Drugs online research references
Zhongguo Yao Li Xue Bao. 1993 Jan;14(1):21-6.
Cyclopiazonic acid causes endothelium-dependent relaxation in rat aorta.
Zheng XF, Guan YY, Kwan CY.
Department of Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
The effects of cyclopiazonic acid (CPA), a selective inhibitor of Ca(2+)-pump ATPase for endoplasmic reticulum (ER), on the contractility of rat aorta with and without intact endothelium were studied to investigate the possible involvement of endothelial ER Ca(2+)-pump in the release of endothelium-derived relaxing factor (EDRF), which is known to cause vascular relaxation or inhibition of phenylephrine (PE)-precontracted aorta. When added to the organ bath cumulatively, CPA concentration-dependently caused gradual development of contraction, which was much less in aortic rings with intact endothelium than in endothelium-denuded aortic rings. But CPA at low concentrations (1-3 mumol.L-1) induced vascular relaxation when added to PE (3 mumol.L-1)-precontracted aortic rings with intact endothelium, but not in denuded aortic rings. This relaxant effect of CPA is very similar to the effect of acetylcholine (ACh), which is well recognized to be mediated by the release of EDRF from the endothelium. NG-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, completely prevented the vascular relaxation induced by CPA or ACh and the inhibitory effect of L-NAME was partially reversed by L-arginine (L-Arg). Treatment of the aortic rings with nifedipine (Nif) 0.3 mumol.L-1 did not affect the relaxant effect of ACh or CPA on PE-induced contraction indicating that the Ca(2+)-entry to the endothelial cells as a result of receptor activation by ACh or ER Ca(2+)-pump inhibition by CPA was via channels other than L-type Ca2+ channels.(ABSTRACT TRUNCATED AT 250 WORDS)
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8503281&dopt=Abstract
Br J Pharmacol. 1996 Mar;117(6):1035-40.
Evidence for mediation by endothelium-derived hyperpolarizing factor of relaxation to bradykinin in the bovine isolated coronary artery independently of voltage-operated Ca2+ channels.
Drummond GR, Cocks TM.
Department of Pharmacology, University of Melbourne, Victoria, Australia.
1. The role of endothelium-derived hyperpolarizing factor and voltage-operated Ca2+ channels in mediating endothelium-dependent, NG-nitro-L-arginine (L-NOARG; 100 microM) -resistant relaxations to bradykinin (BK), was examined in isolated rings of endothelium-intact bovine left anterior descending coronary artery. 2. Rings of artery were contracted isometrically to approximately 40% or their respective maximum contraction to 125 mM KCl Krebs solution (KPSSmax) with the thromboxane A2-mimetic, U46619. Relaxations to BK and the endothelium-independent NO donor, S-nitroso-N-acetylpenicillamine (SNAP), were normalized as percentages of reversal of the initial contraction to U46619. All experiments were carried out in the presence of indomethacin (3 microM). 3. BK caused concentration-dependent relaxations [sensitivity (pEC50) 9.88 +/- 0.05; maximum relaxation (Rmax), 103.3 +/- 0.5%] in U46619-contracted rings of bovine coronary artery. L-NOARG (100 microM) caused a significant (P < 0.01) 3 fold reduction in the sensitivity to BK (pEC50, 9.27 +/- 0.11) without affecting the Rmax (101.8 +/- 2.3%). A similar, significant 3 fold reduction in sensitivity to BK with no change in Rmax was observed after treatment with oxyhaemoglobin (20 microM; pEC50, 9.18 +/- 0.13, P < 0.001) or a combination of oxyhaemoglobin (20 microM) and L-NOARG (100 microM; pEC50, 9.08 +/- 0.10, P < 0.001). Oxyhaemoglobin (20 microM) either alone or in combination with L-NOARG (100 microM) caused an approximate 600 fold decrease in the sensitivity to SNAP. 4. The L-type voltage-operated Ca2+ channel