Role of protein kinases in mediating diabetes-induced augmented vasoconstriction to endothelin-1 in the renal arteries of STZ-diabetic rats.
Diabetes is associated with increased reactivity of the renal vascular bed to endothelin-1 (ET-1). It has been observed that diabetes is associated with over-expression of ET(A)- and ET(B)-receptors in the rat renal cortex. However it is not known if these receptors are over-expressed in the renal artery. The objectives of this study were to determine changes in ET-1 receptors and signalling pathways in diabetic renal arteries, to determine the relative roles of protein kinase C and tyrosine kinase activation in mediating these responses and to investigate the role of Rho-kinase activity in mediating the vasoconstrictor responses to ET-1. This study was performed on isolated renal artery segments obtained from STZ-diabetic rats. Results from this study showed that the vasoconstrictor response to ET-1 was potentiated in the diabetic renal artery segments compared to the control animals. Using selective ET-1 receptor antagonists, BQ123 and BQ788, the enhanced ET-1-induced vasoconstriction was shown in this study not to be related to changes in receptor affiinity or receptor subtype distribution. However, the augmented vasoconstrictor response to ET-1 in the diabetic renal artery preparations may be related to increased influx of Ca(2+) through L-type channels and also to increased tyrosine kinase activity.
Yousif
Mariam H M
MH
Department of Pharmacology & Toxicology, Faculty of Medicine, Kuwait University, Safat, Kuwait. mariam@hsc.edu.kw
D000577:Amides / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000503:physiopathology*; D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D019833:Genistein / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044022:Receptor, Endothelin A / Q000378:metabolism; D012077:Renal Artery / Q000187:drug effects / Q000201:enzymology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D019311:Staurosporine / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology; D054460:rho-Associated Kinases
D000577:Amides; D020746:Calcium Channels, L-Type; D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D044022:Receptor, Endothelin A; D014665:Vasodilator Agents; C108830:Y 27632; D019833:Genistein; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D011493:Protein Kinase C; D019311:Staurosporine; D009543:Nifedipine; D002118:Calcium