Enhanced renal expression of preproendothelin mRNA during chronic angiotensin II hypertension.
The purpose of this study was to determine the role of endothelin in mediating the renal hemodynamic and arterial pressure changes observed during chronic ANG II-induced hypertension. ANG II (50 ng x kg(-1) x min(-1)) was chronically infused into the jugular vein by miniosmotic pump for 2 wk in male Sprague-Dawley rats with and without endothelin type A (ET(A))-receptor antagonist ABT-627 (5 mg x kg(-1) x day(-1)) pretreatment. Arterial pressure increased in ANG II rats compared with control rats (149 +/- 5 vs. 121 +/- 6 mmHg, P < 0.05, respectively). Renal expression of preproendothelin mRNA was increased by approximately 50% in both the medulla and cortex of ANG II rats. The hypertensive effect of ANG II was completely abolished in rats pretreated with the ET(A)-receptor antagonist (114 +/- 5 mmHg, P < 0.05). Glomerular filtration rate was decreased by 33% in ANG II rats, and this response was attenuated in rats pretreated with ET(A)-receptor antagonist. These data indicate that activation of the renal endothelin system by ANG II may play an important role in mediating chronic renal and hypertensive actions of ANG II.
Alexander
B T
BT
Department of Physiology and Biophysics, Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson, Mississippi 39216, USA.
Cockrell
K L
KL
Rinewalt
A N
AN
Herrington
J N
JN
Granger
J P
JP
D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000077868:Atrasentan; D001794:Blood Pressure / Q000187:drug effects*; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D016232:Endothelins / Q000235:genetics*; D005786:Gene Expression Regulation / Q000502:physiology*; D005919:Glomerular Filtration Rate; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D007262:Infusions, Intravenous; D007668:Kidney / Q000378:metabolism* / Q000503:physiopathology; D007672:Kidney Cortex / Q000378:metabolism; D007679:Kidney Medulla / Q000378:metabolism; D008297:Male; D011498:Protein Precursors / Q000235:genetics*; D011759:Pyrrolidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology; D014158:Transcription, Genetic / Q000502:physiology*; D014563:Urodynamics / Q000187:drug effects / Q000502:physiology
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D016232:Endothelins; D011498:Protein Precursors; D011759:Pyrrolidines; D012333:RNA, Messenger; D044022:Receptor, Endothelin A; D000804:Angiotensin II; D000077868:Atrasentan