inhibitor, nifedipine (0.3 microM-3 microM), reduced the maximum contraction (Fmax) to isotonic 68 mM KCl Krebs solution (103.5 +/- 2.0% KPSSmax) by 85-90% (P < 0.001); yet, the highest concentration of nifedipine (3 microM) caused only a small but significant reduction in both the sensitivity and Fmax to U46619. By contrast, nifedipine (3 microM) had no effect on the relaxation response to BK. Furthermore, a combination of nifedipine (3 microM) and L-NOARG (100 microM) had no further inhibitory effects on relaxations to BK (pEC50, 8.79 +/- 0.10; Rmax, 101.7 +/- 2.4%) than did L-NOARG (100 microM) alone (pEC50, 9.05 +/- 0.12; Rmax, 99.62 +/- 1.19). Also, nifedipine (0.3 microM and 3 microM) had no effect on the maximum relaxation to the K+ channel opener, levcromakalim (0.3 microM). 5. In the presence of nifedipine (0.3 microM to control contractions induced by high KCl) and isotonic 68 mM KCl Krebs solution (to inhibit K+ channel activity), relaxations to BK (pEC50, 9.42 +/- 0.10; Rmax, 93.9 +/- 1.8%) were similar to those observed in normal Krebs solution (pEC50, 9.58 +/- 0.09; Rmax, 98.4 +/- 0.8%). However, in the presence of 68 mM KCl Krebs solution the inhibitory effect of L-NOARG (100 microM) on relaxations to BK (pEC50, 8.53 +/- 0.20; Rmax, 31.0 +/- 11.3%) was markedly greater than that in normal KCl Krebs solution (pEC50, 9.12 +/- 0.08; Rmax, 91.5 +/- 2.0%). Similar treatment with 68 mM KCl Krebs had no effect on relaxations to the NO donor, SNAP, yet abolished the response to the K+ channel opener, levcromakalim (0.3 microM). 6. In summary, this study has shown that (1) NO synthesis in response to BK in bovine coronary artery endothelial cells in situ is likely to be abolished by L-NOARG, (2) NO-independent relaxations to BK are markedly attenuated by 68 mM KCl-containing Krebs, which, in the absence of L-NOARG, had no effect, (3) nifedipine blocked contractions to a maximum-depolarizing stimulus (KCl) yet had no effect on NO-independent relaxations to BK, and (4) maximum relaxations to levcromakalim were abolished by 68 mM KCl Krebs but were not affected by nifedipine. Therefore, we hypothesize that if smooth muscle hyperpolarization is involved in non-NO-, endothelium-dependent relaxation in bovine coronary arteries contracted with U46619, then it can accomplish this via a mechanism which does not i
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8882593&dopt=Abstract
Eur J Endocrinol. 1997 Jan;136(1):121-2.
The stimulatory effect of endothelin-1 on regenerating adrenal cortex is reversed by nifedipine.
Zieleniewski W.
Institute of Endocrinology, Lodz, Poland.
Endothelin-1 (ET-1), a potent vasoconstrictor, was found to act in non-vascular tissues, for example it enhanced aldosterone output from adrenal zona glomerulosa. As the adrenal cortex is capable of regeneration after enucleation, it seemed of interest to study the effects of ET-1 on adrenocortical regeneration. The study was performed on adult rats subjected to left adrenal enucleation combined with contralateral adrenalectomy. Mitotic index was employed to assess the proliferation of regenerating adrenal cortex cells. Plasma corticosterone was measured by a standard RIA kit. ET-1 significantly raised the mitotic index of regenerating rat adrenal cortex by six days after surgery. On the other hand, nifedipine reduced the proliferation ratio and abolished the stimulatory influence of ET-1. Similarly, ET-1 enhanced corticosterone output from the regenerating adrenal cortex, and this could be prevented by the addition of nifedipine. This study has shown that ET-1 might act as a regulatory factor on the regenerating adrenal cortex via calcium channels.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9037138&dopt=Abstract
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