A comparison of nucleoside transport and metabolism in hypertensive and normotensive rats.
In a previous study, we discovered that spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) are dissimilar with respect to the depressor potency differentiated between intravenously and intra-arterially infused adenosine. To test the hypothesis that this dissimilarity may reflect a difference between the two strains in adenosine transport or metabolism, we compared the kinetics of nucleoside transport (i.e., [3H]uridine uptake) in erythrocytes and the pulmonary disposition of [3H]adenosine in SHR versus WKY. [3H]Uridine uptake in rat erythrocytes was linear for 4 minutes and inhibitable with dipyridamole. Kinetic analysis (i.e., Hofstee plots) of initial uptake velocity indicated no difference between the two strains with respect to apparent Km (196 +/- 40 vs 230 +/- 29 microM in WKY and SHR, respectively) and maximum velocity (7.5 +/- 0.4 vs 8.3 +/- 0.5 pmol/2 min/12% Hct in WKY and SHR, respectively). Approximately 50% of [3H]adenosine infused into the pulmonary artery of perfused rat lung was transported into the lung, and 85% of this material was incorporated into the nucleotide pool. Radioactivity in the lung perfusate consisted initially of equal amounts of adenosine and inosine; however, within 60 seconds after administration of [3H]adenosine most of the effluent radioactivity was inosine. No differences were detected in adenosine uptake, intracellular metabolism, or extracellular metabolism in lung from SHR versus WKY. Our data indicate that any difference between SHR and WKY with respect to the biological response to adenosine cannot be attributed to differences in adenosine disposition and, therefore, must be due to pharmacodynamic differences between the strains.
Bottiglieri
D F
DF
Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232.
Robertson
D
D
Jackson
E K
EK
D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D001794:Blood Pressure / Q000187:drug effects; D004912:Erythrocytes / Q000378:metabolism; D006973:Hypertension / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000378:metabolism; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014316:Tritium
D014316:Tritium; D000241:Adenosine