p.43 INCREASED CARDIAC RESPONSE TO ADRENERGIC STIMULATION AND INCREASED B-RECEPTOR AGONIST AFFINITY IN MALNOURISHED RATS. C.Drott, L. Ransnas, B. Jacobsson, A. Hjalmarson & K. Lundholm. Departments of Surgery I and Medicine I, Sahlgrenska Hospital, Gothenburg, Sweden. Aim: To evaluate the cardiac adrenergic adaptation in malnutrition. Methods: Growing Sprague-Dawley rats were starved during 4 days or given a protein free diet during 2'weeks. These malnourished rats were compared to freely-fed controls by experiments performed in an isolated working heart preparation. Isoproterenol and norepinephrine respectively were added to the perfusate at increasing cont. and the physiological cardiac response was recorded. In addition, the B-receptor agonist affinity was studied in isolated cell membrane preparations using ICYP/Isoproterenol competition binding. Finally ATPase activity was measured in purified myosin preparations. Results: Malnourished rats lost significant amounts of myocardial mass but the heart pumping ability was maintained in spite of this. Malnutrition was associated with an increased sensitivity and responsiveness to Isoproterenol and norepinephrine measured as left ventricular peak systolic pressure, contractility (dP/dt) and heart rate. The number of B-receptors were not different between groups but myocardial membranes derived from malnourished rats exhibited a more than 10 fold increase in the affinity for Isoproterenol binding. ATPase activity in purified myosin preparations was unexpectedly lower in malnourished rats compared to freely-fed controls. Conclusion: Increased cardiac sensitivity and responsiveness to adrenergic stimulation is a means by which malnourished subjects can functionally circumvent cardiac insufficiency otherwise associated with malnutrition.
PA4
ADAPMvE-
m
APICAI,ANDBASOLATE~AI,ACIDTRANSPORTINJEJI~OFRATSFED Dept of Physiology, M.J. Rennie.
LOW (8%) PROTEIN DIFT. C.J.&an, P.M.Taylor, University, Dundee, DDl 4HN, Scotland.
mee
Acutely feeding rats a 1~ (8%) protein diet (IPD), results (14d) in adaptationof the jejunal mucosa including 50% increases in wet weight, villus height, tissue protein and DNA. Although little is kncwn about the controllingmechanisms,an increase in the fractionalprotein syntheticrate (from 130 to 165%/d) must be an important factor. The amino acids supplying the pcol for protein synthesis could originate fran the blood (ie basolateral)or lumen (ie apical) sides and the adaptive increase in the protein synthetic rate may be acccmpanied by an increase in the uptake of amino acids frcxn either. We have investigatedthese possibilities.Basolateralamino acid transport was studied using the paired tracer dilution technique in an isolateddually perfused jejunum preparation,using 14C-sucrose (extracellularmarker) and 3H-transportableamino acids in the vascular perfusate at physiological concentrations.Net uptake across the apical membrane was studied on other rats using 3H-prolineand 14C-phenylalaninein the luminal perfusate at 0-20&l concentrations.Results fran 5 rats on LPD, canpared to those fran rats fed a normal (24%) protein diet, shawed increased influx of trace GLU, PRO, GLY and PHE across the basolateralmembrane by 900, 106, 97 and 45% respectively(fran 0.8~0.4; 16~2.7; 41k5.5 and 11&0.6 nmol/min/gx;tsE,n=3). (Therewere no changes in flux of ALA, LEU or LYS). Net absorptionof PHE and PRO fran the apical side also increasedat a, all concentrationsin rats fed LPD. PIE uptake was saturatedat concentrationsabove 5mM; uptake at 5-20mM increased frcm 134214 (control)to 271236 (LPD) nmol/min/g (x$GE, n=12). Kinetic characteristicsof transportwere also changed. Capacity for amino acid uptake (VInax)was significantlyincreased (p