Gender related alterations of β-adrenoceptor mechanisms in heart failure due to arteriovenous fistula.
This study was undertaken to determine gender related changes in different components of β-adrenoceptor (β-AR) system in response to arteriovenous fistula (AV-shunt), which is known to produce heart failure due to volume overload. AV-shunt was induced in male and female rats for 16 weeks by the needle technique; ovariectomized (OVX) rats treated with or without estrogen were also used. Although AV-shunt for 16 weeks produced cardiac hypertrophy in both sexes, male animals showed cardiac dysfunction whereas cardiac performance was maintained in females. Both β(1) -AR and β(2) -AR protein content and mRNA levels were decreased in male and increased in female hearts post-AV-shunt. The basal adenylyl cyclase (AC) activity was lower in the female heart; however, AC protein content and the increase in epinephrine (EPi)-stimulated AC activity were greater in the female AV-shunt group as compared to males. While AC V/VI and β-arrestin 2 mRNA levels were decreased in males, mRNA level for GRK2 was increased in females post-AV-shunt. In contrast to intact females, AV-shunt OVX animals showed depressed cardiac function, decreased β(1) -AR, β(2) -AR, and AC protein content, as well as reduced EPi-stimulated AC activity. Treatment of OVX rats with 17-β estradiol attenuated the AV-shunt induced changes in β-AR and AC protein content as well as cardiac dysfunction. These results reveal that β-AR signal transduction system in response to AV-shunt is downregulated in males and upregulated in females. Furthermore, estrogen appears to play an important role in the upregulation of β-AR mechanisms and the maintenance of cardiac function in AV-shunt females.
Faculty of Medicine, Department of Physiology, University of Manitoba, Institute of Cardiovascular Sciences, St. Boniface Hospital Research, Winnipeg, Canada.
Melissa R
MR
Dent
Paramjit S
PS
Tappia
Naranjan S
NS
Dhalla
D000262:Adenylyl Cyclases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001164:Arteriovenous Fistula; D004195:Disease Models, Animal; D004837:Epinephrine / Q000494:pharmacology; D004958:Estradiol / Q000008:administration & dosage; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006333:Heart Failure / Q000378:metabolism*; D006352:Heart Ventricles / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics / Q000378:metabolism*; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics / Q000378:metabolism*; D012737:Sex Factors; D015398:Signal Transduction
D012333:RNA, Messenger; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D004958:Estradiol; D000262:Adenylyl Cyclases; D004837:Epinephrine