RNA synthesis and RNA polymerase activity during natural cardiac hypertrophy

RNA SYNTHESIS AND RNA POLYMERASE ACTIVITY DURING NATURAL CARDIAC HYPERTROPHY. Paul B. Taylor and Jim D. McCully. Department of Biology, _-ll-___---__l__-_-------University of Windsor, Windsor, Ontario N9B 3P4. Alterations in RNA synthesis and RNA polymerase activity during cardiac hypertrophy was investigated using a natural growth model. Hearts from male Wistar rats (21, 50 and 100 days of age) were used and represented a 7-fold change in tissue mass. RNA synthesis was determined by perfusing isolated hearts for 60 min. at 37OC with a Krebs-Henseleit buffer containing 15 mM glucose and r3HIuridine (0.1 yCi/ml; 51.0 Ci/m mol). Uridine incorporation corrected for alterations in the specific activity of the cytoplasmic uridine nucleotide pool, decreased 5-fold from 21 to 50 days of age and 4-fold from 50 to 100 days (P<.Oi). RNA polymerase activity in isolated nuclei from total tissue samples decreased 2-fold from 21 to 50 days of age with no further change from 50 to 100 The enzyme activity in myocyte nuclei did not change days. with age. However, in the non-myocytes, RNA polymerase activity decreased with increasing age. These data indicate that with increasing age and tissue growth the large reduction in myocardial RNA synthesis is only partially accounted for by changes in RNA polymerase activity and possibly factors that influence the DNA capacity for RNA synthesis may be an important regulatory site during this form of muscle growth. Supported by the Ontario Heart Foundation (12-4) and NSERC (A7330).

Na+

INFLUX AND BEAT-DEPEMDEMT ACTKI~B. Kyosuke Tennma, Tai Akera and of Pharmacology and Toxicology, Michigan

ONSET OF OUABAIN Theodore M. Rrody. Dept. State Univ., East Lansing.

Effects of stimulation frecluency on Na influx and the development of cardiac actions of ouabain were studied at 30 and 37°C in isolated left atrial muscle of guinea pig heart. At 30°C, the developxnent of the positive inotropic action of 0.3 uM ouabain was significantly slower and more dependent on the stimulation frecguency between 0.5 to 3 He, than in corresponding studies performed at 37%. The development of contracture produced by 5 uM ouabain was also markedly slower at 30°C than at 37%. Na+ influx@te+ was estimated indirectly from the specific (ouabain-sensitive) K uptakf by left atrial muscle preparations which were not prelopded with thes+e preparations are the steady sta& t+h” Na efflux is Eda . When equal to the Na influx, and hence the specific $ uptake represents the ongoing @ i%m pump activity and also Ma influx rate. At 36%, the specific K uptake of quiescent muscle was low and was enhanced by electrical stimulation. ar$edly At 37’C, the specific zi K uptake of the quiescent muscle was approximately twice the value observed at 3@C, and relative increase in the uptake caused by electr@al stimulation was substantially smaller. Thus, the variations in Na influx rates can account for the differences in rates of development of the cardiac actions of ouabain when temperature and stimulation frequency are altered. (Supported by USPHS grant I-IL-16052 from the MHLBI.)

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