Reversal of angiotensin II effect on the cyclic adenosine 3',5' monophosphate response to isoprenaline in cardiac hypertrophy.
OBJECTIVE
The aim was to examine the effect of angiotensin II on the response of hypertrophic cardiac myocytes to the beta adrenergic receptor agonist isoprenaline.


METHODS
Viable ventricular myocytes were isolated from hypertrophic hearts of Dahl S rats and hearts of Dahl R rats. Myocytes were stimulated with isoprenaline. cAMP content was measured by competitive binding radioimmunoassay.


RESULTS
Hypertrophic Dahl S myocytes had smaller cAMP response to isoprenaline than Dahl R myocytes (p less than 0.05). Angiotensin II inhibited cAMP stimulation in Dahl R myocytes. In contrast, angiotensin II increased cAMP accumulation in hypertrophic Dahl S myocytes compared to the effect of isoprenaline alone (p less than 0.05). Enhancement of isoprenaline stimulation of cAMP accumulation by angiotensin II was positively related to the degree of cardiac hypertrophy. Angiotensin II treatment in the absence of isoprenaline had no effect on cAMP levels.


CONCLUSIONS
The reversal of the normal inhibitory action of angiotensin II is evidence of a unique alteration in the signal transduction of beta receptor stimulation and is of potential importance in defining the role of angiotensin II in cardiac hypertrophy.
Sunga
P S
PS
Department of Medicine, University Hospital Research Centre, University of British Columbia, Vancouver, Canada.
Rabkin
S W
SW
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D006332:Cardiomegaly / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis*; D006321:Heart / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D013268:Stimulation, Chemical
D000804:Angiotensin II; D000242:Cyclic AMP; D007545:Isoproterenol