Tyrosine kinase receptor alteration of renal vasoconstriction in rats is sex- and age-related.
Male rat renal blood vessels undergo reduced contraction to norepinephrine with aging. There is a greater renal vascular impairment in male compared with female rats. We investigated specific tyrosine kinase receptor inhibition of renal interlobar artery responsiveness to phenylephrine in male and female rats at specifically designated ages. Vessels from young male rats contracted much less to phenylephrine when the vessels were pretreated with the tyrosine kinase inhibitors Lavendustin A, HNMPA-(AM)₃, or AG1478. Vessels from adult female rats pretreated with Lavendustin A showed no difference in contraction from control, but did demonstrate a slightly reduced contraction when pretreated with AG1478. Middle-aged male rat vessels treated with Lavendustin A demonstrated no inhibition, but the insulin and epidermal growth factor receptor (EGFR) antagonists both induced a decline in contraction. Vessels from aged male rats demonstrated no effect related to the 3 pretreatments. Middle-aged and aged female rats pretreated with any inhibitor demonstrated no inhibitor-dependent alterations. We conclude that maximum contraction of interlobar arteries from adult male rats is reduced when tyrosine kinase receptor activity is reduced. Female rats demonstrated much less inhibitor-related change of contraction.
Department of Physiology and Biophysics, Health Sciences Center, University of Louisville School of Medicine, 500 South Preston St., Louisville, KY 409292, USA. jcpass01@gwise.louisville.edu
John C
JC
Passmore
John T
JT
Fleming
Suresh C
SC
Tyagi
Jeff C
JC
Falcone
D000375:Aging; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009994:Osmolar Concentration; D010656:Phenylephrine / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011972:Receptor, Insulin / Q000037:antagonists & inhibitors; D012079:Renal Circulation / Q000187:drug effects; D012727:Sex Characteristics; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D004791:Enzyme Inhibitors; D047428:Protein Kinase Inhibitors; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D011972:Receptor, Insulin; D017027:Protein Tyrosine Phosphatases