title: Adenylate cyclase activity during development and reversal of cardiac hypertrophy.
abstract: Inotropic responses to isoproterenol of hypertrophied hearts have been shown to be decreased. We have previously reported that in 13-week-old spontaneously hypertensive rats (SHR) this decrease is probably due to decreased beta-adrenergic receptor number, while in hearts from two kidney-one clip renal hypertensive rats (2K-1C RHR), this is due to a decreased nucleotide regulatory protein activity. We now show that changes in 2K-1C RHR are time dependent. One week after instituting development of hypertension the heart is already hypertrophied. Biochemical changes consistent with decreased glucagon receptors are seen, as well as beginning changes consistent with decreases in the nucleotide regulatory protein activity. By two weeks this is more evident. Hypertrophy and biochemical changes can be reversed up to six weeks, but by ten weeks the activity of the catalytic subunit of the adenylate cyclase system is decreased. In 1K-1C RHR, biochemical changes in the cyclase system are accelerated as compared with the 2K-1C model. In SHR, changes in 24-week-old rats are the same as in the 13-week-old rats. It is concluded that in cardiac hypertrophy associated with different models of hypertension the decreased inotropic responsiveness to isoproterenol is associated with different biochemical defects in the beta-adrenergic receptor response coupling pathway, and that reversal in function occurs only when there is no apparent change in the catalytic subunit of the adenylate cyclase complex.
authors.forename: K
authors.initials: K
authors.lastname: Kumano
authors.forename: P A
authors.initials: PA
authors.lastname: Khairallah
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure; D006332:Cardiomegaly / Q000201:enzymology*; D006973:Hypertension / Q000201:enzymology*; D008297:Male; D009206:Myocardium / Q000201:enzymology; D009392:Nephrectomy; D051381:Rats; D013997:Time Factors
chemical_list: D000262:Adenylyl Cyclases