Endothelin ETA receptor antagonism does not attenuate angiotensin II-induced cardiac hypertrophy in vivo in rats.
1. Angiotensin (Ang) II causes cardiac hypertrophy in vitro and in vivo. It also stimulates the release of endothelin (ET)-1. Endothelin-1 induces hypertrophy of cardiomyocytes in vitro. 2. In the present study, we examined whether the cardiac hypertrophic action of AngII in vivo was mediated by ET-1 via ETA receptors. We also determined whether arginine vasopressin (AVP), another ET-1 stimulator, could cause cardiac hypertrophy in vivo through an ET-1-dependent pathway. 3. In Sprague-Dawley rats (n = 8 per group), we determined whether the orally administered ETA receptor antagonist BMS 193884 could attenuate the cardiac hypertrophic effect of: (i) i.v. AngII infusion at either 100 or 200 ng/kg per min, i.v., for 1 week; (ii) AngII infusion at 100 ng/kg per min, i.v., for 2 weeks; and (iii) AVP infusion at either 2 or 10 ng/kg per min, i.v., for 1 week. Mean arterial pressure and heart rate were also measured. 4. Infusion with AngII for both 1 and 2 weeks increased left ventricular weight. Only AngII infusion at 200 ng/kg per min for 1 week increased blood pressure. Endothelin ETA receptor blockade did not attenuate the left ventricular hypertrophy, even though it reduced the hypertensive effect of AngII. Arginine vasopressin increased blood pressure, but did not cause cardiac hypertrophy. 5. We showed that AngII can cause cardiac hypertrophy through a direct, blood pressure-independent effect on the heart. Endothelin-1 did not mediate the cardiac hypertrophic effect of AngII through ETA receptors. This may indicate the involvement of ETB receptors in this model of cardiac hypertrophy. Arginine vasopressin did not cause cardiac hypertrophy in vivo.
De Smet
H R
HR
Department of Medicine, Flinders University of South Australia, Bedford Park, Australia.
Menadue
M F
MF
Oliver
J R
JR
Phillips
P A
PA
D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D006332:Cardiomegaly / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1 / Q000502:physiology*; D006352:Heart Ventricles / Q000187:drug effects; D007262:Infusions, Intravenous; D008297:Male; D010080:Oxazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000097:blood; D013449:Sulfonamides / Q000494:pharmacology
C412823:BMS 193884; D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1; D010080:Oxazoles; D013449:Sulfonamides; D000804:Angiotensin II; D001127:Arginine Vasopressin; D000450:Aldosterone; D012083:Renin