| Ca(2+)-insensitive vascular protein kinase C during pregnancy and NOS inhibition. | |
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MedLine Citation:
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PMID: 10523386 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Pregnancy-induced hypertension is associated with increased vascular resistance; however, the cellular mechanisms involved are unclear. We have previously found that the relation between Ca(2+) entry and the developed force in vascular smooth muscle is altered during normal pregnancy and in a rat model of pregnancy-induced hypertension produced by long-term treatment with the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME). The purpose of this study was to investigate whether the pregnancy-associated changes in the vascular Ca(2+) entry-force relation reflect changes in the amount and/or activity of Ca(2+)-insensitive protein kinase C (PKC) isoforms. Active stress and the amount and activity of PKC were measured in deendothelialized aortic strips from nonpregnant and pregnant rats untreated or treated with L-NAME and incubated in Ca(2+)-free (2 mmol/L EGTA) Krebs solution. In nonpregnant rats, the PKC activator phorbol 12,13-dibutyrate (PDBu, 10(-6) mol/L) and the alpha-adrenergic agonist phenylephrine (Phe, 10(-5) mol/L) caused significant, maintained increases in active stress and PKC activity that were inhibited by the PKC inhibitors staurosporine and calphostin C. Western blots in aortic strips of nonpregnant rats revealed the Ca(2+)-insensitive delta-PKC and zeta-PKC isoforms. Both PDBu and Phe caused translocation of delta-PKC from the cytosolic to the particulate fraction. Compared with nonpregnant rats, the amount of delta-PKC and zeta-PKC and the PDBu-stimulated and Phe-stimulated stress, PKC activity and translocation of delta-PKC were significantly reduced in late pregnant rats but significantly enhanced in pregnant rats treated with L-NAME. The PDBu-induced and Phe-induced responses in nonpregnant rats treated with L-NAME were not significantly different from nonpregnant rats, whereas the responses in pregnant rats treated with L-NAME+L-arginine were not significantly different from pregnant rats. These results provide evidence that a signaling pathway in vascular smooth muscle possibly involving the Ca(2+)-insensitive delta-PKC and zeta-PKC isoforms is reduced in late pregnancy and enhanced during long-term inhibition of nitric oxide synthesis. The changes in the amount and activity of vascular PKC isoforms may, in part, explain the changes in vascular resistance during normal pregnancy and pregnancy-induced hypertension. |
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Authors:
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C A Kanashiro; B T Alexander; J P Granger; R A Khalil |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Hypertension Volume: 34 ISSN: 0194-911X ISO Abbreviation: Hypertension Publication Date: 1999 Oct |
Date Detail:
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Created Date: 1999-11-09 Completed Date: 1999-11-09 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 7906255 Medline TA: Hypertension Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 924-30 Citation Subset: IM |
Affiliation:
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Department of Physiology and Biophysics and the Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson 39216-4505, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Calcium / metabolism* Enzyme Inhibitors / pharmacology Female Hypertension / etiology, metabolism*, physiopathology* NG-Nitroarginine Methyl Ester / pharmacology Naphthalenes / pharmacology Nitric Oxide / metabolism Nitric Oxide Synthase / antagonists & inhibitors* Pregnancy Pregnancy Complications, Cardiovascular / metabolism, physiopathology Pregnancy, Animal / physiology* Protein Kinase C / metabolism* Rats Rats, Sprague-Dawley Staurosporine / pharmacology Vascular Resistance* / drug effects |
| Grant Support | |
ID/Acronym/Agency:
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HL-51971/HL/NHLBI NIH HHS; HL-52696/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Enzyme Inhibitors; 0/Naphthalenes; 10102-43-9/Nitric Oxide; 121263-19-2/calphostin C; 50903-99-6/NG-Nitroarginine Methyl Ester; 62996-74-1/Staurosporine; 7440-70-2/Calcium; EC 1.14.13.39/Nitric Oxide Synthase; EC 2.7.11.13/Protein Kinase C |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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