Protein kinase C mediates angiotensin II-induced contractions and the release of endothelin and prostacyclin in rat aortic rings
| Autor: | G.K. Oriji, Harry R. Keiser |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Endothelin Receptor Antagonists
Male medicine.medical_specialty Vascular smooth muscle Clinical Biochemistry Aorta Thoracic Prostacyclin Naphthalenes Peptides Cyclic Muscle Smooth Vascular chemistry.chemical_compound 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine Internal medicine medicine Animals Vasoconstrictor Agents Staurosporine Enzyme Inhibitors Phorbol 12 13-Dibutyrate Protein Kinase C Protein kinase C Dose-Response Relationship Drug Chemistry Angiotensin II Endothelins Osmolar Concentration Cell Biology Epoprostenol Rats Calphostin C Endocrinology cardiovascular system medicine.symptom Endothelin receptor Muscle Contraction medicine.drug Muscle contraction |
| Zdroj: | Prostaglandins, Leukotrienes and Essential Fatty Acids. 57:135-141 |
| ISSN: | 0952-3278 |
| Popis: | Angiotensin II (Ang II) stimulation of vascular smooth muscle results in a myriad of intracellular signals that interact to produce the final physiologic response of the cell. We used rat aortic rings to investigate the role of protein kinase C (PKC) in Ang II-induced contractions and in the concomitant release of endothelin (ET) and prostacyclin (PGI2). Ang II (10(-9) M) produced a rapid contraction which was sustained for 10 min. When aortic rings were pretreated with graded concentrations of each of the four different inhibitors of PKC, that is, (i) 1-(5-isoquinolinesulfonylmethyl) piperazine (H7); (ii) 1-(5-isoquinolinesulfonyl) piperazine(CL); (iii) staurosporine; or (iv) calphostin C, inhibition of Ang II-induced contractions began at 10(-9) M, and was nearly complete at 10(-6) M. Ang II-induced contractions were associated with a 10-fold increase in the release of both ET and PGI2. Pretreatment with 10(-6) M of any one of the same four PKC inhibitors blocked Ang II-induced release of both ET and PGI2. Pretreatment with a blocker of the endothelin-A receptor, BQ123 (10(-6) M), inhibited, by approximately 50%, Ang II-induced contractions, and the release of both ET and PGI2. In aortic rings denuded of endothelium, Ang II-induced contractions, and the release of both ET and PGI2 were significantly reduced, compared to intact rings. We conclude that PKC mediates Ang II-induced contractions in rat aortic rings and that the secondary release of both ET and PGI2 during Ang II-induced contractions is mediated, at least in part, by PKC. In addition, approximately half of Ang II-induced contractile force and of PGI2 release is dependent upon the ET released from endothelial cells. |
| Databáze: | OpenAIRE |
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