Comparison of angiotensin II type-1 and type-2 receptor antagonists on angiotensin II-induced IP3 generation in cardiomyocytes.
1. Angiotensin II (ang II) produced significant (P<0.01) increases of inositol 1,4,5-mono-, -di- and -triphosphates (IP1, IP2 and IP3) within 1 min of treatment of cardiomyocytes prepared as primary culture from 7-day-old chick embryo hearts. 2. The ang II receptor type 1 (AT1-R) antagonist losartan blocked ang II-stimulated production of IP3; however, the inhibition was not complete even at 10(-5) M. 3. The ang II receptor type 2 (AT2-R) antagonist PD123319 blocked ang II-induced IP3 production but to a lesser extent than losartan. At 10(-5) M, losartan reduced ang II-induced formation of IP3 by 71%, whereas PD123319 reduced IP3 formation by ang II by 40%. 4. Neither losartan nor PD123319, 10(-5) M, affected IP3 formation in cardiomyocytes that were not treated by ang II. 5. The combination of both antagonists, at concentrations that each partly reduced IP3, completely inhibited IP3 formation. Thus AT1 and AT2 receptor blockade may be necessary to completely block the effects of ang II mediated by the IP3 signal transduction pathway.
Goutsouliak
V
V
Department of Medicine, University of British Columbia, Vancouver, Canada.
Rabkin
S W
SW
D000804:Angiotensin II / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D002642:Chick Embryo; D006321:Heart / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology*; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis*; D019808:Losartan / Q000494:pharmacology*; D009206:Myocardium / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology*; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2
D057911:Angiotensin Receptor Antagonists; D007093:Imidazoles; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II; C073402:PD 123319; D015544:Inositol 1,4,5-Trisphosphate; D019808:Losartan