N-acetyl-penicillamine (SNAP) and glyceryl trinitrate (GTN). Tissues were flash-frozen after adding the final concentration of the various NVDs and assayed for cGMP. Methylene blue and hemoglobin suppressed both cGMP accumulation and relaxation in response to SNAP and GTN. in contrast, methylene blue and hemoglobin inhibited SNP-induced cGMP accumulation but, paradoxically, potentiated SNP-induced relaxation. The results of this study generally support a role for cGMP in NVD-induced relaxation of airway smooth muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1991

Role of cyclic nucleotide phosphodiesterase isozymes in intact canine trachealis.

The role of individual cyclic nucleotide phosphodiesterase (PDE) isozymes in regulating cAMP and cGMP content in intact canine trachealis was examined using isozyme-selective and nonselective PDE inhibitors. The inhibitors used in this study were characterized previously [Mol. Pharmacol. 37:206-214 (1990)] and included: 1) zaprinast, an inhibitor (Ki = 0.1 microM) of the cGMP-specific PDE (cAMP Km = 135 microM; cGMP Km = 4 microM); 2) SK&F 94120, an inhibitor (Ki = 7 microM) of the cGMP-inhibited PDE (cAMP Km = 0.3 microM; cGMP Km = 8 microM); 3) Ro 20-1724, an inhibitor (Ki = 5 microM) of the cAMP-specific PDE (cAMP Km = 4 microM; cGMP Km = 40 microM); and 4) 3-isobutyl-1-methylxanthine (IBMX), a nonselective PDE inhibitor (IC50 = 1-30 microM). In addition to the aforementioned isozymes, canine trachealis contains a Ca2+/calmodulin-stimulated PDE (cAMP Km = 1 microM; cGMP Km = 2 microM) and a GMP-stimulated PDE (cAMP Km = 93 microM; cGMP Km = 60 microM), for which selective inhibitors are not available. Isolated canine trachealis strips were contracted with methacholine and exposed to various concentrations of PDE inhibitors, before being relaxed by the cumulative addition of isoproterenol, an adenylate cyclase activator, or sodium nitroprusside, a guanylate cyclase activator. At the completion of the concentration-response studies, tissues were flash-frozen and assayed for cyclic nucleotide content. Neither isoproterenol-induced relaxation nor cAMP accumulation was altered by zaprinast, but both of these responses were potentiated by pretreatment of tissues with either SK&F 94120 or Ro 20-1724. The effects of SK&F 94120 and Ro 20-1724 were additive, and the combination of SK&F 94120, Ro-1724, and IBMX had no greater effect on the responses to isoproperenol than did either IBMX alone or the combination of SK&F 94120 plus Ro 20-1724. In contrast, zaprinast potentiated sodium nitroprusside-induced relaxation and cGMP accumulation, whereas neither SK&F 94120 nor Ro 20-1724 altered these responses. IBMX produced a greater potentiation than did zaprinast, and the combination of zaprinast and IBMX had a greater effect than either agent alone. The results of this study suggest that the cGMP-inhibited and cAMP-specific PDEs are responsible for cAMP hydrolysis in intact canine trachealis, whereas cGMP hydrolysis is mediated by the cGMP-specific PDE as well as the Ca2+/calmodulin-stimulated PDE and/or the cGMP-stimulated PDE.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1990

[Effects of neutrophils on histamine release from mast cells].

To determine whether neutrophils (NP) contribute to immediate anaphylaxis, the effects of NP on histamine release from mast cells (MC) were studied and changes in the NP morphology were investigated. When rat peritoneal MC and pleural NP collected from actively sensitized rats were mixed and challenged with antigen (trichosanthin), histamine release from MC was significantly increased. This promotive effect of NP on antigen-induced histamine release from MC was dosage-dependent. The observation of scanning and transmission electron microscopy showed that NP were activated and secretion was resulted. It is suggested that NP may be activated in immediate anaphylaxis and secrete some mediators which could promote histamine release from MC. Quercetin may inhibit the promotive effect of the NP on histamine release and the secretion of the NP while ketotifen and isoproterenol have no influence on this promotive effect.

Animals↗
PubMed1989

Brain natriuretic peptide (BNP) causes endothelium-independent relaxation and elevation of cyclic GMP in rat thoracic aorta.

