Angiotensin II receptor subtypes in the skeletal muscle vasculature of patients with severe congestive heart failure.
BACKGROUND
Vascular remodeling occurs in the skeletal muscle of patients with severe congestive heart failure (CHF); this remodeling is mediated in part by increased activity of the renin-angiotensin system. Animal models suggest that in the vasculature, angiotensin II receptor type 2 (AT2-R) expression may be upregulated in pathological states associated with vascular remodeling. The therapeutic effects of an AT1-R antagonist may, therefore, be in part due to increased plasma angiotensin II levels, which stimulate AT2-R. However, whether AT2-R is expressed in the skeletal muscle vasculature of patients with severe CHF is unknown.


RESULTS
The steady-state transcript levels of the AT1-R and AT2-R genes were analyzed by reverse transcription-polymerase chain reaction in RNA samples prepared from the skeletal muscle of 12 patients with severe CHF (f1.gif" BORDER="0">O(2)<10 mL. kg(-1). min(-1)) and 5 age-matched healthy subjects who underwent vastus lateralis biopsies. Human fetal skeletal muscle RNA served as a positive control for the expression of AT1-R and AT2-R gene transcripts. Transcripts from the AT1-R gene were detected readily in all samples. In contrast, transcripts from the AT2-R gene were only detected in fetal skeletal muscle samples and could not be detected in the skeletal muscle vasculature of healthy subjects or that of CHF patients, who were treated with either angiotensin-converting enzyme inhibitors or AT1-R antagonists.


CONCLUSIONS
The AT2-R gene is not expressed in the skeletal muscle of patients with CHF. In the absence of detectable AT2-R gene transcripts, the AT2-R pathway is unlikely to contribute to the effects of AT1-R antagonists on the skeletal muscle vasculature in patients with severe CHF.
Malendowicz
S L
SL
Department of Medicine, Division of Cardiology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Ennezat
P V
PV
Testa
M
M
Murray
L
L
Sonnenblick
E H
EH
Evans
T
T
LeJemtel
T H
TH
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D001706:Biopsy; D001808:Blood Vessels / Q000196:embryology / Q000378:metabolism*; D005260:Female; D005333:Fetus; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000032:analysis / Q000235:genetics; D006333:Heart Failure / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000098:blood supply / Q000196:embryology / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D014841:von Willebrand Factor / Q000032:analysis / Q000235:genetics
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D014841:von Willebrand Factor; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases