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Molecular Pharmacology, Vol 14, 468-477, Copyright © 1978 by the American Society for Pharmacology and Experimental Therapeutics

Calcium Fluxes, Calcium Binding, and Adenosine Cyclic 3',5'-Monophosphate-Dependent Protein Kinase Activity in the Aorta of Spontaneously Hypertensive and Kyoto Wistar Normotensive Rats

R. C. BHALLA 1, R. C. WEBB 1, D. SINGH 1, T. ASHLEY 1, and T. BROCK 1

1 Department of Anatomy and Cardiovascular Center, University of Iowa, Iowa City, Iowa 52242

Spontaneously hypertensive rats and Kyoto Wistar normotensive rats were compared with respect to calcium fluxes in aortic strips, membrane phosphorylation and calcium uptake by microsomes, and cyclic AMP-dependent protein kinase activity in tissue extracts of aorta. The aortic strips of hypertensive rats accumulated more 45Ca than those of normotensive animals. The calcium content of the aorta increased with age of the animals from 30 days to 1 year and was consistently higher in hypertensive than in normotensive rats. Calcium uptake by the aortic microsomes was significantly decreased in hypertensive (p < 0.05) compared with normotensive rats in the presence and absence of 1 µM cyclic AMP, as was cyclic AMP-dependent phosphorylation of microsomes. Cyclic AMP-dependent and -independent protein kinase activity in the 27,000 x g supernatant of the aortas of 12-16-week-old hypertensive rats was reduced by 42% and 34%, respectively, using histone as a substrate. Differences both in calcium uptake by microsomes treated with cyclic AMP and in cyclic AMP-dependent protein kinase activity in the tissue extracts were evident at 30 days of age. These observations reflect the importance of impaired membrane phosphorylation in the pathogenesis of hypertension.

Submitted on October 25, 1977
Accepted on January 9, 1978




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