The novel neuropeptide, brain natriuretic peptide (BNP), causes concentration-dependent relaxations in rat isolated arterial rings. The pD2 value of BNP in rat thoracic aorta is 8.05 +/- 0.06, almost identical to the pD2 value of atrial natriuretic peptide (the 28 amino acid peptide, rat sequence, AP-28, 8.11 +/- 0.08), indicating that BNP and ANP have the same potency in relaxing thoracic aorta. In addition, BNP is equally potent at causing relaxation in abdominal aorta and mesenteric and renal arteries. However, BNP is less potent in causing vasorelaxation in the common iliac and femoral arteries and shows no relaxant effects in caudal arteries. This pharmacological profile of BNP in different rat arteries is very similar to that of ANP. Like ANP, BNP induces a vasorelaxation that is independent of endothelium and is associated with very sustained increases in cyclic GMP, but not cyclic AMP, levels in rat thoracic aorta. The BNP-induced cyclic GMP elevation, like the vasorelaxation, is also independent of endothelium and is not blocked by methylene blue (10 microM), a soluble guanylate cyclase inhibitor. Furthermore, BNP-induced cyclic GMP elevation is independent of extracellular calcium and potentiated by the cyclic GMP-phosphodiesterase inhibitor M & B 22948. Therefore, the pharmacological characteristics of BNP in rat blood vessels are very similar to those of ANP, suggesting that BNP and ANP may act through a common receptor and post-receptor mechanism to cause vasodilation.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1989

[Effect of tolmetin on responsiveness of isolated guinea pig tracheal smooth muscles].

Tolmetin directly relaxed the isolated guinea pig tracheal smooth muscles, increased the muscle responsiveness to histamine or carbachol and enhanced the tracheal Schultz-Dale reaction. Prostaglandin E2 synthesized by cyclooxygenase was transformed into prostaglandin B2 (PGB2) with alkali, PGB2 and the lipoxygenase metabolite leukotriene B4 (LTB4) were measured by high-performance liquid chromatography, whereas slow-reacting substance of allergy (SRS-A) was determined by bioassay. Tolmetin showed inhibitory effects on prostaglandin E2 synthesis, with the IC50 being 30 mumol/L, but no effect on LTB4 synthesis (up to 100 mumol/L). SRS-A release was potentiated by tolmetin at 10 and 50 mumol/L. The effects of tolmetin on arachidonic acid metabolism may be responsible for its effects on tracheal smooth muscles. It is suggested that asthma attacks may be induced or enhanced by tolmetin in patients with asthma.

Animals↗
PubMed1989

[Effects of tetrandrine on cytoplasmic free calcium in rat neutrophils].

Neutrophils (NP) cytoplasmic free Ca2+ concentrations ([Ca2+]i) under several conditions were measured with Quin 2 in rats. The process of loading Quin 2-AM into the cells followed by its hydrolysis was assured by monitoring the shift of fluorescent emission spectrum of Quin 2-AM to that of Quin 2. The resting [Ca2+]i of NP in Ca2(+)-containing and Ca2(+)-free solutions were 186 +/- 45 and 46 +/- 16 nmol/L, respectively, indicating extracellular calcium concentration ([Ca2+]0) plays an important role on [Ca2+]i. Among agents tested, prostaglandin E2 (PGE2) 100 nmol/L did not change [Ca2+]i significantly. Calcimycin 25 mumol/L, leukotriene B4(LTB4) 60 nmol/L and platelet activating factor (PAF) 10 nmol/L increased [Ca2+]i of NP in Ca2(+)-containing solution from 185 +/- 54, 175 +/- 36 and 188 +/- 54 to 814 +/- 67, 577 +/- 229 and 540 +/- 174 nmol/L, respectively. But, compound 48/80 3.2 micrograms/ml, LTB4 300 nmol/L, PAF 10 nmol/L and PAF 5 nmol/L plus LTB4 150 nmol/L did not change significantly [Ca2+]i of NP in Ca2(+)-free solution, indicating that these agonists can not release intracellularly stored Ca2+ or no stored Ca2+ in NP is available. The rises of [Ca2+]i produced by calcimycin, PAF and LTB4 were markedly inhibited by tetrandrine (Tet) 65 mumol/L. These results, as a whole, show that Tet inhibits the rises of [Ca2+]i of NP induced by calcimycin, PAF and LTB4 via decreasing Ca2+ influx. The Ca2+ antagonism in this case may be related to its anti-allergic actions.

Alkaloids↗